Analysis of Chromosome 3P Genes Associated With Clinical Staging of Small Cell Lung Cancer and Prediction of Targeted Drugs

Abstract

BackgroundNowadays, the diagnosis of small-cell lung cancer (SCLC) remains a great challenge. Changes in the chromosome 3p (chr3) gene are usually observed in the pathogenesis of lung cancer, which seems to imply that these chr3 genes may be a diagnostic marker in the early stage of SCLC. MethodsBased on Differentially expressed genes (DEGs) screening analysis, Weighted gene co-expression network analysis, and Receiver operating characteristic (ROC) curves, this study explored the diagnostic value of the chr3 gene obtained from the University of California Santa Cruz Genome Browser Database in SCLC. Meanwhile, quantitative real-time Polymerase Chain Reaction (qRT-PCR) was used to reveal the expression patterns of diagnostic biomarkers in Human pulmonary alveolar epithelial cells and the SCLC cell line NCI-H146. The potential pathways involved in the diagnostic biomarkers were investigated by a single-gene Gene Set Enrichment Analysis (GSEA). Furthermore, drugs regulating the expression levels of diagnostic biomarkers were predicted by the Comparative Toxicogenomics Database (CTD).ResultsWe identified a total of 33 differentially expressed chr3 (DE-chr3) genes and 1156 hub genes associated with clinical features of SCLC, and functional enrichment analysis showed that all of these genes were significantly enriched in the cell cycle terms. Ultimately, the area under curve of the ROC curve demonstrated that the overlapping genes of the DE-chr3 genes and the hub genes, CDC25A, FYCO1, and RFTN1, were relatively accurate in distinguishing normal from SCLC samples, which were considered to be diagnostic biomarkers. CDC25A was overexpressed in SCLC samples, while FYCO1 and RFTN1 were highly expressed in normal samples, as evidenced by qRT-PCR results. Single-gene GSEA showed that diagnostic biomarkers were significantly associated with cell cycle, ABC transporter, immune cell differentiation, immune response, and multiple respiratory disease pathways. Further, a total of 141 drugs were predicted by the CTD to modulate the expression of diagnostic biomarkers, of which 8 drugs were the shared drugs for 3 diagnostic biomarkers.ConclusionsThis project provided 3 novel and powerful diagnostic biomarkers for SCLC based on the chr3 genes. Meanwhile, a guideline for the development and selection of drugs for clinical treatment based on diagnostic biomarkers was also included.