Tumor Epigenetic Signature and Survival in Resected Gastric Cancer Patients
- 1 April 2021
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American College of Surgeons
- Vol. 232 (4), 483-491e1
- https://doi.org/10.1016/j.jamcollsurg.2020.12.023
Abstract
Prognosis and management of surgical cancer patients. Specifically, microRNAs (miRs) hold promise as prognostic biomarkers because dysregulation of individual miRs is implicated in tumorigenesis, progression, and metastases of various malignancies, including gastric adenocarcinoma (GC). STUDY DESIGN: To identify miRs prognostic of survival after radical gastrectomy, we studied GC patients within The Cancer Genome Atlas (TCGA) who had undergone R0 or R1 resection and had data on clinical characteristics, overall survival (OS), and tumor miR expression. The miRs expressed by at least 15% of tumors were eligible for study. From 10 replicate samples, each with 80% of patients, miRs were selected using age-adjusted proportional hazards regression with stepwise selection. Cross-validated miRs (selected by multiple replicates) were retained if they optimized an accelerated failure-time model of OS using all patients. RESULTS: In this GC cohort (n 1/4 270), half (916/1,870) of miRs screened met our criteria for evaluation. Cross-validation identified 20 miRs as prognostic, of which 14 (miR-129-1, miR-373, miR-490, miR-597, miR-1185-2, miR-3943, miR-4756, miR-5683, miR-6510, miR-6733, miR-6808, miR-6855, miR-6882, miR-8072) were independently informative. The age-adjusted 14-miRNA panel remained significantly associated with OS after adjustment for pathologic prognostic factors (number of lymph nodes examined, number of positive lymph nodes) and other clinical covariates (TNM stage, residual tumor, tumor microsatellite instability, targeted molecular therapy, sex, race, ethnicity). Panel-predicted survival estimates below the upper tertile cut-off were associated with worse outcome (30% vs 74% OS at 3 years, p < 0.0001). CONCLUSIONS: In surgically resected GC patients, an epigenetic signature of miRs associated with survival has the potential to improve prognostication. (J Am Coll Surg 2021;232:483e492. ? 2021 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.)Keywords
Funding Information
- U.S. Department of Defense
This publication has 26 references indexed in Scilit:
- The long noncoding RNA colon cancer‐associated transcript‐1/miR‐490 axis regulates gastric cancer cell migration by targeting hnRNPA1IUBMB Life, 2016
- Large-scale profiling of microRNAs for The Cancer Genome AtlasNucleic Acids Research, 2015
- MicroRNAs: Promising chemoresistance biomarkers in gastric cancer with diagnostic and therapeutic potentialWorld Journal of Gastroenterology, 2014
- MicroRNA-373 is upregulated and targets TNFAIP1 in human gastric cancer, contributing to tumorigenesisOncology Letters, 2013
- Prognostic Value of the 7th AJCC/UICC TNM Classification of Noncardia Gastric CancerAnnals of Surgery, 2012
- The effectiveness of the new (7th) UICC N classification in the prognosis evaluation of gastric cancer patients: a comparative study between the 5th/6th and 7th UICC N classificationGastric Cancer, 2011
- 7th Edition of the AJCC Cancer Staging Manual: StomachAnnals of Surgical Oncology, 2010
- Evaluation of the Seventh American Joint Committee on Cancer/International Union Against Cancer Classification of gastric adenocarcinoma in comparison with the sixth classificationCancer, 2010
- Global Patterns of Cancer Incidence and Mortality Rates and TrendsCancer Epidemiology, Biomarkers & Prevention, 2010
- Survival prediction of gastric cancer by a seven-microRNA signatureGut, 2009