Small-cell lung cancer (SCLC) is a type of lung cancer with early metastasis, and high recurrence and mortality rates. The molecular mechanism is still unclear and further research is required. The aim of the present study was to examine the pathogenesis and potential molecular markers of SCLC by comparing the differential expression of mRNA and microRNA (miRNA) between SCLC tissue and normal lung tissue. A transcriptome sequencing dataset (GSE6044) and a non-coding RNA sequence dataset (GSE19945) were downloaded from the Gene Expression Omnibus (GEO) database. In total, 451 differentially expressed genes (DEGs) and 134 differentially expressed miRNAs (DEMs) were identified using the R limma software package and the GEO2R tool of the GEO, respectively. The Gene Ontology function was significantly enriched for 28 terms, and the Kyoto Encyclopedia of Genes and Genomes database had 19 enrichment pathways, mainly related to ‘cell cycle’, ‘DNA replication’ and ‘oocyte meiosis mismatch repair’. The protein-protein interaction network was constructed using Cytoscape software to identify the molecular mechanisms of key signaling pathways and cellular activities in SCLC. The 1,402 miRNA-gene pairs encompassed 602 target genes of the DEMs using miRNAWalk, which is a bioinformatics platform that predicts DEM target genes and miRNA-gene pairs. There were 19 overlapping genes regulated by 32 miRNAs between target genes of the DEMs and DEGs. Bioinformatics analysis may help to better understand the role of DEGs, DEMs and miRNA-gene pairs in cell proliferation and signal transduction. The related hub genes may be used as biomarkers for the diagnosis and prognosis of SCLC, and as potential drug targets.
Cinobufotalin injection is a water-soluble preparation extracted from the skin secretion of Bufo bufo gargarizans Cantor or B. melanotictus Schneider, which has been widely used as an adjuvant treatment in lung cancer patients. This study aimed to evaluate the clinical efficacy and safety of cinobufotalin (PubChem CID: 259776) injection as an adjunctive treatment for lung cancer. We designed a meta-analysis that performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We aim to include randomized controlled trials by systematically searching the PubMed, EMBASE, CNKI, Wanfang database, VIP, CBM, the Cochrane Central Register of Controlled Trials, and Chinese Clinical Trial Registry from inception to Mar 1, 2020, comparing the difference between the use of cinobufotalin injection as an adjunctive treatment and a control group without cinobufotalin injection. The objective response rate (ORR) and quality of life (QOL) will be defined as the primary outcomes, and the disease control rate (DCR) and adverse events will be defined as the secondary outcomes. We included 21 articles with 1735 cases of lung cancer patients. Comparison results show that combining with cinobufotalin injection can improve ORR (OR = 1.77, 95% CI [1.43, 2.21], P < 0.001), with low heterogeneity ( P = 0.94, I2 = 0%); DCR (OR = 2.20, 95% CI [1.70, 2.85], P < 0.001), with low heterogeneity ( P = 0.60, I2 = 0%); KPS score (OR = 3.10, 95% CI [2.23, 4.32], P < 0.001), with low heterogeneity ( P = 0.85, I2 = 0%); and the effect of pain relief (OR = 2.68, 95% CI [1.30, 5.55], P = 0.008), with low heterogeneity ( P = 0.72, I2 = 0%). Low-to-moderate evidence shows that cinobufotalin injection combined with chemotherapy can significantly increase ORR, DCR, QOL, and the effect of pain relief. Meanwhile, cinobufotalin injection did not bring additional adverse events such as hematological toxicity, gastrointestinal toxicity, cardiotoxicity, hepatotoxicity, and nephrotoxicity; however, multicenter, large-sample, high-quality clinical research results are still needed to reveal the therapeutic effect of cinobufotalin injection in small-cell lung cancer (PROSPERO registration number: CRD42020170052).
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