Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (2) : 250-258    https://doi.org/10.1007/s11684-018-0632-1
RESEARCH ARTICLE
Post-surgical resection prognostic value of combined OPN, MMP7, and PSG9 plasma biomarkers in hepatocellular carcinoma
Weiqi Rong1, Yang Zhang1, Lei Yang2, Lin Feng2, Baojun Wei3, Fan Wu1, Liming Wang1, Yanning Gao2, Shujun Cheng2, Jianxiong Wu1(), Ting Xiao2()
1. Department of Abdominal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
2. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
3. Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
 Download: PDF(443 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Biomarkers for hepatocellular carcinoma (HCC) following curative resection are not currently sufficient for prognostic indication of overall survival (OS) and disease-free survival (DFS). The aim of this study was to investigate the prognostic performance of osteopontin (OPN), matrix metalloproteinase 7 (MMP7), and pregnancy specific glycoprotein 9 (PSG9) in patients with HCC. A total of 179 prospective patients with HCC provided plasma before hepatectomy. Plasma OPN, MMP7, and PSG9 levels were determined by enzyme-linked immunosorbent assay. Correlations between plasma levels, clinical parameters, and outcomes (OS and DFS) were overall analyzed. High OPN (≥149.97 ng/mL), MMP7 (≥2.28 ng/mL), and PSG9 (≥45.59 ng/mL) were prognostic indicators of reduced OS (P<0.001, P<0.001, and P=0.007, respectively). Plasma PSG9 protein level was an independent factor in predicting OS (P=0.008) and DFS (P=0.038). Plasma OPN+MMP7+PSG9 elevation in combination was a prognostic factor for OS (P<0.001). OPN was demonstrated to be a risk factor-associated OS in stage I patients with HCC and patients with low α-fetoprotein levels (<20 ng/mL). These findings suggested that OPN, MMP7, PSG9 and their combined panels may be useful for aiding in tumor recurrence and mortality risk prediction of patients with HCC, particularly in the early stage of HCC carcinogenesis.

Keywords biomarkers      OPN      MMP7      PSG9      HCC      prognosis     
Corresponding Author(s): Jianxiong Wu,Ting Xiao   
Just Accepted Date: 11 April 2018   Online First Date: 16 May 2018    Issue Date: 28 March 2019
 Cite this article:   
Weiqi Rong,Yang Zhang,Lei Yang, et al. Post-surgical resection prognostic value of combined OPN, MMP7, and PSG9 plasma biomarkers in hepatocellular carcinoma[J]. Front. Med., 2019, 13(2): 250-258.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0632-1
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I2/250
Clinical parameters Plasma levels (mean±SD)
OPN MMP7 PSG9
Age (year) ≤55 (n = 91) 138.85±69.86 2.32±4.13 33.96±122.48
>55 (n = 88) 202.95±190.05 4.28±14.20 27.30±50.33
P value 0.007 0.046 0.969
Sex Female (n = 39) 207.08±246.41 1.95±1.98 47.10±182.58
Male (n = 140) 160.14±100.03 3.66±11.70 26.11±45.87
P value 0.620 0.576 0.600
AFP (ng/mL) <20 (n = 116) 167.55±127.00 2.38±3.51 27.47±50.96
≥20 (n = 63) 175.55±175.41 4.96±16.84 36.61±143.14
P value 0.428 0.447 0.894
Hepatitis history Yes (n = 165) 166.78±144.46 3.17±10.62 32.09±97.75
No (n = 14) 212.60±155.86 4.62±7.55 14.11±8.93
P value 0.302 0.597 0.480
Liver cirrhosis Yes (n = 131) 162.48±114.50 3.84±12.05 26.54±46.97
No (n = 48) 191.87±207.86 1.77±2.31 42.01±164.85
P value 0.584 0.073 0.936
Tumor differentiation Well/moderate (n = 140) 161.14±135.00 3.47±11.62 34.03±105.46
Poor (n = 39) 203.48±176.01 2.64±3.48 18.67±22.63
P value 0.086 0.146 0.962
Tumor size (cm) ≤3 (n = 123) 120.18±57.59 2.69±4.05 24.82±52.583
>3 (n = 56) 193.21±166.39 4.59±17.65 3.36±107.80
P value <0.001 0.241 0.251
TNM stage I (n = 86) 137.15±69.55 2.10±3.27 34.38±127.76
II+ III+ IV (n = 93) 201.08±185.67 4.38±14.03 27.27±44.57
P value 0.006 0.285 0.382
Tumor number Single (n = 156) 162.07±108.21 2.84±9.92 30.51±99.09
Multiple (n = 23) 226.66±291.30 6.32±13.07 31.89±47.88
P value 0.889 0.002 0.315
Vascular invasion Yes (n = 66) 180.51±133.81 3.62±14.70 27.40±46.45
No (n = 113) 164.43±152.09 3.09±6.82 32.60±113.04
P value 0.094 0.095 0.747
Capsule invasion Yes (n = 61) 150.55±100.41 2.06±2.52 29.48±59.54
No (n = 118) 180.61±163.40 3.92±12.66 31.31±107.80
P value 0.148 0.314 0.364
OS-Event Yes (n = 29) 200.80±107.73 2.41±2.70 63.23±209.37
?(death) No (n = 150) 164.48±151.24 3.45±11.30 24.39±45.50
P value 0.003 0.302 0.420
DFS-Event Yes (n = 77) 190.23±144.22 2.70±3.99 38.02±133.17
?(recurrence) No (n = 102) 155.37±145.27 3.73±13.35 25.15±46.39
P value 0.006 0.335 0.447
Tab.1  Association of clinical parameters and plasma levels of OPN, MMP7, and PSG9 in HCCa
Fig.1  Estimation of discriminatory performance of OPN, MMP7, PSG9, and AFP optimal cutoff values indicated by time-dependent receiver operating curve (ROC) corresponding to overall survival time. (A) Dynamic AUC plots for OPN, MMP7, PSG9, and AFP. Time-dependent ROC curves for determining optimal cutoff values of OPN (B), MMP7 (C), PSG9 (D), and AFP (E). AUC, area under the ROC curve.
Fig.2  Kaplan–Meier analysis indicated low overall survival (OS) rates with high plasma OPN, MMP7, and PSG9 levels in patients with hepatocellular carcinoma (HCC). Cumulative OS curves for OPN (A), MMP7 (B), and PSG9 (C). (D) Kaplan–Meier analysis of OS for combined plasma levels of OPN, MMP7, or PSG9. Low, all three protein plasma levels were below cutoff (OPN<149.97 ng/mL, MMP7<2.28 ng/mL, PSG9<45.59 ng/mL, n=86). High, at least one of the three protein plasma levels was above cutoff (n=93).
Variables OS DFS
Univariate Multivariate Univariate Multivariate
P HR
(95% CI)
P P HR
(95% CI)
P
Age, year
?(≤55/>55)
0.330 NA 0.228 NA
Sex
?(female/male)
0.499 NA 0.323 NA
HBeAg
?(negative/positive)
0.628 NA 0.800 NA
Liver cirrhosis
?(yes/no)
0.655 NA 0.081 NA
Differentiation
?(well-moderate/ poor)
0.035 1.176
(0.787−3.739)
0.174 0.007 1.808
(1.103−2.964)
0.019
Tumor size
?(≤3/>3, cm)
0.025 0.519
(0.169−1.597)
0.253 0.012 0.683
(0.390−1.199)
0.184
TNM stage
?(I/II+ III+ IV)
0.130 NA 0.295 NA
Tumor number
?(single/multiple)
0.117 NA 0.064 NA
Vascular invasion
?(yes/no)
0.759 NA 0.971 NA
Capsule invasion
?(yes/no)
0.112 NA 0.077 NA
OPN, ng/mL
?(low/high)
<0.001 2.331
(0.991−5.486)
0.053 <0.001 1.658
(0.995−2.763)
0.052
MMP7, ng/mL
?(low/high)
0.009 1.975
(0.893−4.370)
0.093 0.013 1.469
(0.884−2.441)
0.138
PSG9, ng/mL
?(low/high)
0.011 3.563
(1.384−9.172)
0.008 0.059 2.140
(1.042−4.398)
0.038
Combineda <0.001 NA <0.001 NA
Tab.2  Univariate and multivariate analyses of factors associated with survival and recurrence
Fig.3  Prognostic value of OPN in early-stage patients with HCC (stage I) and patients with low AFP levels (<20 ng/mL). (A) Stage I HCC with high plasma OPN levels had significantly shorter OS compared with patients with low OPN levels. (B) OPN was demonstrated to be a risk factor associated with OS in patients with AFP<20 ng/mL.
1 LATorre, F Bray, RLSiegel, JFerlay, JLortet-Tieulent, AJemal. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87–108
https://doi.org/10.3322/caac.21262 pmid: 25651787
2 TLu, WK Seto, RXZhu, CLLai, MF Yuen. Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection. World J Gastroenterol 2013; 19(47): 8887–8894
https://doi.org/10.3748/wjg.v19.i47.8887 pmid: 24379612
3 TKumada, H Toyoda, TTada, SKiriyama, MTanikawa, YHisanaga, AKanamori, JTanaka, CKagebayashi, SSatomura. High-sensitivity Lens culinaris agglutinin-reactive α-fetoprotein assay predicts early detection of hepatocellular carcinoma. J Gastroenterol 2014; 49(3): 555–563
https://doi.org/10.1007/s00535-013-0883-1 pmid: 24057163
4 AKornberg, U Witt, EMatevossian, BKüpper, VAssfalg, ADrzezga, NHüser, MWildgruber, HFriess. Extended postinterventional tumor necrosis-implication for outcome in liver transplant patients with advanced HCC. PLoS One 2013; 8(1): e53960
https://doi.org/10.1371/journal.pone.0053960 pmid: 23349774
5 JCheng, W Wang, CSun, MLi, B Wang, YLv. Meta-analysis of the prognostic and diagnostic significance of serum/plasma osteopontin in hepatocellular carcinoma. J Clin Gastroenterol 2014; 48(9): 806–814
https://doi.org/10.1097/MCG.0000000000000018 pmid: 24247813
6 RTateishi, S Shiina, HYoshida, TTeratani, SObi, N Yamashiki, HYoshida, MAkamatsu, TKawabe, MOmata. Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers. Hepatology 2006; 44(6): 1518–1527
https://doi.org/10.1002/hep.21408 pmid: 17133456
7 CLugassy, M Wadehra, XLi, MCorselli, DAkhavan, SWBinder, BPéault, AJCochran, PSMischel, HKKleinman, RLBarnhill. Pilot study on “pericytic mimicry” and potential embryonic/stem cell properties of angiotropic melanoma cells interacting with the abluminal vascular surface. Cancer Microenviron 2013; 6(1): 19–29
https://doi.org/10.1007/s12307-012-0128-5 pmid: 23275074
8 SBlank, Q Wang, MIFiel, WLuan, KW Kim, HKadri, JMandeli, SPHiotis. Assessing prognostic significance of preoperative α-fetoprotein in hepatitis B-associated hepatocellular carcinoma: normal is not the new normal. Ann Surg Oncol 2014; 21(3): 986–994
https://doi.org/10.1245/s10434-013-3357-z pmid: 24232510
9 KShimada, Y Sakamoto, MEsaki, TKosuge, CMorizane, MIkeda, HUeno, T Okusaka, YArai, KTakayasu. Analysis of prognostic factors affecting survival after initial recurrence and treatment efficacy for recurrence in patients undergoing potentially curative hepatectomy for hepatocellular carcinoma. Ann Surg Oncol 2007; 14(8): 2337–2347
https://doi.org/10.1245/s10434-007-9415-7 pmid: 17503155
10 JAMarrero, Z Feng, YWang, MHNguyen, ASBefeler, LRRoberts, KRReddy, DHarnois, JMLlovet, DNormolle, JDalhgren, DChia, AS Lok, PDWagner, SSrivastava, MSchwartz. α-fetoprotein, des-γ carboxyprothrombin, and lectin-bound α-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009; 137(1): 110–118
https://doi.org/10.1053/j.gastro.2009.04.005 pmid: 19362088
11 SJFu, CY Qi, WKXiao, SQLi, BG Peng, LJLiang. Glypican-3 is a potential prognostic biomarker for hepatocellular carcinoma after curative resection. Surgery 2013; 154(3): 536–544
https://doi.org/10.1016/j.surg.2013.02.014 pmid: 23601901
12 YMao, H Yang, HXu, XLu, X Sang, SDu, HZhao, W Chen, YXu, TChi, Z Yang, JCai, HLi, J Chen, SZhong, SRMohanti, RLopez-Soler, JMMillis, JHuang, HZhang. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut 2010; 59(12): 1687–1693
https://doi.org/10.1136/gut.2010.214916 pmid: 20876776
13 MKobayashi, T Hosaka, KIkeda, YSeko, Y Kawamura, HSezaki, NAkuta, FSuzuki, YSuzuki, SSaitoh, YArase, HKumada. Highly sensitive AFP-L3% assay is useful for predicting recurrence of hepatocellular carcinoma after curative treatment pre- and postoperatively. Hepatol Res 2011; 41(11): 1036–1045
https://doi.org/10.1111/j.1872-034X.2011.00858.x pmid: 21883741
14 JLiu, K Xu, MChase, YJi, JK Logan, RJBuchsbaum. Tiam1-regulated osteopontin in senescent fibroblasts contributes to the migration and invasion of associated epithelial cells. J Cell Sci 2012; 125(Pt 2): 376–386
https://doi.org/10.1242/jcs.089466 pmid: 22302986
15 WKSyn, KM Agboola, MSwiderska, GAMichelotti, ELiaskou, HPang, G Xie, GPhilips, ISChan, GFKaraca, TAPereira, YChen, Z Mi, PCKuo, SSChoi, CDGuy, MF Abdelmalek, AMDiehl. NKT-associated hedgehog and osteopontin drive fibrogenesis in non-alcoholic fatty liver disease. Gut 2012; 61(9): 1323–1329
https://doi.org/10.1136/gutjnl-2011-301857 pmid: 22427237
16 JSun, HM Xu, HJZhou, QZDong, YZhao, LY Fu, ZYHei, QHYe, N Ren, HLJia, LXQin. The prognostic significance of preoperative plasma levels of osteopontin in patients with TNM stage-I of hepatocellular carcinoma. J Cancer Res Clin Oncol 2010; 136(1): 1–7
https://doi.org/10.1007/s00432-009-0629-x pmid: 19593583
17 SShang, A Plymoth, SGe, ZFeng, HR Rosen, SSangrajrang, PHainaut, JAMarrero, LBeretta. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 2012; 55(2): 483–490
https://doi.org/10.1002/hep.24703 pmid: 21953299
18 SPhilip, GC Kundu. Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through IκBα/IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. J Biol Chem 2003; 278(16): 14487–14497
https://doi.org/10.1074/jbc.M207309200 pmid: 12473670
19 TXiao, W Ying, LLi, ZHu, Y Ma, LJiao, JMa, Y Cai, DLin, SGuo, N Han, XDi, MLi, D Zhang, KSu, JYuan, H Zheng, MGao, JHe, S Shi, WLi, NXu, H Zhang, YLiu, KZhang, YGao, X Qian, SCheng. An approach to studying lung cancer-related proteins in human blood. Mol Cell Proteomics 2005; 4(10): 1480–1486
https://doi.org/10.1074/mcp.M500055-MCP200 pmid: 15970581
20 LYang, W Rong, TXiao, YZhang, BXu, Y Liu, LWang, FWu, J Qi, XZhao, HWang, N Han, SGuo, JWu, Y Gao, SCheng. Secretory/releasing proteome-based identification of plasma biomarkers in HBV-associated hepatocellular carcinoma. Sci China Life Sci 2013; 56(7): 638–646
https://doi.org/10.1007/s11427-013-4497-x pmid: 23749381
21 YZhang, B Xu, YLiu, HYao, N Lu, BLi, JGao, S Guo, NHan, JQi, K Zhang, SCheng, HWang, X Zhang, TXiao, LWu, Y Gao. The ovarian cancer-derived secretory/releasing proteome: a repertoire of tumor markers. Proteomics 2012; 12(11): 1883–1891
https://doi.org/10.1002/pmic.201100654 pmid: 22623176
22 JBruix, M Sherman; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53(3): 1020–1022
https://doi.org/10.1002/hep.24199 pmid: 21374666
23 SBEdge, CC Compton. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010; 17(6):1471–1474
24 QShen, J Fan, XRYang, YTan, W Zhao, YXu, NWang, Y Niu, ZWu, JZhou, SJ Qiu, YHShi, BYu, N Tang, WChu, MWang, J Wu, ZZhang, SYang, J Gu, HWang, WQin. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol 2012; 13(8): 817–826
https://doi.org/10.1016/S1470-2045(12)70233-4 pmid: 22738799
25 JLambert, S Chevret. Summary measure of discrimination in survival models based on cumulative/dynamic time-dependent ROC curves. Stat Methods Med Res 2016; 25(5): 2088–2102
pmid: 24395866
26 WZhu, L Guo, BZhang, LLou, Z Lin, XZhu, NRen, Q Dong, QYe, LQin. Combination of osteopontin with peritumoral infiltrating macrophages is associated with poor prognosis of early-stage hepatocellular carcinoma after curative resection. Ann Surg Oncol 2014; 21(4): 1304–1313
https://doi.org/10.1245/s10434-013-3445-0 pmid: 24366422
27 WSieghart, X Wang, KSchmid, MPinter, FKönig, MBodingbauer, FWrba, S Rasoul-Rockenschaub, MPeck-Radosavljevic. Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol 2011; 54(1): 89–97
https://doi.org/10.1016/j.jhep.2010.06.030 pmid: 20970216
28 HZhang, QH Ye, NRen, LZhao, YF Wang, XWu, HCSun, L Wang, BHZhang, YKLiu, ZY Tang, LXQin. The prognostic significance of preoperative plasma levels of osteopontin in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 2006; 132(11): 709–717
https://doi.org/10.1007/s00432-006-0119-3 pmid: 16786357
29 RXChen, YH Xia, JFCui, TCXue, SL Ye. Osteopontin, a single marker for predicting the prognosis of patients with tumor-node-metastasis stage I hepatocellular carcinoma after surgical resection. J Gastroenterol Hepatol 2010; 25(8): 1435–1442
https://doi.org/10.1111/j.1440-1746.2010.06277.x pmid: 20659235
30 MWang, A Mehta, TMBlock, JMarrero, AMDi Bisceglie, KDevarajan. A comparison of statistical methods for the detection of hepatocellular carcinoma based on serum biomarkers and clinical variables. BMC Med Genomics 2013; 6 (Suppl 3):S9
https://doi.org/10.1186/1755-8794-6-S3-S9 pmid: 24564861
31 YIshii, Y Nakasato, SKobayashi, YYamazaki, TAoki. A study on angiogenesis-related matrix metalloproteinase networks in primary hepatocellular carcinoma. J Exp Clin Cancer Res 2003; 22(3): 461–470
pmid: 14582707
32 KKessenbrock, V Plaks, ZWerb. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010; 141(1): 52–67
https://doi.org/10.1016/j.cell.2010.03.015 pmid: 20371345
33 BLiang, R Chen, TWang, LCao, Y Liu, FYin, MZhu, X Fan, YLiang, LZhang, YGuo, J Zhao. Myeloid differentiation factor 88 promotes growth and metastasis of human hepatocellular carcinoma. Clin Cancer Res 2013; 19(11): 2905–2916
https://doi.org/10.1158/1078-0432.CCR-12-1245 pmid: 23549880
34 TMHung, SC Chang, WHYu, YWWang, CHuang, SCLu, PH Lee, MFChang. A novel nonsynonymous variant of matrix metalloproteinase-7 confers risk of liver cirrhosis. Hepatology 2009; 50(4): 1184–1193
https://doi.org/10.1002/hep.23137 pmid: 19676133
35 SSalahshor, J Goncalves, RChetty, SGallinger, JRWoodgett. Differential gene expression profile reveals deregulation of pregnancy specific β1 glycoprotein 9 early during colorectal carcinogenesis. BMC Cancer 2005; 5:66
https://doi.org/10.1186/1471-2407-5-66 pmid: 15982419
36 FALisboa, J Warren, GSulkowski, MAparicio, GDavid, EZudaire, GSDveksler. Pregnancy-specific glycoprotein 1 induces endothelial tubulogenesis through interaction with cell surface proteoglycans. J Biol Chem 2011; 286(9): 7577–7586
https://doi.org/10.1074/jbc.M110.161810 pmid: 21193412
37 LXQin, ZY Tang. Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature. J Cancer Res Clin Oncol 2004; 130(9): 497–513
https://doi.org/10.1007/s00432-004-0572-9 pmid: 15205947
38 AOsaki, T Suda, KKamimura, ATsuchiya, YTamura, MTakamura, MIgarashi, HKawai, SYamagiwa, YAoyagi. A safe and effective dose of cisplatin in hepatic arterial infusion chemotherapy for hepatocellular carcinoma. Cancer Med 2013; 2(1): 86–98
https://doi.org/10.1002/cam4.55 pmid: 24133631
39 MSherman. Recurrence of hepatocellular carcinoma. N Engl J Med 2008; 359(19): 2045–2047
https://doi.org/10.1056/NEJMe0807581 pmid: 18923166
40 JCWu, YH Huang, GYChau, CWSu, CR Lai, PCLee, TIHuo, IJ Sheen, SDLee, WYLui. Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma. J Hepatol 2009; 51(5): 890–897
https://doi.org/10.1016/j.jhep.2009.07.009 pmid: 19747749
[1] Huanping Wang, Haitao Meng, Jinghan Wang, Yinjun Lou, Yile Zhou, Peipei Lin, Fenglin Li, Lin Liu, Huan Xu, Min Yang, Jie Jin. Clinical characteristics and prognostic values of 1p32.3 deletion detected through fluorescence in situ hybridization in patients with newly diagnosed multiple myeloma: a single-center study in China[J]. Front. Med., 2020, 14(3): 327-334.
[2] Yanfei Zhang, Xinchun Zhao, Yongchun Zhou, Min Wang, Guangbiao Zhou. Identification of an E3 ligase-encoding gene RFWD3 in non-small cell lung cancer[J]. Front. Med., 2020, 14(3): 318-326.
[3] Yue Wang, Jinxia Zhang, Yunfan Wang, Shufang Wang, Yu Zhang, Qi Miao, Fei Gao, Huiying He. Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma[J]. Front. Med., 2019, 13(6): 730-740.
[4] Wenjing Wang, Shigang Ding, Hejun Zhang, Jun Li, Jun Zhan, Hongquan Zhang. G protein-coupled receptor LGR6 is an independent risk factor for colon adenocarcinoma[J]. Front. Med., 2019, 13(4): 482-491.
[5] Yiwen Cao, Zhenhua Liu, Wen Wu, Ying Qian, Qin Shi, Rong Shen, Binshen Ouyang, Pengpeng Xu, Shu Cheng, Jin Ye, Yiming Lu, Chaofu Wang, Chengde Yang, Li Wang, Weili Zhao. Presence of multiple abnormal immunologic markers is an independent prognostic factor of diffuse large B-cell lymphoma[J]. Front. Med., 2019, 13(1): 94-103.
[6] Jing Yue, Bo Zhang, Mingyue Wang, Junning Yao, Yifan Zhou, Ding Ma, Lei Jin. Effect of antitubercular treatment on the pregnancy outcomes and prognoses of patients with genital tuberculosis[J]. Front. Med., 2019, 13(1): 121-125.
[7] Bin Yang, Yan Yu, Jing Chen, Yan Zhang, Ye Yin, Nan Yu, Ge Chen, Shifei Zhu, Haiyan Huang, Yongqun Yuan, Jihui Ai, Xinyu Wang, Kezhen Li. Possibility of women treated with fertility-sparing surgery for non-epithelial ovarian tumors to safely and successfully become pregnant---a Chinese retrospective cohort study among 148 cases[J]. Front. Med., 2018, 12(5): 509-517.
[8] Sasa Nie, Zhe Feng, Lihua Xia, Jiuxu Bai, Fenglin Xiao, Jian Liu, Li Tang, Xiangmei Chen. Risk factors of prognosis after acute kidney injury in hospitalized patients[J]. Front. Med., 2017, 11(3): 393-402.
[9] 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.
[10] Lei Huang,Aman Xu. Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination[J]. Front. Med., 2017, 11(1): 20-31.
[11] Xinsen Xu,Yanyan Zhou,Runchen Miao,Wei Chen,Kai Qu,Qing Pang,Chang Liu. Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis[J]. Front. Med., 2016, 10(2): 183-190.
[12] Zhi Xu,Chunxiang Cao,Haiyan Xia,Shujing Shi,Lingzhi Hong,Xiaowei Wei,Dongying Gu,Jianmin Bian,Zijun Liu,Wenbin Huang,Yixin Zhang,Song He,Nikki Pui-Yue Lee,Jinfei Chen. Protein phosphatase magnesium-dependent 1δ is a novel tumor marker and target in hepatocellular carcinoma[J]. Front. Med., 2016, 10(1): 52-60.
[13] Aixiu Qiao,Feng Gu,Xiaojing Guo,Xinmin Zhang,Li Fu. Breast cancer-associated fibroblasts: their roles in tumor initiation, progression and clinical applications[J]. Front. Med., 2016, 10(1): 33-40.
[14] Jing Zhang,Shan Gao,Zhongping Duan,Ke-Qin Hu. Overview on acute-on-chronic liver failure[J]. Front. Med., 2016, 10(1): 1-17.
[15] Daniel Wai-Hung Ho,Alan Ka-Lun Kai,Irene Oi-Lin Ng. TCGA whole-transcriptome sequencing data reveals significantly dysregulated genes and signaling pathways in hepatocellular carcinoma[J]. Front. Med., 2015, 9(3): 322-330.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed