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

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.

Novel prognostic molecular markers in lung cancer (Review)

“…Moreover, the EMAF analysis, together with other factors, e.g. staging, grading, age, gender, and smoking, significantly improved the accuracy of predicting a 3-year survival (67).…”

Detection of the EGFR G719S Mutation in Non-small Cell Lung Cancer Using Droplet Digital PCR

“…The value of 20 located in the numerator of the equation corresponds to the final volume PCR mix, which was 20 µL. Mutant-allele fraction (MAF) data was also calculated as (16):…”

Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early‐stage NSCLC patients

“…DNA methylation has been recognized as cancer biomarkers and therapeutic targets for NSCLC [14][15][16][17][18][19][20][21], as well as other cancers [22,23], since it is stable to measure but is modifiable with proper interventions [24,25]. Also, aberrant DNA methylation of TRIM27 was identified affecting lung function in monozygotic twins [26].…”