State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong Province, People's Republic of China.
Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, Guangdong Province, People's Republic of China.
Cell Death Dis. 2022 May 6;13(5):439. doi: 10.1038/s41419-022-04885-8.
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.
根据 EPOC 研究，化疗可使 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。通过免疫组织化学评估了 181 例 IV 期结肠癌患者的 DENND2D 表达。DENND2D 表达的患者预后优于 DENND2D 无表达的患者（5 年总生存率 [OS]：42%比 12%，p=0.038；5 年无病生存率：20%比 10%，p=0.001）。DENND2D 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）。DENND2D 在体外和体内抑制 CRC 增殖。DENND2D 的下调也促进了体内远处器官的转移。在机制上，DENND2D 抑制了 CRC 中的 MAPK 通路。DENND2D 阴性的结肠癌患者预后总是较差，并且更有可能从新辅助化疗中受益。DENND2D 可能是 IV 期结肠癌的一个新的预后因素和新辅助化疗需求的预测因子。
