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A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer
Author(s) -
Sho Shonan,
Court Colin M.,
Winograd Paul,
Russell Marcia M.,
Tomlinson James S.
Publication year - 2017
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.24781
Subject(s) - medicine , oncology , colorectal cancer , hazard ratio , proportional hazards model , cancer , concordance , stage (stratigraphy) , multivariate analysis , cohort , confidence interval , biology , paleontology
Background and Objectives Approximately 20‐40% of stage II/III colorectal cancer (CRC) patients develop relapse. Clinicopathological factors alone are limited in detecting these patients, resulting in potential under/over‐treatment. We sought to identify a prognostic tumor mutational profile that could predict CRC recurrence. Methods Whole‐exome sequencing data were obtained for 207 patients with stage II/III CRC from The Cancer Genome Atlas. Mutational landscape in relapse‐free versus relapsed cohort was compared using Fisher's exact test, followed by multivariate Cox regression to identify genes associated with cancer recurrence. Bootstrap‐validation was used to examine internal/external validity. Results We identified five prognostic genes ( APAF1 , DIAPH2 , NTNG1 , USP7 , and VAV2 ), which were combined to form a prognostic mutation panel. Patients with ≥1 mutation(s) within this five‐gene panel had worse prognosis (3‐yr relapse‐free survival [RFS]: 53.0%), compared to patients with no mutation (3‐yr RFS: 84.3%). In multivariate analysis, the five‐gene panel remained prognostic for cancer recurrence independent of stage and high‐risk features (hazard ratio 3.63, 95%CI [1.93‐6.83], P < 0.0001). Furthermore, its prognostic accuracy was superior to the American Joint Commission on Cancer classification (concordance‐index: 0.70 vs 0.54). Conclusions Our proposed mutation panel identifies CRC patients at high‐risk for recurrence, which may help guide adjuvant therapy and post‐operative surveillance protocols.