Weng Jiawen, Zhang Yuqin, Liang Weijie, Xie Yuwen, Wang Kai, Xu Qian, Ding Yi, Li Yiyi
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Med Oncol. 2023 Jan 6;40(2):73. doi: 10.1007/s12032-022-01940-4.
Colorectal cancer (CRC) is the third leading malignancy worldwide in both new cases and deaths. Neoadjuvant radiotherapy is the standard preoperative regimens for locally advanced patients. However, approximately 50% of patients develop recurrence and metastasis after radiotherapy, which is largely due to the radiation resistance properties of the tumor, and the internal mechanism has not been elucidated. Here we found that CEMIP expression is up-regulated in a variety of tumor types, particularly in CRC. Public databases and clinical samples revealed that CEMIP expression is significantly higher in tumor tissues than in adjacent normal tissues in patients with locally advanced CRC who received neoadjuvant chemoradiotherapy, and it is closely related to the poor prognosis. Functional characterization uncovered that downregulation of CEMIP expression can enhance the radiosensitivity of CRC cells, which is confirmed to be achieved by promoting DNA damage and apoptosis. In vivo studies further verified that CEMIP knockdown can significantly improve the radiosensitivity of subcutaneously implanted colorectal tumors in mice, suggesting that CEMIP may be a radiation-resistant gene in CRC. Mechanistically, EGFR/PI3K/Akt signaling pathway is hypothesized to play a key role in CEMIP mediating radiation resistance. These results provide a potential new strategy targeting CEMIP gene for the comprehensive treatment of locally advanced CRC patients.
结直肠癌（CRC）在全球范围内无论是新发病例还是死亡人数方面都是第三大主要恶性肿瘤。新辅助放疗是局部晚期患者的标准术前治疗方案。然而，大约50%的患者在放疗后会出现复发和转移，这主要归因于肿瘤的放射抗性特性，其内在机制尚未阐明。在此，我们发现CEMIP在多种肿瘤类型中表达上调，尤其是在结直肠癌中。公共数据库和临床样本显示，在接受新辅助放化疗的局部晚期结直肠癌患者中，肿瘤组织中CEMIP的表达明显高于相邻正常组织，且与预后不良密切相关。功能特性研究发现，CEMIP表达下调可增强结直肠癌细胞的放射敏感性，这被证实是通过促进DNA损伤和凋亡来实现的。体内研究进一步证实，敲低CEMIP可显著提高小鼠皮下植入的结直肠肿瘤的放射敏感性，提示CEMIP可能是结直肠癌中的一个放射抗性基因。从机制上讲，推测EGFR/PI3K/Akt信号通路在CEMIP介导的放射抗性中起关键作用。这些结果为局部晚期结直肠癌患者的综合治疗提供了一种潜在的靶向CEMIP基因的新策略。
