Increased number of subclones in lung squamous cell carcinoma elicits overexpression of immune related genes

Background: Intratumoral heterogeneity is a cause of drug resistance that leads to treatment failure. We investigated the clinical implication of intratumoral heterogeneity inferred from the number of subclones that constituted a tumor and reasoned the etiology of subclonal expansion using RNA sequencing data. Methods: Simple nucleotide variation, clinical data, copy number variation, and RNA-sequencing data from 481 The Cancer Genome Atlas-Lung Squamous Cell Carcinoma (TCGA-LUSC) cases were obtained from the Genomic Data Commons data portal. Clonal status was estimated from the allele frequency of the mutated genes using the SciClone package. Results: The number of subclones that comprised a tumor had a positive correlation with the total mutations in a tumor (σ=0.477, P-value <0.001) and tumor stage (σ=0.111, P-value