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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

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Frontiers of Medicine  2019, Vol. 13 Issue (2): 250-258   https://doi.org/10.1007/s11684-018-0632-1
  本期目录
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
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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.
Key words： biomarkers    OPN    MMP7    PSG9    HCC    prognosis
收稿日期: 2017-07-06      出版日期: 2019-03-28
Corresponding Author(s): Jianxiong Wu,Ting Xiao   
 引用本文:   
. [J]. Frontiers of Medicine, 2019, 13(2): 250-258.
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. Front. Med., 2019, 13(2): 250-258.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-018-0632-1
https://academic.hep.com.cn/fmd/CN/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  
Fig.1  
Fig.2  
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  
Fig.3  
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