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

Translational Lung Cancer Research
Myung Jin SongYoon Soo Chang

Abstract

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. 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. 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 <0.015). Male LUSC tumors had a higher probability of having more subclones than female tumors (2.28 vs. 1.89, P-value =0.002, Welch Two Sample t-test). On comparing the gene expression in the tumors that were comprised of five subclones with those of a single clone, 291 genes were found to be upregulated and 102 genes were found to be downregulated in the five subclone tumors. The upregulated genes included UGT1A10, SRY, FDCSP, MRLM, and ERE...Continue Reading

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