domingo, 4 de febrero de 2018

A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer. - PubMed - NCBI

A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer. - PubMed - NCBI



 2017 Dec;116(8):996-1004. doi: 10.1002/jso.24781. Epub 2017 Aug 2.

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

Sho S1,2Court CM1,2Winograd P1,2Russell MM1,2Tomlinson JS1,2,3.

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.

KEYWORDS:

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

PMID:
 
28767131
 
DOI:
 
10.1002/jso.24781

[Indexed for MEDLINE]

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