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Post-surgical resection prognostic value of combined OPN, MMP7, and PSG9 plasma biomarkers in hepatocellular carcinoma

  • Weiqi Rong
  • Yang Zhang
  • Lei Yang
  • Lin Feng
  • Baojun Wei
  • Fan Wu
  • Liming Wang
  • Yanning Gao
  • Shujun Cheng
  • Jianxiong Wu
  • Ting Xiao
Research Article

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 factorassociated 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 

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Notes

Acknowledgements

This work was supported by grants from the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2016-I2M-1-001), the National Natural Science Foundation of China (No. 81172035), and the National High Technology Research and Development Program of China (No. 2012AA020206).

References

  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87–108CrossRefPubMedGoogle Scholar
  2. 2.
    Lu T, Seto WK, Zhu RX, Lai CL, Yuen MF. Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection. World J Gastroenterol 2013; 19(47): 8887–8894CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kumada T, Toyoda H, Tada T, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Tanaka J, Kagebayashi C, Satomura S. Highsensitivity Lens culinaris agglutinin-reactive a-fetoprotein assay predicts early detection of hepatocellular carcinoma. J Gastroenterol 2014; 49(3): 555–563CrossRefPubMedGoogle Scholar
  4. 4.
    Kornberg A, Witt U, Matevossian E, Küpper B, Assfalg V, Drzezga A, Hüser N, Wildgruber M, Friess H. Extended postinterventional tumor necrosis-implication for outcome in liver transplant patients with advanced HCC. PLoS One 2013; 8(1): e53960CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Cheng J, Wang W, Sun C, Li M, Wang B, Lv Y. Meta-analysis of the prognostic and diagnostic significance of serum/plasma osteopontin in hepatocellular carcinoma. J Clin Gastroenterol 2014; 48(9): 806–814CrossRefPubMedGoogle Scholar
  6. 6.
    Tateishi R, Shiina S, Yoshida H, Teratani T, Obi S, Yamashiki N, Yoshida H, Akamatsu M, Kawabe T, Omata M. Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers. Hepatology 2006; 44(6): 1518–1527CrossRefPubMedGoogle Scholar
  7. 7.
    Lugassy C, Wadehra M, Li X, Corselli M, Akhavan D, Binder SW, Péault B, Cochran AJ, Mischel PS, Kleinman HK, Barnhill RL. 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): 19–29CrossRefPubMedGoogle Scholar
  8. 8.
    Blank S, Wang Q, Fiel MI, Luan W, Kim KW, Kadri H, Mandeli J, Hiotis SP. Assessing prognostic significance of preoperative a-fetoprotein in hepatitis B-associated hepatocellular carcinoma: normal is not the new normal. Ann Surg Oncol 2014; 21(3): 986–994CrossRefPubMedGoogle Scholar
  9. 9.
    Shimada K, Sakamoto Y, Esaki M, Kosuge T, Morizane C, Ikeda M, Ueno H, Okusaka T, Arai Y, Takayasu K. 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): 2337–2347CrossRefPubMedGoogle Scholar
  10. 10.
    Marrero JA, Feng Z, Wang Y, Nguyen MH, Befeler AS, Roberts LR, Reddy KR, Harnois D, Llovet JM, Normolle D, Dalhgren J, Chia D, Lok AS, Wagner PD, Srivastava S, Schwartz M. α-fetoprotein, des-γ carboxyprothrombin, and lectin-bound a-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009; 137 (1): 110–118CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Fu SJ, Qi CY, Xiao WK, Li SQ, Peng BG, Liang LJ. Glypican-3 is a potential prognostic biomarker for hepatocellular carcinoma after curative resection. Surgery 2013; 154(3): 536–544CrossRefPubMedGoogle Scholar
  12. 12.
    Mao Y, Yang H, Xu H, Lu X, Sang X, Du S, Zhao H, Chen W, Xu Y, Chi T, Yang Z, Cai J, Li H, Chen J, Zhong S, Mohanti SR, Lopez-Soler R, Millis JM, Huang J, Zhang H. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut 2010; 59(12): 1687–1693CrossRefPubMedGoogle Scholar
  13. 13.
    Kobayashi M, Hosaka T, Ikeda K, Seko Y, Kawamura Y, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Saitoh S, Arase Y, Kumada H. Highly sensitive AFP-L3% assay is useful for predicting recurrence of hepatocellular carcinoma after curative treatment pre-and postoperatively. Hepatol Res 2011; 41(11): 1036–1045CrossRefPubMedGoogle Scholar
  14. 14.
    Liu J, Xu K, Chase M, Ji Y, Logan JK, Buchsbaum RJ. Tiam1-regulated osteopontin in senescent fibroblasts contributes to the migration and invasion of associated epithelial cells. J Cell Sci 2012; 125(Pt 2): 376–386CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Syn WK, Agboola KM, Swiderska M, Michelotti GA, Liaskou E, Pang H, Xie G, Philips G, Chan IS, Karaca GF, Pereira TA, Chen Y, Mi Z, Kuo PC, Choi SS, Guy CD, Abdelmalek MF, Diehl AM. NKT-associated hedgehog and osteopontin drive fibrogenesis in non-alcoholic fatty liver disease. Gut 2012; 61(9): 1323–1329CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Sun J, Xu HM, Zhou HJ, Dong QZ, Zhao Y, Fu LY, Hei ZY, Ye QH, Ren N, Jia HL, Qin LX. 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): 1–7CrossRefPubMedGoogle Scholar
  17. 17.
    Shang S, Plymoth A, Ge S, Feng Z, Rosen HR, Sangrajrang S, Hainaut P, Marrero JA, Beretta L. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 2012; 55(2): 483–490CrossRefPubMedGoogle Scholar
  18. 18.
    Philip S, Kundu GC. Osteopontin induces nuclear factor kappa Bmediated promatrix metalloproteinase-2 activation through IkBa/IKK signaling pathways, and curcumin (diferulolylmethane) downregulates these pathways. J Biol Chem 2003; 278(16): 14487–14497CrossRefPubMedGoogle Scholar
  19. 19.
    Xiao T, Ying W, Li L, Hu Z, Ma Y, Jiao L, Ma J, Cai Y, Lin D, Guo S, Han N, Di X, Li M, Zhang D, Su K, Yuan J, Zheng H, Gao M, He J, Shi S, Li W, Xu N, Zhang H, Liu Y, Zhang K, Gao Y, Qian X, Cheng S. An approach to studying lung cancer-related proteins in human blood. Mol Cell Proteomics 2005; 4(10): 1480–1486CrossRefPubMedGoogle Scholar
  20. 20.
    Yang L, Rong W, Xiao T, Zhang Y, Xu B, Liu Y,Wang L,Wu F, Qi J, Zhao X, Wang H, Han N, Guo S, Wu J, Gao Y, Cheng S. Secretory/releasing proteome-based identification of plasma biomarkers in HBV-associated hepatocellular carcinoma. Sci China Life Sci 2013; 56(7): 638–646CrossRefPubMedGoogle Scholar
  21. 21.
    Zhang Y, Xu B, Liu Y, Yao H, Lu N, Li B, Gao J, Guo S, Han N, Qi J, Zhang K, Cheng S,Wang H, Zhang X, Xiao T,Wu L, Gao Y. The ovarian cancer-derived secretory/releasing proteome: a repertoire of tumor markers. Proteomics 2012; 12(11): 1883–1891CrossRefPubMedGoogle Scholar
  22. 22.
    Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53(3): 1020–1022CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Edge SB, Compton CC. 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):1471–1474CrossRefPubMedGoogle Scholar
  24. 24.
    Shen Q, Fan J, Yang XR, Tan Y, Zhao W, Xu Y, Wang N, Niu Y, Wu Z, Zhou J, Qiu SJ, Shi YH, Yu B, Tang N, Chu W,Wang M,Wu J, Zhang Z, Yang S, Gu J, Wang H, Qin W. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol 2012; 13(8): 817–826CrossRefPubMedGoogle Scholar
  25. 25.
    Lambert J, Chevret S. Summary measure of discrimination in survival models based on cumulative/dynamic time-dependent ROC curves. Stat Methods Med Res 2016; 25(5): 2088–2102CrossRefPubMedGoogle Scholar
  26. 26.
    Zhu W, Guo L, Zhang B, Lou L, Lin Z, Zhu X, Ren N, Dong Q, Ye Q, Qin L. 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): 1304–1313CrossRefPubMedGoogle Scholar
  27. 27.
    Sieghart W, Wang X, Schmid K, Pinter M, König F, Bodingbauer M, Wrba F, Rasoul-Rockenschaub S, Peck-Radosavljevic M. Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol 2011; 54(1): 89–97CrossRefPubMedGoogle Scholar
  28. 28.
    Zhang H, Ye QH, Ren N, Zhao L, Wang YF, Wu X, Sun HC, Wang L, Zhang BH, Liu YK, Tang ZY, Qin LX. The prognostic significance of preoperative plasma levels of osteopontin in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 2006; 132 (11): 709–717CrossRefPubMedGoogle Scholar
  29. 29.
    Chen RX, Xia YH, Cui JF, Xue TC, Ye SL. Osteopontin, a single marker for predicting the prognosis of patients with tumor-nodemetastasis stage I hepatocellular carcinoma after surgical resection. J Gastroenterol Hepatol 2010; 25(8): 1435–1442CrossRefPubMedGoogle Scholar
  30. 30.
    Wang M, Mehta A, Block TM, Marrero J, Di Bisceglie AM, Devarajan K. 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):S9CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Ishii Y, Nakasato Y, Kobayashi S, Yamazaki Y, Aoki T. A study on angiogenesis-related matrix metalloproteinase networks in primary hepatocellular carcinoma. J Exp Clin Cancer Res 2003; 22(3): 461–470PubMedGoogle Scholar
  32. 32.
    Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010; 141(1): 52–67CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Liang B, Chen R, Wang T, Cao L, Liu Y, Yin F, Zhu M, Fan X, Liang Y, Zhang L, Guo Y, Zhao J. Myeloid differentiation factor 88 promotes growth and metastasis of human hepatocellular carcinoma. Clin Cancer Res 2013; 19(11): 2905–2916CrossRefPubMedGoogle Scholar
  34. 34.
    Hung TM, Chang SC, Yu WH, Wang YW, Huang C, Lu SC, Lee PH, Chang MF. A novel nonsynonymous variant of matrix metalloproteinase-7 confers risk of liver cirrhosis. Hepatology 2009; 50(4): 1184–1193CrossRefPubMedGoogle Scholar
  35. 35.
    Salahshor S, Goncalves J, Chetty R, Gallinger S, Woodgett JR. Differential gene expreßsion profile reveals deregulation of pregnancy specific β1 glycoprotein 9 early during colorectal carcinogenesis. BMC Cancer 2005; 5:66CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Lisboa FA, Warren J, Sulkowski G, Aparicio M, David G, Zudaire E, Dveksler GS. Pregnancy-specific glycoprotein 1 induces endothelial tubulogenesis through interaction with cell surface proteoglycans. J Biol Chem 2011; 286(9): 7577–7586CrossRefPubMedGoogle Scholar
  37. 37.
    Qin LX, Tang ZY. 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): 497–513CrossRefPubMedGoogle Scholar
  38. 38.
    Osaki A, Suda T, Kamimura K, Tsuchiya A, Tamura Y, Takamura M, Igarashi M, Kawai H, Yamagiwa S, Aoyagi Y. A safe and effective dose of cisplatin in hepatic arterial infusion chemotherapy for hepatocellular carcinoma. Cancer Med 2013; 2(1): 86–98CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Sherman M. Recurrence of hepatocellular carcinoma. N Engl J Med 2008; 359(19): 2045–2047CrossRefPubMedGoogle Scholar
  40. 40.
    Wu JC, Huang YH, Chau GY, Su CW, Lai CR, Lee PC, Huo TI, Sheen IJ, Lee SD, Lui WY. Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma. J Hepatol 2009; 51 (5): 890–897CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Weiqi Rong
    • 1
  • Yang Zhang
    • 1
  • Lei Yang
    • 2
  • Lin Feng
    • 2
  • Baojun Wei
    • 3
  • Fan Wu
    • 1
  • Liming Wang
    • 1
  • Yanning Gao
    • 2
  • Shujun Cheng
    • 2
  • Jianxiong Wu
    • 1
  • Ting Xiao
    • 2
  1. 1.Department of Abdominal Surgery, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  3. 3.Clinical Laboratory, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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