Role of Overexpression of CD151 and/or c-Met in Predicting Prognosis of Hepatocellular Carcinoma
Role of Overexpression of CD151 and/or c-Met in Predicting Prognosis of Hepatocellular Carcinoma
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DOI：
10.1002/hep.22639
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发表时间：
2009-02-01
期刊：
影响因子：
13.5
通讯作者：
Fan, Jia
中科院分区：
文献类型：
--
作者：
Ke, Ai-Wu;Shi, Guo-Ming;Fan, Jia
据报道，四跨膜蛋白 CD151 在多种肿瘤中充当转移促进剂，并在 c-Met/肝细胞生长因子信号传导中发挥重要作用。然而，CD151单独和CD151/c-Met共表达在肝细胞癌（HCC）中的作用仍不清楚。我们发现了CD151的表达。与HCC细胞系的转移潜能呈正相关，并且CD151（高）修饰的细胞在体外表现出更高的基质金属蛋白酶9分泌和侵袭性，在体内表现出更高的转移能力。此外，血管侵犯、肿瘤较大、肿瘤多发、肿瘤淋巴结转移分期高、肿瘤未分化的HCC患者CD151表达较高。 CD151（高）HCC患者术后3、5、7年总生存（OS）显着低于CD151（低）组，相应累积复发率显着高于CD151（低）组。与邻近的非肿瘤和正常肝组织相比，CD151 和 c-Met 在 HCC 中显着过度表达。 Pearson 相关分析显示 HCC 中 CD151 和 c-Met 之间存在轻微相关性。重要的是，CD151（高）/c-Met（高）患者的5年和7年OS率分别为50.5％和37.8％，显着低于CD151（低）/c-Met（低）患者的5年和7年OS率（分别为63.9％和54.6％）。 CD151(高)/c-Met(高)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(低)/c-Met(低)患者的5年和7年累积复发率(分别为39.0%和52.5%)。多变量分析显示CD151。 CD151/c-Met 和 CD151/c-Met 组合是 OS 和累积复发的独立预后指标。结论：CD151与HCC的侵袭性呈正相关，CD151或CD151/c-Met联合是预测HCC预后的新标志物和潜在的治疗靶点。 （肝病学 2009；49：491-503。）
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.)