Dong Weiwei, Cui Jiantao, Yang Jingwen, Li Wenmei, Wang Shuo, Wang Xiaojuan, Li Xing, Lu Youyong, Xiao Wenhua
Department of Oncology, The First Affiliated Hospital, General Hospital of Chinese People's Liberation Army, Beijing 100048, China.
Department of Oncology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
Discov Med. 2015 Dec;20(112):357-67.
The Rab27 subfamily of secretory small GTPase plays a vital role in vesicle trafficking and regulates tumor growth and metastasis in several cancer types. Thus, this research was designed to explore the clinical and prognostic significance of Rab27A and Rab27B in colorectal cancer (CRC) patients. Reverse transcription-polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry (IHC) analysis were used to examine Rab27A and Rab27B expression in human CRC cell lines and primary tumors. The correlation of gene expression with clinicopathological features and prognosis was also evaluated. Our results indicated that Rab27A expression was down-regulated in primary tumors compared with matched adjacent tissues (100%, 8/8), as detected by western blot. IHC analysis revealed that the positive expression rate of Rab27A in primary CRC tissues was lower than in adjacent normal tissues (P = 0.005). Negative expression of Rab27A and Rab27B significantly correlated with poor tumor differentiation (both P < 0.001) and positive vascular invasion (P = 0.005, P = 0.021, respectively). Moreover, absence of Rab27A was associated with advanced tumor node metastasis (TNM) stage (P = 0.006), distant metastasis (P = 0.002), and local recurrence (P = 0.038). Survival analysis also showed a significant correlation between unfavorable survival and negative expression of Rab27A (P = 0.002). In addition, positive expression of both Rab27A and Rab27B was a protective factor in CRC. In conclusion, decreased expression of Rab27A and Rab27B, especially Rab27A, closely correlated with tumor progression and are valuable prognostic indicators in CRC patients.
分泌型小GTP酶的Rab27亚家族在囊泡运输中起着至关重要的作用，并在几种癌症类型中调节肿瘤的生长和转移。因此，本研究旨在探讨Rab27A和Rab27B在结直肠癌（CRC）患者中的临床及预后意义。采用逆转录聚合酶链反应（RT-PCR）、蛋白质印迹法和免疫组织化学（IHC）分析检测Rab27A和Rab27B在人CRC细胞系和原发性肿瘤中的表达。还评估了基因表达与临床病理特征及预后的相关性。我们的结果表明，通过蛋白质印迹法检测，与配对的相邻组织相比，原发性肿瘤中Rab27A的表达下调（100%，8/8）。IHC分析显示，原发性CRC组织中Rab27A的阳性表达率低于相邻正常组织（P = 0.005）。Rab27A和Rab27B的阴性表达与肿瘤低分化显著相关（均P < 0.001）和血管侵犯阳性（分别为P = 0.005，P = 0.021）。此外，Rab27A缺失与肿瘤淋巴结转移（TNM）晚期（P = 0.006）、远处转移（P = 0.002）和局部复发（P = 0.038）相关。生存分析还显示，Rab27A阴性表达与不良生存之间存在显著相关性（P = 0.002）。此外，Rab27A和Rab27B的阳性表达是CRC的一个保护因素。总之，Rab27A和Rab27B表达降低，尤其是Rab27A，与肿瘤进展密切相关，是CRC患者有价值的预后指标。
