Upregulation of COL6A1 is predictive of poor prognosis in clear cell renal cell carcinoma patients.
Upregulation of COL6A1 is predictive of poor prognosis in clear cell renal cell carcinoma patients.
复制标题
COL6A1 的上调预示着透明细胞肾细胞癌患者的预后不良。
DOI：
10.18632/oncotarget.4860
复制
发表时间：
2015-09-29
期刊：
影响因子：
--
通讯作者：
Ye D
中科院分区：
文献类型：
--
作者：
Wan F;Wang H;Shen Y;Zhang H;Shi G;Zhu Y;Dai B;Ye D
背景：细胞外基质（extracellular matrix，ECM）在肿瘤的发生、发展中起重要作用。胶原VI是一种重要的ECM蛋白。在这项研究中，我们研究了编码胶原VI α1多肽的COL 6A 1基因在参与肾透明细胞癌（ccRCC）进展和结局的生物学功能中的潜在作用。材料与方法：共纳入288例在复旦大学附属肿瘤医院（FUSCC）接受根治性肾切除术（RN）或保留肾单位肾切除术（NSS）的ccRCC患者。从FUSCC组织库获得的冷冻样品中提取总RNA，并通过qRT-PCR测定COL 6A 1的表达。分析COL 6A 1表达与ccRCC预后的临床关系。然后在癌症基因组图谱（TCGA）队列中验证这些数据。我们还研究了COL 6A 1过表达在裸鼠体内异种移植肿瘤模型中的作用。结果如下：在TCGA队列的多变量分析中，COL 6A 1高表达预测ccRCC患者的总生存期（OS）（HR：2.588 95%CI 1.616-4.146）和无病生存期（DFS）（HR：3.106 95%CI 1.534-6.288）的预后不良。在FUSCC队列中，校正相关因素后，COL 6A 1表达表明ccRCC患者的OS（HR 2.211; 95%CI，1.360-8.060）和DFS（HR 3.052; 95%CI，1.500-6.210）预后不良。COL 6A 1过表达促进异种移植裸鼠的肿瘤生长。结论：ccRCC患者COL 6A 1表达增加与预后不良相关。此外，COL 6A 1在体内刺激肿瘤生长。
Background: The extracellular matrix (ECM) is reported to play an important role in tumorigenesis and progression. Collagen VI is an important ECM protein. In this study, we investigated the potential role of the COL6A1 gene, which encodes the α1 polypeptide of collagen VI, in the biological functions involved in the progression and outcome of clear cell renal cell carcinoma (ccRCC). Materials and methods: A total of 288 ccRCC patients who underwent radical nephrectomy (RN) or nephron sparing nephrectomy (NSS) at Fudan University Shanghai Cancer Center (FUSCC) were enrolled. Total RNA was extracted from frozen samples obtained from the tissue bank of FUSCC and expression of COL6A1 was determined by qRT-PCR. The clinical relationship between COL6A1 expression and ccRCC prognosis was analyzed. These data were then validated in the Cancer Genome Atlas (TCGA) cohort. We also investigated the effect of COL6A1 overexpression in a xenografted tumor model in nude mice in vivo. Results: In multivariate analysis of TCGA cohorts, COL6A1 high expression was predictive of poor prognosis in ccRCC patients’ overall survival (OS) (HR: 2.588 95%CI 1.616–4.146) and disease free survival(DFS) (HR: 3.106 95%CI 1.534–6.288). In FUSCC cohorts, after adjusted for relevant factors, the COL6A1 expression indicates poor prognosis in ccRCC patients’s OS (HR 2.211; 95% CI, 1.360–8.060) and DFS (HR 3.052; 95%CI, 1.500–6.210). COL6A1 overexpression promoted tumor growth in xenografted nude mice. Conclusion: Increased COL6A1 expression correlates with poor prognosis in ccRCC patients. Moreover, COL6A1 stimulates tumor growth in vivo.