A systematic survey of LU domain-containing proteins reveals a novel human gene, <i>LY6A</i>, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

doi:10.1007/s11684-022-0968-4

Front. Med.

2023, Vol. 17

Issue (3) : 458-475 https://doi.org/10.1007/s11684-022-0968-4

RESEARCH ARTICLE

A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

Dan Liu^1,², Chunhui Xu³, Yanting Liu⁴, Wen Ouyang¹, Shaojian Lin⁴, Aining Xu¹, Yuanliang Zhang¹, Yinyin Xie¹, Qiuhua Huang¹, Weili Zhao¹, Zhu Chen¹, Lan Wang³, Saijuan Chen¹(

), Jinyan Huang^1,⁵(

), Zhe Bao Wu^4,⁶(

), Xiaojian Sun¹(

)

¹. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
². Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China
³. CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
⁴. Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
⁵. Biomedical Big Data Center, First Affiliated Hospital, Zhejiang University School of Medicine, and Cancer Center, Zhejiang University, Hangzhou 310000, China
⁶. Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China

Download: PDF(11888 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon‒intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

Keywords LU domain-containing protein family novel human gene LY6A pituitary tumor biomarker nonsynonymous SNP GPI-anchored protein

Corresponding Author(s): Saijuan Chen,Jinyan Huang,Zhe Bao Wu,Xiaojian Sun

Just Accepted Date: 03 February 2023 Online First Date: 15 March 2023 Issue Date: 28 July 2023

Cite this article:

Dan Liu,Chunhui Xu,Yanting Liu, et al. A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors[J]. Front. Med., 2023, 17(3): 458-475.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-022-0968-4
https://academic.hep.com.cn/fmd/EN/Y2023/V17/I3/458

Species	Gene symbol	Full gene name	Protein accession number	Number of LU domains
Human	ACRV1	Acrosomal vesicle protein 1	NP_001603.1	1
Human	CD177	CD177 molecule	NP_065139.2	4
Human	CD59	CD59 molecule (CD59 blood group)	NP_976075.1	1
Human	GML	Glycosylphosphatidylinositol anchored molecule like	NP_002057.1	1
Human	GPIHBP1	Glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1	NP_835466.2	1
Human	LY6A	Lymphocyte antigen 6 family member A	WBG67602.1	1
Human	LY6D	Lymphocyte antigen 6 family member D	NP_003686.1	1
Human	LY6E	Lymphocyte antigen 6 family member E	NP_002337.1	1
Human	LY6G5B	Lymphocyte antigen 6 family member G5B	NP_067044.2	1
Human	LY6G5C	Lymphocyte antigen 6 family member G5C	NP_079538.3	1
Human	LY6G6C	Lymphocyte antigen 6 family member G6C	NP_079537.1	1
Human	LY6G6D	Lymphocyte antigen 6 family member G6D	NP_067069.2	1
Human	LY6G6E	Lymphocyte antigen 6 family member G6E	CAB52193.1	1
Human	LY6G6F	Lymphocyte antigen 6 family member G6F	NP_001003693.1	1
Human	LY6H	Lymphocyte antigen 6 family member H	NP_002338.3	1
Human	LY6K	Lymphocyte antigen 6 family member K	NP_059997.3	1
Human	LY6L	Lymphocyte antigen 6 family member L	NP_001355089.1	1
Human	LYNX1	Ly6/neurotoxin 1	NP_803430.1	1
Human	LYPD1	LY6/PLAUR domain containing 1	NP_653187.3	1
Human	LYPD2	LY6/PLAUR domain containing 2	NP_991108.1	1
Human	LYPD3	LY6/PLAUR domain containing 3	NP_055215.2	2
Human	LYPD4	LY6/PLAUR domain containing 4	NP_775777.3	2
Human	LYPD5	LY6/PLAUR domain containing 5	NP_001026919.2	2
Human	LYPD6	LY6/PLAUR domain containing 6	NP_001182614.1	1
Human	LYPD6B	LY6/PLAUR domain containing 6B	NP_001303931.1	1
Human	LYPD8	LY6/PLAUR domain containing 8	NP_001078943.2	2
Human	PATE1	Prostate and testis expressed 1	NP_612151.1	1
Human	PATE2	Prostate and testis expressed 2	NP_997720.1	1
Human	PATE3	Prostate and testis expressed 3	NP_001123355.3	1
Human	PATE4	Prostate and testis expressed 4	NP_001138346.1	1
Human	PINLYP	Phospholipase A2 inhibitor and LY6/PLAUR domain containing	NP_001180550.2	2
Human	PLAUR	Plasminogen activator, urokinase receptor	NP_002650.1	3
Human	PSCA	Prostate stem cell antigen	NP_005663.2	1
Human	SLURP1	Secreted LY6/PLAUR domain containing 1	NP_065160.1	1
Human	SLURP2	Secreted LY6/PLAUR domain containing 2	NP_803253.1	1
Human	SPACA4	Sperm acrosome associated 4	NP_598005.1	1
Human	TEX101	Testis expressed 101	NP_113639.4	2
Mouse	1810065E05Rik	RIKEN cDNA 1810065E05 gene	NP_081515.2	2
Mouse	Acrv1	Acrosomal vesicle protein 1	NP_031417.2	1
Mouse	Cd177	CD177 antigen	NP_081138.2	8
Mouse	Cd59a	CD59a antigen	NP_001104530.1	1
Mouse	Cd59b	CD59b antigen	NP_862906.1	1
Mouse	Gm34531	Predicted gene, 34531	NP_001371170.1	1
Mouse	Gml	Glycosylphosphatidylinositol anchored molecule like	NP_001170995.1	1
Mouse	Gml2	Glycosylphosphatidylinositol anchored molecule like 2	NP_034546.2	1
Mouse	Gpihbp1	GPI-anchored HDL-binding protein 1	NP_081006.1	1
Mouse	Ly6a	Lymphocyte antigen 6 complex, locus A	NP_001258345.1	1
Mouse	Ly6a2	Lymphocyte antigen 6 complex, locus A2	NP_001365169.1	1
Mouse	Ly6c1	Lymphocyte antigen 6 complex, locus C1	NP_034871.2	1
Mouse	Ly6c2	Lymphocyte antigen 6 complex, locus C2	NP_001092687.1	1
Mouse	Ly6d	Lymphocyte antigen 6 complex, locus D	NP_034872.1	1
Mouse	Ly6e	Lymphocyte antigen 6 complex, locus E	NP_001157508.2	1
Mouse	Ly6f	Lymphocyte antigen 6 complex, locus F	NP_032556.1	1
Mouse	Ly6g	Lymphocyte antigen 6 complex, locus G	NP_001297367.1	1
Mouse	Ly6g2	Lymphocyte antigen 6 complex, locus G2	NP_001358034.1	1
Mouse	Ly6g5b	Lymphocyte antigen 6 complex, locus G5B	NP_683741.1	1
Mouse	Ly6g5c	Lymphocyte antigen 6 complex, locus G5C	NP_683749.1	1
Mouse	Ly6g6c	Lymphocyte antigen 6 complex, locus G6C	NP_075952.1	1
Mouse	Ly6g6d	Lymphocyte antigen 6 complex, locus G6D	NP_258439.1	1
Mouse	Ly6g6e	Lymphocyte antigen 6 complex, locus G6E	NP_081642.1	1
Mouse	Ly6g6f	Lymphocyte antigen 6 complex, locus G6F	NP_001156664.1	1
Mouse	Ly6g6g	Lymphocyte antigen 6 complex, locus G6G	NP_001371082.1	1
Mouse	Ly6h	Lymphocyte antigen 6 complex, locus H	NP_035967.1	1
Mouse	Ly6i	Lymphocyte antigen 6 complex, locus I	NP_065244.2	1
Mouse	Ly6k	Lymphocyte antigen 6 complex, locus K	NP_083903.1	1
Mouse	Ly6l	Lymphocyte antigen 6 complex, locus L	NP_001333978.1	1
Mouse	Ly6m	Lymphocyte antigen 6 complex, locus M	NP_080205.1	1
Mouse	Lynx1	Ly6/neurotoxin 1	NP_035968.1	1
Mouse	Lypd1	Ly6/Plaur domain containing 1	NP_659568.2	1
Mouse	Lypd2	Ly6/Plaur domain containing 2	NP_080947.1	1
Mouse	Lypd3	Ly6/Plaur domain containing 3	NP_598504.1	2
Mouse	Lypd4	Ly6/Plaur domain containing 4	NP_877586.1	2
Mouse	Lypd5	Ly6/Plaur domain containing 5	NP_084082.1	2
Mouse	Lypd6	LY6/PLAUR domain containing 6	NP_796113.1	1
Mouse	Lypd6b	LY6/PLAUR domain containing 6B	NP_001366310.1	1
Mouse	Lypd8	LY6/PLAUR domain containing 8	NP_001077353.1	2
Mouse	Lypd8l	LY6/PLAUR domain containing 8 like	NP_653127.2	2
Mouse	Lypd9	LY6/PLAUR domain containing 9	NP_997410.1	1
Mouse	Lypd10	Ly6/PLAUR domain containing 10	NP_954601.1	2
Mouse	Lypd11	Ly6/PLAUR domain containing 11	NP_808261.1	1
Mouse	Pate1	Prostate and testis expressed 1	NP_001186882.1	1
Mouse	Pate2	Prostate and testis expressed 2	NP_001028593.1	1
Mouse	Pate3	Prostate and testis expressed 3	NP_001161064.1	1
Mouse	Pate4	Prostate and testis expressed 4	NP_064660.2	1
Mouse	Pate5	Prostate and testis expressed 5	NP_084139.1	1
Mouse	Pate6	Prostate and testis expressed 6	NP_080869.1	1
Mouse	Pate7	Prostate and testis expressed 7	NP_001161145.1	1
Mouse	Pate8	Prostate and testis expressed 8	NP_001161056.1	1
Mouse	Pate9	Prostate and testis expressed 9	NP_001028955.1	1
Mouse	Pate10	Prostate and testis expressed 10	NP_001161060.1	1
Mouse	Pate11	Prostate and testis expressed 11	NP_001121982.1	1
Mouse	Pate12	Prostate and testis expressed 12	NP_001161058.1	1
Mouse	Pate13	Prostate and testis expressed 13	NP_001365151.1	1
Mouse	Pate14	Prostate and testis expressed 14	NP_001028497.1	1
Mouse	Pinlyp	Phospholipase A2 inhibitor and LY6/PLAUR domain containing	NP_001032220.1	2
Mouse	Plaur	Plasminogen activator, urokinase receptor	NP_035243.1	3
Mouse	Psca	Prostate stem cell antigen	NP_082492.1	1
Mouse	Slurp1	Secreted Ly6/Plaur domain containing 1	NP_065265.1	1
Mouse	Slurp2	Secreted Ly6/Plaur domain containing 2	NP_001075430.1	1
Mouse	Spaca4	Sperm acrosome associated 4	NP_081331.2	1
Mouse	Tex101	Testis expressed gene 101	NP_064365.1	2

Tab.1 Human and mouse LU domain-containing genes and the numbers of LU domains

Fig.1 Systematic survey of LU domain-containing proteins in humans and mice. (A) Representative homology analysis between mouse (Mm) and human (Hs) CD177 proteins. Note that these two protein sequences formed multiple, nonlinear alignment patterns, indicating complicated arrangements of multiple homologous regions in these proteins. Blue and red vertical lines denote inserted and mismatched residues, respectively. This analysis was performed with the NCBI blast program and visualized by the Multiple Sequence Alignment (MSA) viewer. (B) Domain architectures of mouse and human CD177 proteins, which contain 8 and 4 LU domains, respectively. The N-terminal signal peptide (SP) and the C-terminal GPI anchor domain (GPIa) are also illustrated. (C) Multisequence alignment of all human and mouse LU domains identified in annotated proteins, although many of the LU domains were previously unannotated. Several of the most conserved amino acids are highlighted. These LU domains are numbered from the N-terminus to C-terminus out of the total number of LU domains of the gene (e.g., 2/8 means the 2nd out of the 8 LU domains in the whole protein). (D) Phylogenetic tree of all human and mouse LU domains constructed based on multisequence alignment. Note that, although most of the orthologous genes (or groups of genes) are shared by humans and mice, the mouse Ly6a cluster (covered by the blue curve) seems not to have a human orthologous gene/group.

Fig.2 Comparative genomic analysis identifying the human LY6A gene, which is located within the C8orf31 gene locus but transcribed from the opposite strand. (A) Synteny analysis between the human chromosome (Hs Chr) 8q24.3 and the mouse chromosome (Mm Chr) 15qD3 regions, showing that the mouse Ly6a cluster, although having no annotated human ortholog, is homologous to the human genomic region that encompasses the C8orf31 gene. (B) Bioinformatic approach workflow to search and validate the potential human ortholog(s) of mouse Ly6a. (C) Alignment results of the “tblastn” search, indicating that three human genomic regions (potential exons) can be matched to the query (mouse Ly-6A/Sca-1 protein) sequence. Note that two of these aligned regions likely belong to the same gene (putative gene #1), because they cover successive regions in the query sequence and the matched genomic sequences can be predicted as two adjacent exons, whereas the third aligned region largely overlaps with the first one in the query sequence and, therefore, it likely represents a separate gene (putative gene #2). The arrows denote the 10 characteristic cysteines within the LU domain, most of which (red) are conserved in human LY6A, and a few (blue) are not. (D) Representative RNA-seq reads that show considerable sequence similarities but are actually transcribed from different genes. The top panels show the sequence alignments of two pairs of RNA-seq reads, and the lower panels show the mapping of the reads to the human genomic sequence. Note that the splice donor and acceptor sites (red) on the opposite strands clearly indicate that these reads are transcribed in opposite directions and thus represent different genes (i.e., C8orf31 or LY6A). Accordingly, specific PCR primers for detecting different genes can only be designed in these very limited, unmatched regions in the top panels. (E) Validated exon/intron structure and alternative splice patterns of the human LY6A gene aligned with those of C8orf31 in the opposite direction. These results were based on the RNA-seq analysis of a single pituitary tumor sample.

Fig.3 Full-length cloning, interferon induction, and gene expression profiling of LY6A. (A) RT-PCR amplification of a LY6A-specific fragment from two AML cell lines and two pituitary tumor samples. (B) IFN-γ upregulates LY6A expression in pituitary tumor cells. (C) Sequencing results of the RT-PCR amplicon from pituitary tumor patient #2, showing the regions surrounding the splice junction sites. Deduced amino acid sequences are written beneath. (D) Analyses of the ENCODE and GTEx RNA-seq data, showing LY6A mRNA expression in different human tissues. LY6A expression levels are indicated by the counts of its splicing junction sites (i.e., exons 1–2 and 2–3) normalized to millions of mapped reads (CPM) of each sample. Note that both profiles show relatively higher LY6A expression in the spleen and testis, whereas the ENCODE profile shows a particularly high level in adipose tissue, which is probably due to the different subtypes of adipose tissue used in these projects. (E) Expression patterns of the currently known human Ly-6 family genes. Data were obtained from the GTEx project. The expression values are shown as transcripts per million (TPM) based on the RNA-seq analysis of multiple human tissues. (F) RT-PCR analysis of LY6A mRNA expression in collected human tissues. (G) Analysis of LY6A expression in the data set [43] that contains the multiple RNA-seq results of total RNA, polyA RNA, and small RNA of spleen tissue, splenic endothelial cells, and splenic fibroblasts.

Fig.4 Gene expression profiling of five pituitary tumor samples from patients with Cushing’s disease. (A) Relatively high and low LY6A mRNA expression levels in the tumor samples as indicated by CPM in their RNA-seq raw data. (B) Gene set enrichment analysis of the RNA-seq data, showing four examples of the substantially enriched gene sets in the analysis of high-LY6A versus low-LY6A tumor samples. (C) Unsupervised hierarchical clusters of the five tumor samples and the genes in the same gene sets shown in panel (B). The genes undetectable in the samples are colored in gray. Note that the low- and high-LY6Atumor samples can be clustered into separate groups by their differential gene expression.

Fig.5 Evolutionary conservation of the LY6A-encoded protein and identification of a high-frequency nonsynonymous coding SNP. (A) Multiple alignment of the full-length protein sequences of the Ly6a and Ly6l subfamily members. The asterisk, colon, and period under the aligned sequences denote fully, strongly, and weakly conserved amino acids, respectively. The red and blue arrows denote the conserved and nonconserved cysteines, respectively, in human LY6A. The orange arrow denotes the C-to-T nucleotide variation that causes a G-to-S amino acid change and is therefore defined as a nonsynonymous coding SNP. All these sequences are encoded by three exons (ORF-exon 1–3) with well-aligned splice junction sites as labeled by the square brackets on the top of the alignment. The signal peptide and the GPIa domain exist in all these proteins as labeled by the square brackets below the alignment, and they can be clearly recognized by computational programs, such as SignalP and PredGPI. (B) Phylogenetic relationship of human LY6A with mouse Ly6a cluster genes. The Ly6l subfamily, which is the closest homolog of the Ly6a cluster, was used as the outgroup. (C) Frequencies of the “G” and “S” alleles of LY6A in the indicated population studies. Data are derived from dbSNP.

Fig.6 Proper expression, processing, and membrane tethering of the LY6A protein. (A) Experimental design, showing the domain architectures of the human LY6A (hLY6A) and mouse Ly-6A (mLy-6A) proteins inserted with a 3×FLAG tag (F) and a HaloTag (Halo) for detecting total protein and membrane tethering, respectively, and a summary of the experimental results. (B) Fluorescent signals of the HaloTag ligand and the immunoblot signals of the 3×FLAG tag. β-actin is shown as the loading control. (C) Immunoblot analysis of the monoclonal stable cell lines that express the empty vector (F:Halo tag) and the tagged hLY6A and mLy-6A proteins. (D) Cell viability analysis of the 15 monoclonal stable cell lines shown in panel C. Note that the hLY6A cell lines exhibited slightly increased proliferation compared with the vector control cell lines (P < 0.05 at 96 h, two-tailed t test), whereas the mLy-6A cell lines did not show this trend. Data are presented as mean ± SD of the five monoclonal stable cell lines (growing in duplicated wells) for each group.

1	AJ Feeney, U Hämmerling. Ala-1: a murine alloantigen of activated lymphocytes. Immunogenetics 1976; 3(1): 369–379 https://doi.org/10.1007/BF01576968
2	JN Woody, M Feldmann, PC Beverley, IF McKenzie. Expression of alloantigens LY-5 and LY-6 on cytotoxic effector cells. J Immunol 1977; 118(5): 1739–1743 https://doi.org/10.4049/jimmunol.118.5.1739 pmid: 323358
3	EA Boyse, LJ Old. Some aspects of normal and abnormal cell surface genetics. Annu Rev Genet 1969; 3(1): 269–290 https://doi.org/10.1146/annurev.ge.03.120169.001413
4	BA Houlden, PM Hogarth, IF McKenzie. Interrelationships of the “Ly-6 complex” antigens. Immunogenetics 1986; 23(4): 226–232 https://doi.org/10.1007/BF00373017 pmid: 2422115
5	KP LeClair, RG Palfree, PM Flood, U Hammerling, A Bothwell. Isolation of a murine Ly-6 cDNA reveals a new multigene family. EMBO J 1986; 5(12): 3227–3234 https://doi.org/10.1002/j.1460-2075.1986.tb04633.x pmid: 3028776
6	CL Loughner, EA Bruford, MS McAndrews, EE Delp, S Swamynathan, SK Swamynathan. Organization, evolution and functions of the human and mouse Ly6/uPAR family genes. Hum Genomics 2016; 10(1): 10 https://doi.org/10.1186/s40246-016-0074-2 pmid: 27098205
7	TP Gumley, IF McKenzie, MS Sandrin. Tissue expression, structure and function of the murine Ly-6 family of molecules. Immunol Cell Biol 1995; 73(4): 277–296 https://doi.org/10.1038/icb.1995.45 pmid: 7493764
8	H Reiser, H Oettgen, ET Yeh, C Terhorst, MG Low, B Benacerraf, KL Rock. Structural characterization of the TAP molecule: a phosphatidylinositol-linked glycoprotein distinct from the T cell receptor/T3 complex and Thy-1. Cell 1986; 47(3): 365–370 https://doi.org/10.1016/0092-8674(86)90593-3 pmid: 2876780
9	GJ Spangrude, S Heimfeld, IL Weissman. Purification and characterization of mouse hematopoietic stem cells. Science 1988; 241(4861): 58–62 https://doi.org/10.1126/science.2898810 pmid: 2898810
10	BE Welm, SB Tepera, T Venezia, TA Graubert, JM Rosen, MA Goodell. Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Dev Biol 2002; 245(1): 42–56 https://doi.org/10.1006/dbio.2002.0625 pmid: 11969254
11	L Xin, DA Lawson, ON Witte. The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proc Natl Acad Sci USA 2005; 102(19): 6942–6947 https://doi.org/10.1073/pnas.0502320102 pmid: 15860580
12	CF Kim, EL Jackson, AE Woolfenden, S Lawrence, I Babar, S Vogel, D Crowley, RT Bronson, T Jacks. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005; 121(6): 823–835 https://doi.org/10.1016/j.cell.2005.03.032 pmid: 15960971
13	C Holmes, WL Stanford. Concise review: stem cell antigen-1: expression, function, and enigma. Stem Cells 2007; 25(6): 1339–1347 https://doi.org/10.1634/stemcells.2006-0644 pmid: 17379763
14	WL Stanford, S Haque, R Alexander, X Liu, AM Latour, HR Snodgrass, BH Koller, PM Flood. Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) null mice. J Exp Med 1997; 186(5): 705–717 https://doi.org/10.1084/jem.186.5.705 pmid: 9271586
15	P Hanson, V Mathews, SH Marrus, TA Graubert. Enhanced green fluorescent protein targeted to the Sca-1 (Ly-6A) locus in transgenic mice results in efficient marking of hematopoietic stem cells in vivo. Exp Hematol 2003; 31(2): 159–167 https://doi.org/10.1016/S0301-472X(02)01021-4 pmid: 12591281
16	CY Ito, CY Li, A Bernstein, JE Dick, WL Stanford. Hematopoietic stem cell and progenitor defects in Sca-1/Ly-6A-null mice. Blood 2003; 101(2): 517–523 https://doi.org/10.1182/blood-2002-06-1918 pmid: 12393491
17	SB Bradfute, TA Graubert, MA Goodell. Roles of Sca-1 in hematopoietic stem/progenitor cell function. Exp Hematol 2005; 33(7): 836–843 https://doi.org/10.1016/j.exphem.2005.04.001 pmid: 15963860
18	JK Whitmire, B Eam, JL Whitton. Mice deficient in stem cell antigen-1 (Sca1, Ly-6A/E) develop normal primary and memory CD4+ and CD8+ T-cell responses to virus infection. Eur J Immunol 2009; 39(6): 1494–1504 https://doi.org/10.1002/eji.200838959 pmid: 19384870
19	ZX Zhang, WL Stanford, L Zhang. Ly-6A is critical for the function of double negative regulatory T cells. Eur J Immunol 2002; 32(6): 1584–1592 https://doi.org/10.1002/1521-4141(200206)32:6<1584::AID-IMMU1584>3.0.CO;2-2 pmid: 12115641
20	MA Jones, S DeWolf, V Vacharathit, M Yim, S Spencer, AK Bamezai. Investigating B cell development, natural and primary antibody responses in Ly-6A/Sca-1 deficient mice. PLoS One 2016; 11(6): e0157271 https://doi.org/10.1371/journal.pone.0157271 pmid: 27322740
21	M Bonyadi, SD Waldman, D Liu, JE Aubin, MD Grynpas, WL Stanford. Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice. Proc Natl Acad Sci USA 2003; 100(10): 5840–5845 https://doi.org/10.1073/pnas.1036475100 pmid: 12732718
22	PO Mitchell, T Mills, RS O’Connor, ER Kline, T Graubert, E Dzierzak, GK Pavlath. Sca-1 negatively regulates proliferation and differentiation of muscle cells. Dev Biol 2005; 283(1): 240–252 https://doi.org/10.1016/j.ydbio.2005.04.016 pmid: 15901485
23	CL Epting, JE López, A Pedersen, C Brown, P Spitz, PC Ursell, HS Bernstein. Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of alpha7 integrin-expressing myoblasts. Exp Cell Res 2008; 314(5): 1125–1135 https://doi.org/10.1016/j.yexcr.2007.11.010 pmid: 18073129
24	G Upadhyay, Y Yin, H Yuan, X Li, R Derynck, RI Glazer. Stem cell antigen-1 enhances tumorigenicity by disruption of growth differentiation factor-10 (GDF10)-dependent TGF-β signaling. Proc Natl Acad Sci USA 2011; 108(19): 7820–7825 https://doi.org/10.1073/pnas.1103441108 pmid: 21518866
25	KK Long, M Montano, GK Pavlath. Sca-1 is negatively regulated by TGF-β1 in myogenic cells. FASEB J 2011; 25(4): 1156–1165 https://doi.org/10.1096/fj.10-170308 pmid: 21156809
26	HD Song, XJ Sun, M Deng, GW Zhang, Y Zhou, XY Wu, Y Sheng, Y Chen, Z Ruan, CL Jiang, HY Fan, LI Zon, JP Kanki, TX Liu, AT Look, Z Chen. Hematopoietic gene expression profile in zebrafish kidney marrow. Proc Natl Acad Sci USA 2004; 101(46): 16240–16245 https://doi.org/10.1073/pnas.0407241101 pmid: 15520368
27	XJ Sun, PF Xu, T Zhou, M Hu, CT Fu, Y Zhang, Y Jin, Y Chen, SJ Chen, QH Huang, TX Liu, Z Chen. Genome-wide survey and developmental expression mapping of zebrafish SET domain-containing genes. PLoS One 2008; 3(1): e1499 https://doi.org/10.1371/journal.pone.0001499 pmid: 18231586
28	C Burge, S Karlin. Prediction of complete gene structures in human genomic DNA. J Mol Biol 1997; 268(1): 78–94 https://doi.org/10.1006/jmbi.1997.0951 pmid: 9149143
29	MA Larkin, G Blackshields, NP Brown, R Chenna, PA McGettigan, H McWilliam, F Valentin, IM Wallace, A Wilm, R Lopez, JD Thompson, TJ Gibson, DG Higgins. Clustal W and Clustal X version 2.0. Bioinformatics 2007; 23(21): 2947–2948 https://doi.org/10.1093/bioinformatics/btm404 pmid: 17846036
30	K Tamura, G Stecher, D Peterson, A Filipski, S Kumar. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol 2013; 30(12): 2725–2729 https://doi.org/10.1093/molbev/mst197 pmid: 24132122
31	H Yao, W Xie, Y Dai, Y Liu, W Gu, J Li, L Wu, J Xie, W Rui, B Ren, L Xue, Y Cheng, S Lin, C Li, H Tang, Y Wang, M Lou, X Zhang, R Hu, H Shang, J Huang, ZB Wu. TRIM65 determines the fate of a novel subtype of pituitary neuroendocrine tumors via ubiquitination and degradation of TPIT. Neuro-oncol 2022; 24(8): 1286–1297 https://doi.org/10.1093/neuonc/noac053 pmid: 35218667
32	XJ Sun, Z Wang, L Wang, Y Jiang, N Kost, TD Soong, WY Chen, Z Tang, T Nakadai, O Elemento, W Fischle, A Melnick, DJ Patel, SD Nimer, RG Roeder. A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis. Nature 2013; 500(7460): 93–97 https://doi.org/10.1038/nature12287 pmid: 23812588
33	N Liu, J Song, Y Xie, XL Wang, B Rong, N Man, MM Zhang, Q Zhang, FF Gao, MR Du, Y Zhang, J Shen, CH Xu, CL Hu, JC Wu, P Liu, YL Zhang, YY Xie, P Liu, JY Huang, QH Huang, F Lan, S Shen, SD Nimer, Z Chen, SJ Chen, RG Roeder, L Wang, XJ Sun. Different roles of E proteins in t(8;21) leukemia: E2-2 compromises the function of AETFC and negatively regulates leukemogenesis. Proc Natl Acad Sci USA 2019; 116(3): 890–899 https://doi.org/10.1073/pnas.1809327116 pmid: 30593567
34	MM Zhang, N Liu, YL Zhang, B Rong, XL Wang, CH Xu, YY Xie, S Shen, J Zhu, SD Nimer, Z Chen, SJ Chen, RG Roeder, F Lan, L Wang, QH Huang, XJ Sun. Destabilization of AETFC through C/EBPα-mediated repression of LYL1 contributes to t(8;21) leukemic cell differentiation. Leukemia 2019; 33(7): 1822–1827 https://doi.org/10.1038/s41375-019-0398-8 pmid: 30755707
35	YF Zhang, XL Wang, CH Xu, N Liu, L Zhang, YM Zhang, YY Xie, YL Zhang, QH Huang, L Wang, Z Chen, SJ Chen, RG Roeder, S Shen, K Xue, XJ Sun. A direct comparison between AML1-ETO and ETO2-GLIS2 leukemia fusion proteins reveals context-dependent binding and regulation of target genes and opposite functions in cell differentiation. Front Cell Dev Biol 2022; 10: 992714 https://doi.org/10.3389/fcell.2022.992714 pmid: 36158200
36	F Zhang, QY Zeng, H Xu, AN Xu, DJ Liu, NZ Li, Y Chen, Y Jin, CH Xu, CZ Feng, YL Zhang, D Liu, N Liu, YY Xie, SH Yu, H Yuan, K Xue, JY Shi, TX Liu, PF Xu, WL Zhao, Y Zhou, L Wang, QH Huang, Z Chen, SJ Chen, XL Zhou, XJ Sun. Selective and competitive functions of the AAR and UPR pathways in stress-induced angiogenesis. Cell Discov 2021; 7(1): 98 https://doi.org/10.1038/s41421-021-00332-8 pmid: 34697290
37	JL Rinn, HY Chang. Genome regulation by long noncoding RNAs. Annu Rev Biochem 2012; 81(1): 145–166 https://doi.org/10.1146/annurev-biochem-051410-092902 pmid: 22663078
38	EV Koonin. Orthologs, paralogs, and evolutionary genomics. Annu Rev Genet 2005; 39(1): 309–338 https://doi.org/10.1146/annurev.genet.39.073003.114725 pmid: 16285863
39	FJ Dumont, LZ Coker. Interferon-α/β enhances the expression of Ly-6 antigens on T cells in vivo and in vitro. Eur J Immunol 1986; 16(7): 735–740 https://doi.org/10.1002/eji.1830160704 pmid: 3487457
40	FJ Dumont, RC Boltz. The augmentation of surface Ly-6A/E molecules in activated T cells is mediated by endogenous interferon-gamma. J Immunol 1987; 139(12): 4088–4095 https://doi.org/10.4049/jimmunol.139.12.4088 pmid: 3121727
41	Y Luo, BC Hitz, I Gabdank, JA Hilton, MS Kagda, B Lam, Z Myers, P Sud, J Jou, K Lin, UK Baymuradov, K Graham, C Litton, SR Miyasato, JS Strattan, O Jolanki, JW Lee, FY Tanaka, P Adenekan, E O’Neill, JM Cherry. New developments on the Encyclopedia of DNA Elements (ENCODE) data portal. Nucleic Acids Res 2020; 48(D1): D882–D889 https://doi.org/10.1093/nar/gkz1062 pmid: 31713622
42	Consortium GTEx. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 2020; 369(6509): 1318–1330 https://doi.org/10.1126/science.aaz1776 pmid: 32913098
43	L Lorenzi, HS Chiu, F Avila Cobos, S Gross, PJ Volders, R Cannoodt, J Nuytens, K Vanderheyden, J Anckaert, S Lefever, AP Tay, EJ de Bony, W Trypsteen, F Gysens, M Vromman, T Goovaerts, TB Hansen, S Kuersten, N Nijs, T Taghon, K Vermaelen, KR Bracke, Y Saeys, T De Meyer, NP Deshpande, G Anande, TW Chen, MR Wilkins, A Unnikrishnan, K De Preter, J Kjems, J Koster, GP Schroth, J Vandesompele, P Sumazin, P Mestdagh. The RNA Atlas expands the catalog of human non-coding RNAs. Nat Biotechnol 2021; 39(11): 1453–1465 https://doi.org/10.1038/s41587-021-00936-1 pmid: 34140680
44	I Donangelo, SG Ren, T Eigler, C Svendsen, S Melmed. Sca1+ murine pituitary adenoma cells show tumor-growth advantage. Endocr Relat Cancer 2014; 21(2): 203–216 https://doi.org/10.1530/ERC-13-0229 pmid: 24481638
45	ES Lander, LM Linton, B Birren, C Nusbaum, MC Zody, J Baldwin, K Devon, K Dewar, M Doyle, W FitzHugh, R Funke, D Gage, K Harris, A Heaford, J Howland, L Kann, J Lehoczky, R LeVine, P McEwan, K McKernan, J Meldrim, JP Mesirov, C Miranda, W Morris, J Naylor, C Raymond, M Rosetti, R Santos, A Sheridan, C Sougnez, Y Stange-Thomann, N Stojanovic, A Subramanian, D Wyman, J Rogers, J Sulston, R Ainscough, S Beck, D Bentley, J Burton, C Clee, N Carter, A Coulson, R Deadman, P Deloukas, A Dunham, I Dunham, R Durbin, L French, D Grafham, S Gregory, T Hubbard, S Humphray, A Hunt, M Jones, C Lloyd, A McMurray, L Matthews, S Mercer, S Milne, JC Mullikin, A Mungall, R Plumb, M Ross, R Shownkeen, S Sims, RH Waterston, RK Wilson, LW Hillier, JD McPherson, MA Marra, ER Mardis, LA Fulton, AT Chinwalla, KH Pepin, WR Gish, SL Chissoe, MC Wendl, KD Delehaunty, TL Miner, A Delehaunty, JB Kramer, LL Cook, RS Fulton, DL Johnson, PJ Minx, SW Clifton, T Hawkins, E Branscomb, P Predki, P Richardson, S Wenning, T Slezak, N Doggett, JF Cheng, A Olsen, S Lucas, C Elkin, E Uberbacher, M Frazier, RA Gibbs, DM Muzny, SE Scherer, JB Bouck, EJ Sodergren, KC Worley, CM Rives, JH Gorrell, ML Metzker, SL Naylor, RS Kucherlapati, DL Nelson, GM Weinstock, Y Sakaki, A Fujiyama, M Hattori, T Yada, A Toyoda, T Itoh, C Kawagoe, H Watanabe, Y Totoki, T Taylor, J Weissenbach, R Heilig, W Saurin, F Artiguenave, P Brottier, T Bruls, E Pelletier, C Robert, P Wincker, DR Smith, L Doucette-Stamm, M Rubenfield, K Weinstock, HM Lee, J Dubois, A Rosenthal, M Platzer, G Nyakatura, S Taudien, A Rump, H Yang, J Yu, J Wang, G Huang, J Gu, L Hood, L Rowen, A Madan, S Qin, RW Davis, NA Federspiel, AP Abola, MJ Proctor, RM Myers, J Schmutz, M Dickson, J Grimwood, DR Cox, MV Olson, R Kaul, C Raymond, N Shimizu, K Kawasaki, S Minoshima, GA Evans, M Athanasiou, R Schultz, BA Roe, F Chen, H Pan, J Ramser, H Lehrach, R Reinhardt, WR McCombie, la Bastide M de, N Dedhia, H Blöcker, K Hornischer, G Nordsiek, R Agarwala, L Aravind, JA Bailey, A Bateman, S Batzoglou, E Birney, P Bork, DG Brown, CB Burge, L Cerutti, HC Chen, D Church, M Clamp, RR Copley, T Doerks, SR Eddy, EE Eichler, TS Furey, J Galagan, JG Gilbert, C Harmon, Y Hayashizaki, D Haussler, H Hermjakob, K Hokamp, W Jang, LS Johnson, TA Jones, S Kasif, A Kaspryzk, S Kennedy, WJ Kent, P Kitts, EV Koonin, I Korf, D Kulp, D Lancet, TM Lowe, A McLysaght, T Mikkelsen, JV Moran, N Mulder, VJ Pollara, CP Ponting, G Schuler, J Schultz, G Slater, AF Smit, E Stupka, J Szustakowki, D Thierry-Mieg, J Thierry-Mieg, L Wagner, J Wallis, R Wheeler, A Williams, YI Wolf, KH Wolfe, SP Yang, RF Yeh, F Collins, MS Guyer, J Peterson, A Felsenfeld, KA Wetterstrand, A Patrinos, MJ Morgan, Jong P de, JJ Catanese, K Osoegawa, H Shizuya, S Choi, YJ Chen, J; International Human Genome Sequencing Consortium Szustakowki. Initial sequencing and analysis of the human genome. Nature 2001; 409(6822): 860–921 https://doi.org/10.1038/35057062 pmid: 11237011
46	JC Venter, MD Adams, EW Myers, PW Li, RJ Mural, GG Sutton, HO Smith, M Yandell, CA Evans, RA Holt, JD Gocayne, P Amanatides, RM Ballew, DH Huson, JR Wortman, Q Zhang, CD Kodira, XH Zheng, L Chen, M Skupski, G Subramanian, PD Thomas, J Zhang, Miklos GL Gabor, C Nelson, S Broder, AG Clark, J Nadeau, VA McKusick, N Zinder, AJ Levine, RJ Roberts, M Simon, C Slayman, M Hunkapiller, R Bolanos, A Delcher, I Dew, D Fasulo, M Flanigan, L Florea, A Halpern, S Hannenhalli, S Kravitz, S Levy, C Mobarry, K Reinert, K Remington, J Abu-Threideh, E Beasley, K Biddick, V Bonazzi, R Brandon, M Cargill, I Chandramouliswaran, R Charlab, K Chaturvedi, Z Deng, Francesco V Di, P Dunn, K Eilbeck, C Evangelista, AE Gabrielian, W Gan, W Ge, F Gong, Z Gu, P Guan, TJ Heiman, ME Higgins, RR Ji, Z Ke, KA Ketchum, Z Lai, Y Lei, Z Li, J Li, Y Liang, X Lin, F Lu, GV Merkulov, N Milshina, HM Moore, AK Naik, VA Narayan, B Neelam, D Nusskern, DB Rusch, S Salzberg, W Shao, B Shue, J Sun, Z Wang, A Wang, X Wang, J Wang, M Wei, R Wides, C Xiao, C Yan, A Yao, J Ye, M Zhan, W Zhang, H Zhang, Q Zhao, L Zheng, F Zhong, W Zhong, S Zhu, S Zhao, D Gilbert, S Baumhueter, G Spier, C Carter, A Cravchik, T Woodage, F Ali, H An, A Awe, D Baldwin, H Baden, M Barnstead, I Barrow, K Beeson, D Busam, A Carver, A Center, ML Cheng, L Curry, S Danaher, L Davenport, R Desilets, S Dietz, K Dodson, L Doup, S Ferriera, N Garg, A Gluecksmann, B Hart, J Haynes, C Haynes, C Heiner, S Hladun, D Hostin, J Houck, T Howland, C Ibegwam, J Johnson, F Kalush, L Kline, S Koduru, A Love, F Mann, D May, S McCawley, T McIntosh, I McMullen, M Moy, L Moy, B Murphy, K Nelson, C Pfannkoch, E Pratts, V Puri, H Qureshi, M Reardon, R Rodriguez, YH Rogers, D Romblad, B Ruhfel, R Scott, C Sitter, M Smallwood, E Stewart, R Strong, E Suh, R Thomas, NN Tint, S Tse, C Vech, G Wang, J Wetter, S Williams, M Williams, S Windsor, E Winn-Deen, K Wolfe, J Zaveri, K Zaveri, JF Abril, R Guigó, MJ Campbell, KV Sjolander, B Karlak, A Kejariwal, H Mi, B Lazareva, T Hatton, A Narechania, K Diemer, A Muruganujan, N Guo, S Sato, V Bafna, S Istrail, R Lippert, R Schwartz, B Walenz, S Yooseph, D Allen, A Basu, J Baxendale, L Blick, M Caminha, J Carnes-Stine, P Caulk, YH Chiang, M Coyne, C Dahlke, Mays A Deslattes, M Dombroski, M Donnelly, D Ely, S Esparham, C Fosler, H Gire, S Glanowski, K Glasser, A Glodek, M Gorokhov, K Graham, B Gropman, M Harris, J Heil, S Henderson, J Hoover, D Jennings, C Jordan, J Jordan, J Kasha, L Kagan, C Kraft, A Levitsky, M Lewis, X Liu, J Lopez, D Ma, W Majoros, J McDaniel, S Murphy, M Newman, T Nguyen, N Nguyen, M Nodell, S Pan, J Peck, M Peterson, W Rowe, R Sanders, J Scott, M Simpson, T Smith, A Sprague, T Stockwell, R Turner, E Venter, M Wang, M Wen, D Wu, M Wu, A Xia, A Zandieh, X Zhu. The sequence of the human genome. Science 2001; 291(5507): 1304–1351 https://doi.org/10.1126/science.1058040 pmid: 11181995
47	RA Raff. Evo-devo: the evolution of a new discipline. Nat Rev Genet 2000; 1(1): 74–79 https://doi.org/10.1038/35049594 pmid: 11262880
48	AM Sinclair, EA Dzierzak. Cloning of the complete Ly-6E.1 gene and identification of DNase I hypersensitive sites corresponding to expression in hematopoietic cells. Blood 1993; 82(10): 3052–3062 https://doi.org/10.1182/blood.V82.10.3052.3052 pmid: 8219196
49	A McLysaght, D Guerzoni. New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation. Philos Trans R Soc Lond B Biol Sci 2015; 370(1678): 20140332 https://doi.org/10.1098/rstb.2014.0332
50	JP Adelman, CT Bond, J Douglass, E Herbert. Two mammalian genes transcribed from opposite strands of the same DNA locus. Science 1987; 235(4795): 1514–1517 https://doi.org/10.1126/science.3547652 pmid: 3547652
51	S Katayama, Y Tomaru, T Kasukawa, K Waki, M Nakanishi, M Nakamura, H Nishida, CC Yap, M Suzuki, J Kawai, H Suzuki, P Carninci, Y Hayashizaki, C Wells, M Frith, T Ravasi, KC Pang, J Hallinan, J Mattick, DA Hume, L Lipovich, S Batalov, PG Engström, Y Mizuno, MA Faghihi, A Sandelin, AM Chalk, S Mottagui-Tabar, Z Liang, B Lenhard, C; RIKEN Genome Exploration Research Group; Genome Science Group (Genome Network Project Core Group); FANTOM Consortium Wahlestedt. Antisense transcription in the mammalian transcriptome. Science 2005; 309(5740): 1564–1566 https://doi.org/10.1126/science.1112009 pmid: 16141073
52	EJ Strobel, AM Yu, JB Lucks. High-throughput determination of RNA structures. Nat Rev Genet 2018; 19(10): 615–634 https://doi.org/10.1038/s41576-018-0034-x pmid: 30054568
53	JF Hu, D Yim, D Ma, SM Huber, N Davis, JM Bacusmo, S Vermeulen, J Zhou, TJ Begley, MS DeMott, SS Levine, Crécy-Lagard V de, PC Dedon, B Cao. Quantitative mapping of the cellular small RNA landscape with AQRNA-seq. Nat Biotechnol 2021; 39(8): 978–988 https://doi.org/10.1038/s41587-021-00874-y pmid: 33859402
54	Y Kong, H Hu, Y Shan, Z Zhou, K Zen, Y Sun, R Yang, Z Fu, X Chen. Accurate quantification of 3′-terminal 2′-O-methylated small RNAs by utilizing oxidative deep sequencing and stem-loop RT-qPCR. Front Med 2022; 16(2): 240–250 https://doi.org/10.1007/s11684-021-0909-7 pmid: 35416629
55	G Upadhyay. Emerging role of lymphocyte antigen-6 family of genes in cancer and immune cells. Front Immunol 2019; 10: 819 https://doi.org/10.3389/fimmu.2019.00819 pmid: 31068932

[1]	Fangyi Dong, Li Chen, Chaoxian Zhao, Xiaoyang Li, Yun Tan, Huan Song, Wen Jin, Hongming Zhu, Yunxiang Zhang, Kai Xue, Junmin Li, Kankan Wang. Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia[J]. Front. Med., 2022, 16(6): 909-918.
[2]	Shoubin Zhan, Ping Yang, Shengkai Zhou, Ye Xu, Rui Xu, Gaoli Liang, Chenyu Zhang, Xi Chen, Liuqing Yang, Fangfang Jin, Yanbo Wang. Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis[J]. Front. Med., 2022, 16(2): 216-226.
[3]	Ziqi Chen, Xiaoqi Huang, Qiyong Gong, Bharat B. Biswal. Translational application of neuroimaging in major depressive disorder: a review of psychoradiological studies[J]. Front. Med., 2021, 15(4): 528-540.
[4]	Solmaz Ohadian Moghadam, Seyed Ali Momeni. Human microbiome and prostate cancer development: current insights into the prevention and treatment[J]. Front. Med., 2021, 15(1): 11-32.
[5]	Weiqi Rong, Yang Zhang, Lei Yang, Lin Feng, Baojun Wei, Fan Wu, Liming Wang, Yanning Gao, Shujun Cheng, Jianxiong Wu, Ting Xiao. Post-surgical resection prognostic value of combined OPN, MMP7, and PSG9 plasma biomarkers in hepatocellular carcinoma[J]. Front. Med., 2019, 13(2): 250-258.
[6]	Chenyang Wang, Qiurong Li, Jieshou Li. Gut microbiota and its implications in small bowel transplantation[J]. Front. Med., 2018, 12(3): 239-248.
[7]	Shuye Zhang, Fusheng Wang, Zheng Zhang. Current advances in the elimination of hepatitis B in China by 2030[J]. Front. Med., 2017, 11(4): 490-501.
[8]	Changlin Cao, Jingxian Gu, Jingyao Zhang. Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis of infectious diseases[J]. Front. Med., 2017, 11(2): 169-177.
[9]	Lei Huang,Aman Xu. Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination[J]. Front. Med., 2017, 11(1): 20-31.
[10]	Yi Cao. Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications[J]. Front. Med., 2015, 9(3): 261-274.
[11]	Feng Wang,Chen Chen,Daowen Wang. Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets[J]. Front. Med., 2014, 8(4): 404-418.
[12]	Lunxiu Qin. Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies[J]. Front Med, 2014, 8(1): 24-32.
[13]	Xiao Liu, Hui Ren, Daizhi Peng. Sepsis biomarkers: an omics perspective[J]. Front Med, 2014, 8(1): 58-67.
[14]	Chuanbao Zhang, Zhaoshi Bao, Wei Zhang, Tao Jiang. Progress on molecular biomarkers and classification of malignant gliomas[J]. Front Med, 2013, 7(2): 150-156.
[15]	Chen WANG PhD, MD, Zhen-Guo ZHAI PhD, MD, Ying H. SHEN PhD, MD, Lan ZHAO PhD, MD, . Clinical and genetic risk factors for venous thromboembolism in Chinese population[J]. Front. Med., 2010, 4(1): 29-35.

Viewed

Full text

Abstract

Cited

Shared

Discussed