Open Access

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
  • View Affiliations

  • 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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January 2018
Volume 15 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Shen, S., Wei, Y., Zhang, R., Du, M., Duan, W., Yang, S. ... Chen, F. (2018). Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival. Oncology Letters, 15, 795-802. https://doi.org/10.3892/ol.2017.7428
MLA
Shen, S., Wei, Y., Zhang, R., Du, M., Duan, W., Yang, S., Zhao, Y., Christiani, D. C., Chen, F."Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival". Oncology Letters 15.1 (2018): 795-802.
Chicago
Shen, S., Wei, Y., Zhang, R., Du, M., Duan, W., Yang, S., Zhao, Y., Christiani, D. C., Chen, F."Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival". Oncology Letters 15, no. 1 (2018): 795-802. https://doi.org/10.3892/ol.2017.7428