Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients

BMC Cancer

Mototsugu Shimokawa¹  Masafumi Tanaka²  Manabu Shiozawa³  Heita Ozawa⁴  Hideyuki Ishida⁵  Tetsuya Kusumoto⁶  Yasumasa Takii⁷  Shigeki Yamaguchi⁸  Eiji Oki⁹  Naohiro Tomita^1,10  Kazuo Hase^1,11  Eiji Shinto^1,11  Seiji Hasegawa^1,12  Yojiro Hashiguchi^1,13  Shinobu Ohnuma^1,14  Megumi Ishiguro^1,15  Masaru Morita^1,16  Sachiyo Tada^1,17  Tomoko Matsushima^1,17 

[1] Clinical Research Institute, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan;Coloproctology Center, Takano Hospital, Kumamoto, Japan;Colorectal Surgery Division, Kanagawa Cancer Center, Yokohama, Japan;Department of Colorectal Surgery, Tochigi Cancer Center, Utsunomiya, Japan;Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan;Department of Gastroenterological Surgery, Clinical Research Center, Cancer Research Division, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan;Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, Niigata, Japan;Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Japan;Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan;Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan;Department of Surgery, National Defense Medical College, Tokorozawa, Japan;Department of Surgery, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japan;Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan;Department of Surgery, Tohoku University Hospital, Sendai, Japan;Department of Translational Oncology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan;Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan;LS Business, Sysmex Corporation, Kobe, Japan;

关键词: Colon cancer;    Predictive;    Adjuvant chemotherapy;    Oxaliplatin;    Subtyping;   

DOI  :  10.1186/s12885-021-09088-6

来源: Springer

【 摘 要 】

BackgroundAdjuvant chemotherapy reduces the risk of recurrence of stage III colon cancer (CC). However, more effective prognostic and predictive biomarkers are needed for better treatment stratification of affected patients. Here, we constructed a 55-gene classifier (55GC) and investigated its utility for classifying patients with stage III CC.MethodsWe retrospectively identified patients aged 20–79 years, with stage III CC, who received adjuvant chemotherapy with or without oxaliplatin, between the years 2009 and 2012.ResultsAmong 938 eligible patients, 203 and 201 patients who received adjuvant chemotherapy with and without oxaliplatin, respectively, were selected by propensity score matching. Of these, 95 patients from each group were analyzed, and their 5-year relapse-free survival (RFS) rates with and without oxaliplatin were 73.7 and 77.1%, respectively. The hazard ratios for 5-year RFS following adjuvant chemotherapy (fluoropyrimidine), with and without oxaliplatin, were 1.241 (95% CI, 0.465–3.308; P = 0.67) and 0.791 (95% CI, 0.329–1.901; P = 0.60), respectively. Stratification using the 55GC revealed that 52 (27.3%), 78 (41.1%), and 60 (31.6%) patients had microsatellite instability (MSI)-like, chromosomal instability (CIN)-like, and stromal subtypes, respectively. The 5-year RFS rates were 84.3 and 72.0% in patients treated with and without oxaliplatin, respectively, for the MSI-like subtype (HR, 0.495; 95% CI, 0.145–1.692; P = 0.25). No differences in RFS rates were noted in the CIN-like or stromal subtypes. Stratification by cancer sidedness for each subtype showed improved RFS only in patients with left-sided primary cancer treated with oxaliplatin for the MSI-like subtype (P = 0.007). The 5-year RFS rates of the MSI-like subtype in left-sided cancer patients were 100 and 53.9% with and without oxaliplatin, respectively.ConclusionsSubclassification using 55GC and tumor sidedness revealed increased RFS in patients within the MSI-like subtype with stage III left-sided CC treated with fluoropyrimidine and oxaliplatin compared to those treated without oxaliplatin. However, the predictive power of 55GC subtyping alone did not reach statistical significance in this cohort, warranting larger prospective studies.Trial registrationThe study protocol was registered in the University Hospital Medical Education Network (UMIN) clinical trial registry (UMIN study ID: 000023879).

【 授权许可】

CC BY