Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival

Shen,Sipeng; Wei,Yongyue; Zhang,Ruyang; Du,Mulong; Duan,Weiwei; Yang,Sheng; Zhao,Yang; Christiani,David  C.; Chen,Feng

doi:10.3892/ol.2017.7428

Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival

Authors:
- Sipeng Shen
- Yongyue Wei
- Ruyang Zhang
- Mulong Du
- Weiwei Duan
- Sheng Yang
- Yang Zhao
- David C. Christiani
- Feng Chen
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Affiliations: Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211136, P.R. China, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA
Published online on: November 15, 2017 https://doi.org/10.3892/ol.2017.7428
Pages: 795-802
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Genetic intratumor heterogeneity is associated with tumor occurrence, development and overall outcome. The present study aims to explore the association between mutant‑allele fraction (MAF) heterogeneity and patient overall survival in lung cancer. Somatic mutation data of 939 non‑small cell lung cancer (NSCLC) cases were obtained from The Cancer Genome Atlas. Entropy‑based mutation allele fraction (EMAF) score was used to describe the uncertainty of individual somatic mutation patterns and to further analyze the association with patient overall survival. Results indicated that association between EMAF and overall survival was significant in the discovery set [hazard ratio (H)R=1.62; 95% confidence interval (CI): 1.08‑2.41; P=0.018] and replication set (HR=1.63; 95% CI: 1.11‑2.37; P=0.011). In addition, EMAF was also significantly different in lung adenocarcinoma and squamous cell carcinoma. Furthermore, a significant difference was indicated in early‑stage patients. Results from c‑index analysis indicated that EMAF improved the model predictive performance on the 3‑year survival beyond that of traditional clinical staging, particularly in early‑stage patients. In conclusion, EMAF successfully reflected MAF heterogeneity among patients with NSCLC. Additionally, EMAF improved the predictive performance in early‑stage patient prognosis beyond that of traditional clinical staging. In clinical application, EMAF appears to identify a subset of early‑stage patients with a poor prognosis and therefore may help inform clinical decisions regarding the application of chemotherapy after surgery.

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