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

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 uti...

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Autores principales: Oki, Eiji, Shinto, Eiji, Shimokawa, Mototsugu, Yamaguchi, Shigeki, Ishiguro, Megumi, Hasegawa, Seiji, Takii, Yasumasa, Ishida, Hideyuki, Kusumoto, Tetsuya, Morita, Masaru, Tomita, Naohiro, Shiozawa, Manabu, Tanaka, Masafumi, Ozawa, Heita, Hashiguchi, Yojiro, Ohnuma, Shinobu, Tada, Sachiyo, Matsushima, Tomoko, Hase, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672629/
https://www.ncbi.nlm.nih.gov/pubmed/34906120
http://dx.doi.org/10.1186/s12885-021-09088-6
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author Oki, Eiji
Shinto, Eiji
Shimokawa, Mototsugu
Yamaguchi, Shigeki
Ishiguro, Megumi
Hasegawa, Seiji
Takii, Yasumasa
Ishida, Hideyuki
Kusumoto, Tetsuya
Morita, Masaru
Tomita, Naohiro
Shiozawa, Manabu
Tanaka, Masafumi
Ozawa, Heita
Hashiguchi, Yojiro
Ohnuma, Shinobu
Tada, Sachiyo
Matsushima, Tomoko
Hase, Kazuo
author_facet Oki, Eiji
Shinto, Eiji
Shimokawa, Mototsugu
Yamaguchi, Shigeki
Ishiguro, Megumi
Hasegawa, Seiji
Takii, Yasumasa
Ishida, Hideyuki
Kusumoto, Tetsuya
Morita, Masaru
Tomita, Naohiro
Shiozawa, Manabu
Tanaka, Masafumi
Ozawa, Heita
Hashiguchi, Yojiro
Ohnuma, Shinobu
Tada, Sachiyo
Matsushima, Tomoko
Hase, Kazuo
author_sort Oki, Eiji
collection PubMed
description 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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09088-6.
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spelling pubmed-86726292021-12-17 Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients Oki, Eiji Shinto, Eiji Shimokawa, Mototsugu Yamaguchi, Shigeki Ishiguro, Megumi Hasegawa, Seiji Takii, Yasumasa Ishida, Hideyuki Kusumoto, Tetsuya Morita, Masaru Tomita, Naohiro Shiozawa, Manabu Tanaka, Masafumi Ozawa, Heita Hashiguchi, Yojiro Ohnuma, Shinobu Tada, Sachiyo Matsushima, Tomoko Hase, Kazuo BMC Cancer Research 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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09088-6. BioMed Central 2021-12-14 /pmc/articles/PMC8672629/ /pubmed/34906120 http://dx.doi.org/10.1186/s12885-021-09088-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Oki, Eiji
Shinto, Eiji
Shimokawa, Mototsugu
Yamaguchi, Shigeki
Ishiguro, Megumi
Hasegawa, Seiji
Takii, Yasumasa
Ishida, Hideyuki
Kusumoto, Tetsuya
Morita, Masaru
Tomita, Naohiro
Shiozawa, Manabu
Tanaka, Masafumi
Ozawa, Heita
Hashiguchi, Yojiro
Ohnuma, Shinobu
Tada, Sachiyo
Matsushima, Tomoko
Hase, Kazuo
Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients
title Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients
title_full Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients
title_fullStr Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients
title_full_unstemmed Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients
title_short Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients
title_sort evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage iii colon cancer patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672629/
https://www.ncbi.nlm.nih.gov/pubmed/34906120
http://dx.doi.org/10.1186/s12885-021-09088-6
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