Overexpression of CD151 as an adverse marker for intrahepatic cholangiocarcinoma patients

Abstract

BACKGROUND:Previous studies have indicated that CD151, a hydrophobic protein, forms a functional complex with the proto‐oncogene that encodes an N‐methyl‐N′‐nitro‐N‐nitroso‐guanidine (MET) protein (c‐Met), and CD151 overexpression reportedly is involved in metastasis/invasion of several tumors. The objective of the current study was to investigate the expression and role of CD151 and/or c‐Met in intrahepatic cholangiocarcinoma (ICC).METHODS:Sixty ICC tissues with matched nontumorous tissues and 20 normal liver tissues were used to analyze CD151 expression at the level of messenger RNA (mRNA) and protein. Then, the expression of CD151 in an ICC cell line was interrupted using a specific lentiviral‐mediated small hairpin RNA (shRNA)‐CD151, and the role of CD151 in the proliferation, metastasis, and invasion of ICC cells was assessed. The expression of CD151/c‐Met was examined further by immunohistochemistry in a tissue microarray (TMA) that included 140 samples of ICC, and the prognostic role of CD151 and/or c‐Met in ICC was evaluated in Kaplan‐Meier and Cox regression analyses.RESULTS:The expression of CD151 in ICC tissues was much higher than that in nontumorous samples and normal liver; and, after the down‐regulation of CD151, HCCC‐9810 cells had decreased capability for metastasis/invasion in vitro. CD151 overexpression was correlated significantly with larger tumors, poor differentiation, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (P<.05). The postoperative 2‐year and 5‐year overall survival (OS) rates for patients with low CD151 expression (<50% tumor staining) and/or low c‐Met expression (<20% tumor staining) were higher than the rates for patients with high CD151 expression (≥50% tumor staining) and/or high c‐Met expression (≥20% tumor staining). Multivariate analysis revealed that CD151 overexpression and c‐Met overexpression were independent prognostic markers for ICC.CONCLUSIONS:Overexpression of CD151 was implicated in metastasis/invasion of ICC, and both CD151 overexpression and c‐Met overexpression may be potential molecular therapeutic targets for ICC. Cancer 2010. © 2010 American Cancer Society.

Is c-Met oncoprotein expression an adverse prognosticator in extrahepatic bile duct cancer treated with curative resection followed by adjuvant chemoradiotherapy?

“…Previous studies of c-Met expression in bile duct cancer reported broad range of positivity; 12-58 % in IHBD cancer, and 0-68 % in EHBD cancer [4,[13][14][15][16][17]23]. As Miyamoto et al [17] interpreted, this was probably attributed to the small numbers of cases studied, or to differences in the definition of positivity.…”

“…As the molecular mechanism of carcinogenesis has been better understood recently, receptor tyrosine kinases, such as mesenchymal-epithelial transition factor (c-Met), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF), have emerged as prognostic factors or promising targets for treatment in bile duct cancer [2][3][4]. c-Met is a transmembrane receptor tyrosine kinase, and binds with high affinity to its only known ligand, the hepatocyte growth factor (HGF).…”

“…HGF binding to c-Met activates downstream signaling pathways that have been implicated in the invasion and migration of cancer cells [5]. Expression of c-Met protein has been reported in various primary tumors such as head and neck [6], breast [7], lung [8], stomach [9], esophagus [10], colon [11], liver [12], and bile duct cancers [4,[13][14][15][16][17]. Most studies regarding these various malignancies have suggested the possibility that c-Met expression was associated with worse prognosis.…”

CD151 in cancer progression and metastasis: a complex scenario

“…Clinically, high levels of CD151 are correlated with poor prognosis in a variety of tumours including epithelial malignancies such as carcinomas of the lung, 68 breast (invasive ductal carcinoma), 34,53,69 colon, 70 pancreas, 71 kidney, 10 prostate (PCa), 72 liver 73,74 and oesophagus (SCC), 75 as well as glioblastoma. 76 As in most cancers an elevated level of CD151 expression is associated positively with a high tumour grade (Table 1), the assumption that CD151 is involved in cancer progression is well grounded.…”

“…Indeed, overexpression of CD151 at the primary site was found to correspond with the development of metastases, mostly in lymph nodes. 53,71,[73][74][75] Formation of secondary tumours in distant organs such as lungs and bone was also noted in clear cell renal carcinoma (RCC). 10 CD151 is implicated as a potential diagnostic marker in osteosarcoma and prostate cancer.…”