2. Academic Validation
  3. 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

  • Cell Death Dis. 2022 May 6;13(5):439. doi: 10.1038/s41419-022-04885-8.
Wen-Juan Ma  # 1 2 3,  Yukun Chen  # 4,  Jian-Hong Peng  # 1 2 5,  Chaoming Tang  # 6,  Ling Zhang 1 2 7,  Min Liu 1 2 8,  Shanshan Hu 9,  Haineng Xu 10,  Hua Tan 11,  Yangkui Gu 12,  Zhi-Zhong Pan 1 2 5,  Gong Chen 13 14 15,  Zhong-Guo Zhou 16 17 18,  Rong-Xin Zhang 19 20 21
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong Province, People's Republic of China.
  • 2 Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, Guangdong Province, People's Republic of China.
  • 3 Intensive Care Unit Department, Sun Yat-Sen University Cancer Centre, Guangzhou, 510060, Guangdong Province, People's Republic of China.
  • 4 Zhongshan School of Medicine, Sun Yat-Sen University, No. 74, Zhongshan Rd. 2, Guangzhou, 510080, Guangdong Province, People's Republic of China.
  • 5 Department of Colorectal Surgery, Sun Yat-Sen University Cancer Centre, Guangzhou, 510060, Guangdong Province, People's Republic of China.
  • 6 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, QingYuan, Guangdong Province, People's Republic of China.
  • 7 Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China.
  • 8 Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China.
  • 9 Department of Statistics, Rutgers University, New Brunswick, NJ, 08854, USA.
  • 10 Ovarian Cancer Research Center, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • 11 School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • 12 Intervention Department, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China.
  • 13 State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong Province, People's Republic of China. chengong@sysucc.org.cn.
  • 14 Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, Guangdong Province, People's Republic of China. chengong@sysucc.org.cn.
  • 15 Department of Colorectal Surgery, Sun Yat-Sen University Cancer Centre, Guangzhou, 510060, Guangdong Province, People's Republic of China. chengong@sysucc.org.cn.
  • 16 State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong Province, People's Republic of China. zhouzhg@sysucc.org.cn.
  • 17 Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, Guangdong Province, People's Republic of China. zhouzhg@sysucc.org.cn.
  • 18 Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China. zhouzhg@sysucc.org.cn.
  • 19 State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong Province, People's Republic of China. zhangrx@sysucc.org.cn.
  • 20 Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, Guangdong Province, People's Republic of China. zhangrx@sysucc.org.cn.
  • 21 Department of Colorectal Surgery, Sun Yat-Sen University Cancer Centre, Guangzhou, 510060, Guangdong Province, People's Republic of China. zhangrx@sysucc.org.cn.
  • # Contributed equally.
PMID: 35523764 DOI: 10.1038/s41419-022-04885-8
Abstract

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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