Abstract
Purpose
To investigate the expression of claudin 10 in hepatocellular carcinoma (HCC) and the impact on angiogenesis and the postoperative survival of HCC patients.
Methods
The expression of claudin 10 protein was analyzed on samples from 99 HCC patients undergoing hepatectomy with immunohistochemistry and 31 fresh specimens with Western blotting. We examined the relationship between claudin 10 expression with clinicopathological factors, microvessel density (MVD), and postoperative survival.
Results
Western blotting and immunohistochemical staining showed that claudin 10 protein was highly expressed in HCC, compared with paraneoplastic liver tissue and normal liver tissue (P < 0.01). Claudin 10 protein expression levels were significantly higher in HCC specimens with microscopic venous invasion (P < 0.01). MVD in HCC increased with enhanced claudin 10 expression (P < 0.01). Kaplan–Meier survival analysis revealed that HCC patients with high claudin 10 expression had significantly shorter overall survival (P = 0.01). Multivariate analysis showed that claudin 10 expression was an independent prognostic indicator for postoperative overall survival of HCC patients (P < 0.01).
Conclusions
Claudin 10 protein is highly expressed in HCC tissue and is closely related to angiogenesis. Claudin 10 protein could be a useful marker to predict poor prognosis of HCC patients after hepatectomy.
Similar content being viewed by others
References
Aldred MA, Huang Y, Liyanarachchi S, Pellegata NS, Gimm O, Jhiang S, Davuluri RV, de la Chapelle A, Eng C (2004) Papillary and follicular thyroid carcinomas show distinctly different microarray expression profiles and can be distinguished by a minimum of five genes. J Clin Oncol 22(17):3531–3539
Cheung ST, Leung KL, Ip YC, Chen X, Fong DY, Ng IO, Fan ST, So S (2005) Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma. Clin Cancer Res 11(2 pt 1):551–556
Choi YL, Kim J, Kwon MJ, Choi JS, Kim TJ, Bae DS, Koh SS, In YH, Park YW, Kim SH, Ahn G, Shin YK (2007) Expression profile of tight junction protein claudin 3 and claudin 4 in ovarian serous adenocarcinoma with prognostic correlation. Histol Histopathol 22(11):1185–1195
Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C, Wong J (1999) Hepatectomy for hepatocellular carcinoma: toward zero hospital death. Ann Surg 229(3):322–330
He J, Gu D, Wu X, Reynolds K, Duan X, Yao C, Wang J, Chen CS, Chen J, Wildman RP, Klag MJ, Whelton PK (2005) Major causes of death among men and women in China. N Engl J Med 353(11):1124–1134
Huang GW, Yang LY (2002) Metallothionein expression in hepatocellular carcinoma and its clinical significance. World J Gastroenterol 8(4):650–653
Huang GW, Yang LY, Lu WQ (2005) Expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor in hepatocellular carcinoma: impact on neovascularization and survival. World J Gastroenterol 11(11):1705–1708
Huang GW, Tao YM, Ding X (2009) Endocan expression correlated with poor survival in human hepatocellular carcinoma. Dig Dis Sci 54(2):389–394
Hubert C, Sempoux C, Rahier J, Horsmans Y, Geubel A, Van Beers BE, Annet L, Zech F, Leonard D, Giqot JF (2007) Prognostic risk factors of survival after resection of hepatocellular carcinoma. Hepatogastroenterology 54(78):1791–1797
Ip YC, Cheung ST, Lee YT, Ho JC, Fan ST (2007) Inhibition of hepatocellular carcinoma invasion by suppression of claudin- 10 in HLE cells. Mol Cancer Ther 6(11):2858–2867
Li J, Chigurupati S, Agarwal R, Mughal MR, Mattson MP, Becker KG, Wood WH 3rd, Zhang Y, Morin PJ (2009) Possible angiogenic roles for claudin-4 in ovarian cancer. Cancer Biol Ther 8(19):1814–1822
Mann CD, Neal CP, Garcea G, Manson MM, Dennison AR, Berry DP (2007) Prognostic molecular markers in hepatocellular carcinoma: a systematic review. Eur J Cancer 43(6):979–992
Morita K, Tsukita S, Miyachi Y (2004) Tight junction-associated protein (occludin, ZO-1, claudin-1, claudin-4) in squamous cell carcinoma and Bowen’s disease. Br J Dermatol 151(2):328–334
Németh Z, Szász AM, Tátrai P, Németh J, Gyorffy H, Somorácz A, Szíjártó A, Kupcsulik P, Kiss A, Schaff Z (2009) Claudin-1, -2, -3, -4, -7, -8, and–10 protein expression in biliary tract cancers. J Histochem Cytochem 57(2):113–121
Nichols LS, Ashfaq R, Iacobuzio-Donahue CA (2004) Claudin 4 protein expression in primary and metastatic pancreatic caner: support for use as a therapeutic target. Am J Clin Pathol 121(2):226–230
Rangel LB, Agarwal R, D’Souza T, Pizer ES, Alò PL, Lancaster WD, Gregoire L, Schwartz DR, Cho KR, Morin PJ (2003) Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas. Clin Cancer Res 9(7):2567–2575
Resnick MB, Konkin T, Routhier J, Sabo E, Pricolo VE (2005) Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study. Mod Pathol 18(4):511–518
Sanada Y, Yoshida K, Itoh H (2007) Comparison of CT enhancement patterns and histologic features in hepatocellular carcinoma up to 2 cm: assessment of malignant potential with claudin-10 immunohistochemistry. Oncol Rep 17(5):1177–1182
Santin AD, Zhan F, Bellone S, Palmieri M, Cane S, Bignotti E, Anfossi S, Gokden M, Dunn D, Roman JJ, O’Brien TJ, Tian E, Cannon MJ, Shaughnessy J Jr, Pecorelli S (2004) Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: identification of candidate molecular markers for ovarian cancer diagnosis and therapy. Int J Cancer 112(1):14–25
Sherman M (2008) Recurrence of hepatocellular carcinoma. N Engl J Med 359(19):2045–2047
Sugita M, Geraci M, Gao B, Powell RL, Hirsch FR, Johnson G, Lapadat R, Gabrielson E, Bremnes R, Bunn PA, Franklin WA (2002) Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma. Cancer Res 62(14):3971–3979
Tokes AM, Kulka J, Paku S, Szik A, Páska C, Novák PK, Szilák L, Kiss A, Bögi K, Schaff Z (2005) Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Breast Cancer Res 7(2):R296–R305
Wang W, Yang LY, Huang GW, Lu WQ, Yang ZL, Yang JQ, Liu HL (2004) Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinoma with poor prognosis. Br J Cancer 90(12):2349–2355
Wang SM, Ooi LL, Hui KM (2007) Identification and validation of a novel gene signature associated with the recurrence of human hepatocellular carcinoma. Clin Cancer Res 13(21):6275–6283
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Huang, G.W., Ding, X., Chen, S.L. et al. Expression of claudin 10 protein in hepatocellular carcinoma: impact on survival. J Cancer Res Clin Oncol 137, 1213–1218 (2011). https://doi.org/10.1007/s00432-011-0987-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-011-0987-z