RNA sequencing analysis of small cell lung cancer reveals candidate chemotherapy insensitivity long noncoding RNAs and microRNAs

Ann Transl Med. 2020 Feb;8(4):121. doi: 10.21037/atm.2020.01.75.

Abstract

Background: The further progression of credible expression profiling analysis of genes continues to expand our understanding of the biological characteristics in lung cancer. In this study, RNA sequencing (RNA-Seq) was used to contrast the transcriptomics profiling of small cell lung cancer (SCLC) that acquired partial response (PR) and stable disease (SD)/progressive disease (PD) after first-line chemotherapy. We aimed to illuminate the underlying mechanisms of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) in the efficacy of SCLC first-line chemotherapy.

Methods: Six male patients (mean age, 64.2 years) with SCLC were enrolled in this study. RNA-Seq was executed on the tumor tissues from 3 patients with PR outcome and 3 patients with SD or PD therapeutic effect after first-line chemotherapy.

Results: RNA-Seq generated 26.67×106 (±8.7×106) reads in SCLC tissues [mean (±standard deviation)]. Analysis revealed that 64 lncRNAs had higher expression and 194 had lower expression in the PR group ≥2-fold (P<0.05). Three downregulated genes in the PR group [HOXA-AS3, cancer susceptibility 9 (CASC9), and KEGG] could have a role in the insensitivity of SCLC. A total of 1,303 differential miRNAs were defined between PR and the SD or PD SCLC group, while 520 miRNAs had higher expression, and 783 had lower expression in the PR group. Two lower expressed miRNAs in the PR group (miRNA 601 and miRNA 596) might be the key genes in SCLC chemotherapy insensitivity.

Conclusions: The expression of 3 gene (HOXA-AS3, CASC9, and KEGG) and 2 miRNAs (miRNA 601 and miRNA 596) were markedly decreased in SCLC patients who achieved PR. They thus might be the promising candidate genes in SCLC chemotherapy insensitivity.

Keywords: Small cell lung cancer (SCLC); chemotherapy insensitivity; long noncoding RNAs (lncRNAs); microRNAs (miRNAs).