Lai Er-Yong, Chen Zhen-Guo, Zhou Xuan, Fan Xiao-Rong, Wang Hua, Lai Ping-Lin, Su Yong-Chun, Zhang Bai-Yu, Bai Xiao-Chun, Li Yun-Feng
The Clinical Research Center for Colorectal Tumor, The Third Affiliated Hospital of Kunming Medical University, Kunming, China E-mail :
Asian Pac J Cancer Prev. 2014;15(11):4589-94. doi: 10.7314/apjcp.2014.15.11.4589.
The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.
雷帕霉素哺乳动物靶蛋白（mTOR）信号通路在包括结直肠癌（CRC）在内的多种癌症发病机制中上调。DEPTOR是一种mTOR抑制剂，其表达受mTOR负调控。然而，DEPTOR在CRC发生发展中的作用尚不清楚。本研究旨在调查一部分CRC患者中DEPTOR的表达及mTORC1活性（P-S6），并确定它们与肿瘤分化、侵袭、淋巴结转移及无病生存期的关系。在此，通过组织芯片对90例CRC患者的1.5毫米肿瘤组织芯及90例相邻正常黏膜样本进行P-S6（S235/236）和DEPTOR的免疫组化表达评估。P-S6（S235/236）在CRC中表达上调，CRC中P-S6（S235/236）的阳性率（63.3%）显著高于对照组织（36.7%，30%）（p<0.05）。P-S6（S235/236）还与高肿瘤组织学分级（p=0.002）及阳性淋巴结转移（p=0.002）相关。相反，DEPTOR的表达水平与低肿瘤组织学分级（p=0.006）及阴性淋巴结转移（p=0.001）相关。有趣的是，CRC中P-S6（S235/236）表达与DEPTOR表达呈显著负相关（p=0.011，R = -0.279）。然而，CRC中P-S6（S235/236）上调（p=0.693）及DEPTOR下调（p=0.331）与总生存期无显著关联。因此，我们得出结论，DEPTOR的表达与CRC中的mTORC1活性及肿瘤进展呈负相关。DEPTOR是预后评估的潜在标志物及CRC治疗的靶点。
