Elevated OCT1 participates in colon tumorigenesis and independently predicts poor prognoses of colorectal cancer patients.
Elevated OCT1 participates in colon tumorigenesis and independently predicts poor prognoses of colorectal cancer patients.
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OCT1 升高参与结肠肿瘤发生并独立预测结直肠癌患者的不良预后。
DOI：
10.1007/s13277-015-4080-0
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Wang XL
中科院分区：
文献类型：
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作者：
Wang YP;Song GH;Chen J;Xiao C;Li C;Zhong L;Sun X;Wang ZW;Deng GL;Yu FD;Xue YM;Tang HM;Peng ZH;Wang XL
八聚体转录因子1（Octamer transcription factor 1，OCT 1）被发现影响除结直肠癌（colorectal cancer，CRC）以外的许多癌症的发生和进展。本研究试图探讨OCT 1在结直肠癌中的作用，并阐明其表达与患者临床预后的关系。采用实时荧光定量PCR和免疫组化方法检测OCT 1在大肠癌组织和配对正常黏膜中的转录和转录后表达。此外，使用Cell Counting Kit-8测定、集落形成测定和小鼠致瘤性测定在体外和体内研究了OCT 1敲低对CRC细胞增殖的影响。OCT 1在结直肠癌中的表达升高。OCT 1的抑制在体外和体内均显著抑制CRC细胞增殖。OCT 1表达水平与N期、M期、美国癌症联合委员会（AJCC）分期（P = 0.027、0.014、0.002）及分化程度（P = 0.022）相关。通过使用多变量考克斯风险模型，OCT 1也被证明是一个独立预测总生存的因素（OS; P = 0.013，风险比= 2.747，95%置信区间1.125至3.715）和无病生存期（DFS; P = 0.004，风险比= 2.756，95%置信区间1.191至4.589）。我们的数据表明OCT 1在结直肠癌发生中具有重要作用，并作为一种新的预后指标和有希望的CRC抗癌治疗靶点。
Octamer transcription factor 1 (OCT1) was found to influence the genesis and progression of numerous cancers except for colorectal cancer (CRC). This study tried to explore the role of OCT1 in CRC and clarify the association between its expression and patients’ clinical outcome. Transcriptional and post-transcriptional expression of OCT1 was detected in CRC cancerous tissues and paired normal mucosae by real-time PCR as well as immunohistochemistry. Moreover, the effect of OCT1 knockdown on CRC cell proliferation was investigated both in vitro and in vivo using Cell Counting Kit-8 assay, colony-forming assay, and mouse tumorigenicity assay. Expression of OCT1 was found to be elevated in CRC. Suppression of OCT1 significantly inhibited CRC cell proliferation both in vitro and in vivo. Furthermore, upregulated level of OCT1 was significantly associated with N stage, M stage, and American Joint Committee on Cancer (AJCC) stage (P = 0.027, 0.014, and 0.002, respectively) as well as differential degree (P = 0.022). By using multivariate Cox hazard model, OCT1 was also shown to be a factor independently predicting overall survival (OS; P = 0.013, hazard ratio = 2.747, 95 % confidence interval 1.125 to 3.715) and disease-free survival (DFS; P = 0.004, hazard ratio = 2.756, 95 % confidence interval 1.191 to 4.589) for CRC patients. Our data indicate that OCT1 carries weight in colorectal carcinogenesis and functions as a novel prognostic indicator and a promising target of anti-cancer therapy for CRC.