Tumor-educated leukocytes mRNA as a diagnostic biomarker for non-small cell lung cancer

Abstract

Background: This study aimed to investigate the diagnostic and prognostic role of tumor-educated leukocytes (TELs) mRNA in Chinese patients with non-small cell lung cancer (NSCLC). Methods: The TELs collected underwent total RNA isolation. RNA-sequencing (RNA-seq) technology was used to analyze the transcriptome of the TELs. The mRNA expression levels of differential genes were analyzed by RT-qPCR. Statistical analyses were performed using Prism and SPSS by Mann–Whitney nonparametric test, Kruskal-Wallis test and one-way ANOVA. Results: We used RNA-seq technology to screen 95 differential genes (DEGs) from seven NSCLC and four controls, wherein 15 genes were upregulated, and 80 were downregulated. Of these, four genes were selected for further analysis, wherein one was upregulated (GPX1) and three were downregulated (BCL9L, MAP3K7CL, PCSK7). RT-qPCR was performed in 431 samples (237 NSCLC, 194 healthy donors). The four-gene panel showed significant differences (p < 0.001) in the expression levels between NSCLC and healthy samples. ROC curves of the panel revealed an AUC of 0.803, with a sensitivity of 73.8% and specificity of 75.3%. GPX1, BCL9L and PCSK7 genes distinguished early-stage NSCLC patients from healthy group (p < 0.05). When the three genes were combined to diagnose early-stage NSCLC, the diagnostic efficacy was 0.772, sensitivity was 73.7%, and specificity was 72.2%. In addition, the downregulated gene BCL9L was associated with chemotherapeutic effect. Conclusions: The present study provided a systematic description of gene expression profiling in the TELs. It is worth noting that these four genes may be potential candidate genes for NSCLC diagnostic biomarkers and provide a basis for further biological and functional studies.