Ke Ai-Wu, Shi Guo-Ming, Zhou Jian, Wu Fei-Zhen, Ding Zhen-Bin, Hu Mei-Yu, Xu Yang, Song Zheng-Ji, Wang Zhi-Jun, Wu Jin-Cai, Bai Dou-Sheng, Li Jia-Chu, Liu Kang-Da, Fan Jia
Experimental Research Center of Zhongshan Hospital, Fudan University, Shanghai, PR China.
Hepatology. 2009 Feb;49(2):491-503. doi: 10.1002/hep.22639.
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.
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.
据报道，四跨膜蛋白CD151在多种肿瘤中作为转移的促进因子，并且在c-Met/肝细胞生长因子信号传导中起重要作用。然而，CD151单独以及CD151/c-Met在肝细胞癌（HCC）中的共表达作用仍不清楚。我们发现CD151的表达与HCC细胞系的转移潜能呈正相关，用高表达CD151（CD151(high)）修饰的细胞在体外显示出更高的基质金属蛋白酶9分泌和侵袭性，在体内具有更高的转移能力。此外，伴有血管侵犯、肿瘤体积大、多肿瘤、高肿瘤-淋巴结-转移分期以及未分化肿瘤的HCC患者倾向于具有更高的CD151表达。CD151(high)的HCC患者术后3年、5年和7年的总生存率（OS）显著低于CD151(low)组患者，相应地，CD151(high)的HCC患者的累积复发率显著高于CD151(low)组。与相邻的非肿瘤和正常肝组织相比，CD151和c-Met在HCC中均显著过表达。Pearson相关性分析显示HCC中CD151与c-Met之间存在轻微相关性。重要的是，CD151(high)/c-Met(high)患者的5年和7年OS率分别为50.5%和37.8%，显著低于CD151(low)/c-Met(low)患者（分别为63.9%和54.6%）。CD151(high)/c-Met(high)患者的5年和7年累积复发率分别为53.3%和71.9%，明显高于CD151(low)/c-Met(low)患者（分别为39.0%和52.5%）。多因素分析显示CD151以及CD151/c-Met的组合是OS和累积复发的独立预后指标。
CD151与HCC的侵袭性呈正相关，CD151或CD151/c-Met的组合是预测HCC预后的新型标志物和潜在治疗靶点。
