Stage IV colon cancer patients without DENND2D expression benefit more from neoadjuvant chemotherapy.
Stage IV colon cancer patients without DENND2D expression benefit more from neoadjuvant chemotherapy.
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DOI：
10.1038/s41419-022-04885-8
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发表时间：
2022-05-06
影响因子：
9
通讯作者：
Zhang, Rong-xin
中科院分区：
文献类型：
--
作者：
Ma, Wen-juan;Chen, Yukun;Peng, Jian-hong;Tang, Chaoming;Zhang, Ling;Liu, Min;Hu, Shanshan;Xu, Haineng;Tan, Hua;Gu, Yangkui;Pan, Zhi-zhong;Chen, Gong;Zhou, Zhong-guo;Zhang, Rong-xin
根据EPOC研究，化疗可以将IV期结肠癌患者的5年无病生存率提高8.1%。然而，需要更多的分子生物标志物来识别需要新辅助化疗的患者。通过免疫组织化学方法评估181例IV期结肠癌患者中DEND 2D的表达。DEND 2D表达患者的预后优于无DEND 2D表达患者（5年总生存率[OS]：42% vs. 12%，p = 0.038; 5年无病生存率：20% vs. 10%，p = 0.001）。DEND 2D阴性组的亚组分析显示，接受新辅助化疗的患者的OS长于未接受新辅助化疗的患者（RR = 0.179; 95% CI = 0.054-0.598; p = 0.003）。DEND 2D在体外和体内抑制CRC增殖。DEND 2D的下调也促进了体内远处器官的转移。在机制上，DEND 2D抑制CRC中的MAPK通路。DEND 2D阴性的结肠癌患者总是表现出更差的预后，更有可能从新辅助化疗中获益。DEND 2D可能是一个新的预后因子，并预测IV期结肠癌是否需要新辅助化疗。
According to the EPOC study, chemotherapy could improve 5-year disease-free survival of stage IV colon cancer patients by 8.1%. However, more molecular biomarkers are required to identify patients who need neoadjuvant chemotherapy. DENND2D expression was evaluated by immunohistochemistry in 181 stage IV colon cancer patients. The prognosis was better for patients with DENND2D expression than patients without DENND2D expression (5-year overall survival [OS]: 42% vs. 12%, p = 0.038; 5-year disease-free survival: 20% vs. 10%, p = 0.001). Subgroup analysis of the DENND2D-negative group showed that patients treated with neoadjuvant chemotherapy achieved longer OS than patients without neoadjuvant chemotherapy (RR = 0.179; 95% CI = 0.054–0.598; p = 0.003). DENND2D suppressed CRC proliferation in vitro and in vivo. Downregulation of DENND2D also promoted metastasis to distant organs in vivo. Mechanistically, DENND2D suppressed the MAPK pathway in CRC. Colon cancer patients who were DENND2D negative always showed a worse prognosis and were more likely to benefit from neoadjuvant chemotherapy. DENND2D may be a new prognostic factor and a predictor of the need for neoadjuvant chemotherapy in stage IV colon cancer.
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影响因子：
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