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Prognosis of stage III colorectal carcinomas with FOLFOX adjuvant chemotherapy can be predicted by molecular subtype

Authors
 Yujin Kwon  ;  Minhee Park  ;  Mi Jang  ;  Seongju Yun  ;  Won Kyu Kim  ;  Sora Kim  ;  Soonmyung Paik  ;  Hyun Jung Lee  ;  Sungpil Hong  ;  Tae Il Kim  ;  Byungsoh Min  ;  Hoguen Kim 
Citation
 Oncotarget, Vol.8(24) : 39367-39381, 2017 
Journal Title
 Oncotarget 
Issue Date
2017
MeSH
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Biomarkers ; Tumor ; Chemotherapy ; Adjuvant ; Cluster Analysis ; Colorectal ; diagnosis ; Colorectal Neoplasms/drug therapy* ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/mortality* ; Computational Biology ; Female ; Fluorouracil/adverse effects ; Fluorouracil/therapeutic use ; Gene Expression Profiling ; Humans ; Leucovorin/adverse effects ; Leucovorin/therapeutic use ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds/adverse effects ; Organoplatinum Compounds/therapeutic use ; Prognosis ; Survival Analysis ; Transcriptome ; Treatment Outcome ; Substances ; Biomarkers ; Tumor ; Organoplatinum Compounds ; Leucovorin ; Fluorouracil ; Supplementary concept ; Folfox protocol
Keywords
DNA microarray ; colon cancer ; consensus molecular subtype ; mRNA expression-based molecular classification ; molecular subtype
Abstract
Individualizing adjuvant chemotherapy is important in patients with advanced colorectal cancers (CRCs), and the ability to identify molecular subtypes predictive of good prognosis for stage III CRCs after adjuvant chemotherapy could be highly beneficial. We performed microarray-based gene expression analysis on 101 fresh-frozen primary samples from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy and 35 matched non-neoplastic mucosal tissues. CRC samples were classified into four molecular subtypes using nonnegative matrix factorization, and for comparison, we also grouped CRC samples using the proposed consensus molecular subtypes (CMSs). Of the 101 cases, 80 were classified into a CMS group, which shows a 79% correlation between the CMS classification and our four molecular subtypes. We found that two of our subtypes showed significantly higher disease-free survival and overall survival than the others. Group 2, in particular, which showed no disease recurrence or death, was characterized by high microsatellite instability (MSI-H, 6/21), abundant mucin production (12/21), and right-sided location (12/21), this group strongly correlated with CMS1 (microsatellite instability immune type). We further identified the molecular characteristics of each group and selected 10 potential biomarker genes from each. When these were compared to the previously reported molecular classifier genes; we found that 31 out of 40 selected genes were matched with those previously reported. Our findings indicate that molecular classification can reveal specific molecular subtypes correlating with clinicopathologic features of CRCs and can have predictive value for the prognosis for stage III CRCs with FOLFOX adjuvant chemotherapy.
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DOI
10.18632/oncotarget.17023
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Kyu(김원규)
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Kim, Ho Keun(김호근)
Min, Byung Soh(민병소)
Park, Min Hee(박민희)
Paik, Soon Myung(백순명) ORCID logo https://orcid.org/0000-0001-9688-6480
Lee, Hyun Jung(이현정)
Hong, Sung Pil(홍성필)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160269
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