Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma

Abstract

It has been reported that tetraspanin CD151 acts as a promoter of metastasis in several tumors and plays an important role in c-Met/hepatocyte growth factor signaling. However, the role of CD151 alone and coexpression of CD151/c-Met in hepatocellular carcinoma (HCC) remains unclear. We found that expression of CD151 was positively related to metastatic potential of HCC cell lines, and modified cells with CD151 high showed higher secretion of matrix metalloproteinase 9 and aggressiveness in vitro and higher metastatic ability in vivo. Furthermore, HCC patients with vascular invasion, large tumors, multiple tumors, high tumor-node-metastasis stage, and undifferentiated tumor were prone to have higher CD151 expression. The postoperative 3-, 5-, and 7-year overall survival (OS) of patients in HCCs with CD151 high were significantly lower than those in the CD151 low group, and correspondingly cumulative recurrence rates in HCCs with CD151 high were significantly higher than those in the CD151 low group. Both CD151 and c-Met were remarkably overexpressed in HCCs, compared with adjacent nontumorous and normal liver tissues. Pearson correlation analysis showed a slight correlation between CD151 and c-Met in HCCs. Importantly, the 5-and 7-year OS rates in CD151 high /c-Met high patients were 50.5% and 37.8%, respectively, significantly lower than those of CD151 low /c-Met low patients (63.9% and 54.6%, respectively). Five-and 7-year cumulative recurrence rates in CD151 high /c-Met high patients were 53.3% and 71.9%, respectively, markedly higher than those of CD151 low / c-Met low patients (39.0% and 52.5%, respectively). Multivariate analysis revealed that CD151 and combination of CD151/c-Met were independent prognostic indicators for OS and cumulative recurrence. Conclusion: CD151 is positively associated with invasiveness of HCC, and CD151 or combination of CD151/c-Met is a novel marker in predicting the prognosis of HCC and a potential therapeutic target. (HEPATOLOGY 2009;49:491-503.)

Preclinical Evaluation of AMG 337, a Highly Selective Small Molecule MET Inhibitor, in Hepatocellular Carcinoma

“…Many studies have reported on the association between alterations in MET and poor prognosis and/or disease severity in human cancers (25)(26)(27)(28). These findings support the hypothesis that specific alterations in MET may provide predictive capacity for identifying patients most likely to benefit from MET inhibitor therapy.…”

“…In addition, the HGF/MET signaling pathway has been shown to be activated during the genesis and progression of hepatocellular carcinoma. Many reports have highlighted the prevalence of MET gene and protein expression in hepatocellular carcinoma, and have investigated the role of MET signaling in hepatocellular carcinoma progression and maintenance (24)(25)(26)(27)(28). The importance of MET signaling in these processes suggests that the status of MET gene amplification and/or protein expression in patients with hepatocellular carcinoma may serve as potential biomarkers for prognosis or response to anti-HGF/MET therapy.…”

CD151 modulates expression of matrix metalloproteinase 9 and promotes neoangiogenesis and progression of hepatocellular carcinoma

“…4 CD151, one of the most important of the tetraspanins, has been extensively studied, especially in connection with the progression and prognosis of malignant tumors, including breast cancer, colon cancer, prostate cancer, and HCC. [5][6][7][8] Initial evidence for the involvement of CD151 in metastasis came from a study that showed specific in vivo inhibition of metastasis in a human epidermoid carcinoma by an unknown antibody. Since then, reduction of CD151 expression in primary melanocytes by small interfering RNA (siRNA) has been shown to result in the loss of motility, whereas it has little effect on the steady-state levels of integrins.…”

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.…”