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Evaluation of A 55-Gene Classifier As A Prognostic Biomarker for Adjuvant Chemotherapy in Stage III Colon Cancer Patients

Evaluation of A 55-Gene Classifier As A Prognostic Biomarker for Adjuvant Chemotherapy in Stage III Colon Cancer Patients

Authors :
Seiji Hasegawa
Shigeki Yamaguchi
Eiji Shinto
Naohiro Tomita
Megumi Ishiguro
Yasumasa Takii
Kazuo Hase
Hideyuki Ishida
Yojiro Hashiguchi
Eiji Oki
Tetsuya Kusumoto
Shinobu Ohnuma
Mototsugu Shimokawa
Masaru Morita
Heita Ozawa
Masafumi Tanaka
Sachiyo Tada
Tomoko Matsushima
Manabu Shiozawa
Source :
BMC Cancer, Vol 21, Iss 1, Pp 1-10 (2021), BMC Cancer
Publication Year :
2021
Publisher :
Research Square Platform LLC, 2021.

Abstract

Background Adjuvant 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. Methods We 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. Results Among 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. Conclusions Subclassification 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 registration The study protocol was registered in the University Hospital Medical Education Network (UMIN) clinical trial registry (UMIN study ID: 000023879).

Details

Database :
OpenAIRE
Journal :
BMC Cancer, Vol 21, Iss 1, Pp 1-10 (2021), BMC Cancer
Accession number :
edsair.doi.dedup.....a80f16a9fa8d66da69492b5f902eba59
Full Text :
https://doi.org/10.21203/rs.3.rs-579197/v1