RNA sequencing identifies novel markers of non-small cell lung cancer

Abstract

IntroductionThe development of reliable gene expression profiling technology increasingly impacts our understanding of lung cancer biology. Here, we used RNA sequencing (RNA-Seq) to compare the transcriptomes of non-small cell lung cancer (NSCLC) and normal lung tissues and to investigate expression in lung cancer tissues. MethodsWe enrolled 88 male patients (mean age, 61.2 years) with NSCLC. RNA-Seq was performed on 88 pairs of NSCLC tumor tissue and non-tumor tissue from 54 patients with adenocarcinoma and 34 patients with squamous cell carcinoma. Immunohistochemistry was performed to validate differential candidate gene expression in a different NSCLC group. ResultsRNA-Seq produced 25.41×106 (±8.90×106) reads in NSCLC tissues and 24.70×106 (±4.70×106) reads in normal lung tissues [mean (±standard deviation)]. Among the genes expressed in both tissues, 335 were upregulated and 728 were downregulated ≥2-fold (p<0.001). Four upregulated genes – CBX3, GJB2, CRABP2, and DSP – not previously reported in lung cancer were studied further. Their altered expression was verified by immunohistochemistry in a different set of NSCLC tissues (n=154). CBX3 was positive in 90.3% (139 cases) of the samples; GJB2, in 22.7% (35 cases); CRABP2, in 72.1% (111 cases); and DSP, in 17.5% (27 cases). The positive rate of CRABP2 was higher in adenocarcinoma than squamous cell carcinoma (p<0.01). ConclusionsCBX3 and CRABP2 expression was markedly increased in lung cancer tissues and especially CRABP2 may be promising candidate genes in lung adenocarcinoma.