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

 Myung Jin Song  ;  Sang Hoon Lee  ;  Eun Young Kim  ;  Yoon Soo Chang 
 TRANSLATIONAL LUNG CANCER RESEARCH, Vol.9(3) : 659-669, 2020-06 
Journal Title
Issue Date
Squamous lung carcinoma ; clonality ; intratumoral heterogeneity
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 <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 EREG, in order of magnitude of upregulation, and the biologic function of the upregulated genes was strongly enriched for the positive regulation of immune processes and inflammatory responses. Conclusions: Male LUSC tumors were composed of a greater number of subclones than female tumors. The tumors with large numbers of subclones had overexpressed genes that positively regulated the immune processes and inflammatory responses more than tumors that consisted of a single clone.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun Young(김은영) ORCID logo https://orcid.org/0000-0002-3281-5744
Song, Myung Jin(송명진) ORCID logo https://orcid.org/0000-0003-2218-8959
Lee, Sang Hoon(이상훈) ORCID logo https://orcid.org/0000-0002-7706-5318
Chang, Yoon Soo(장윤수) ORCID logo https://orcid.org/0000-0003-3340-4223
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