A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer

Shonan Sho, Colin M. Court, Paul Winograd, Marcia M. Russell, James S. Tomlinson

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)996-1004
Number of pages9
JournalJournal of Surgical Oncology
Volume116
Issue number8
DOIs
StatePublished - Dec 15 2017
Externally publishedYes

Keywords

  • DNA mutational analysis
  • adjuvant chemotherapy
  • colonic neoplasms
  • colorectal surgery
  • neoplasm recurrence
  • surgical oncology

ASJC Scopus subject areas

  • Surgery
  • Oncology

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