Wan Fangning, Wang Hongkai, Shen Yijun, Zhang Hailiang, Shi Guohai, Zhu Yao, Dai Bo, Ye Dingwei
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Oncotarget. 2015 Sep 29;6(29):27378-87. doi: 10.18632/oncotarget.4860.
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).
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.
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.
Increased COL6A1 expression correlates with poor prognosis in ccRCC patients. Moreover, COL6A1 stimulates tumor growth in vivo.
据报道，细胞外基质（ECM）在肿瘤发生和进展中起重要作用。胶原蛋白VI是一种重要的细胞外基质蛋白。在本研究中，我们调查了编码胶原蛋白VI的α1多肽的COL6A1基因在透明细胞肾细胞癌（ccRCC）进展和预后相关生物学功能中的潜在作用。
招募了288例在复旦大学附属肿瘤医院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。从复旦大学附属肿瘤医院组织库获取的冷冻样本中提取总RNA，通过qRT-PCR检测COL6A1的表达。分析COL6A1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。我们还在体内裸鼠异种移植肿瘤模型中研究了COL6A1过表达的影响。
在TCGA队列的多因素分析中，COL6A1高表达预示ccRCC患者总生存期（OS）预后不良（HR：2.588，95%CI 1.616 - 4.146）和无病生存期（DFS）预后不良（HR：3.106，95%CI 1.534 - 6.288）。在复旦大学附属肿瘤医院队列中，校正相关因素后，COL6A1表达提示ccRCC患者OS预后不良（HR 2.211；95%CI，1.360 - 8.060）和DFS预后不良（HR 3.052；95%CI，1.500 - 6.210）。COL6A1过表达促进了裸鼠异种移植肿瘤的生长。
COL6A1表达增加与ccRCC患者预后不良相关。此外，COL6A1在体内刺激肿瘤生长。
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