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Background Fragile histidine triad (FHIT) is a strong tumor suppressor gene, and cells deficient in FHITare prone to acquiring cancer-promoting mutations. Due to its location, deletions within FHITare common in cancer. Over 50% of cancers show loss of FHITexpression. However, to date, expression levels, gene regulatory networks, prognostic value, and target prediction of FHITin lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) have not been fully reported. Therefore, systematic analysis of FHITexpression, gene regulatory network, prognostic value, and targeted prediction in patients with LUAD and LUSC has important guiding significance, providing new therapeutic targets and strategies for clinical treatment of lung cancer to further improve the therapeutic effect of lung cancer.Methods Multiple free online databases were used for the abovementioned analysis in this study, including cBioPortal, TRRUST, Human Protein Atlas, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, and TIMER.Results FHITwas upregulated in patients with LUAD, and downregulated in patients with LUSC. Genetic alterations of FHITwere found in patients with LUAD (7%), and LUSC (10%). The promoter methylation of FHITwas lower in patients with LUAD and LUSC. FHITexpression significantly correlated with LUSC pathological stages. Furthermore, patients with LUAD and LUSC having low FHITexpression levels had a longer survival than those having high FHITexpression levels. FHITand its neighboring genes (the 50 most frequently altered neighboring genes of FHIT) functioned in the regulation of protein kinase and DNA binding in patients with LUAD, as well as cell channels and membrane potential in patients with LUSC. Gene ontology enrichment analysis revealed that the functions of FHITand its neighboring genes are mainly related to disordered domain-specific binding, protein kinase binding, and ion gated channel activity in patients with LUAD, as well as calcium ion binding and intracellular ligand-gated ion channel activity in patients with LUSC. Transcription factor targets of FHITand its neighboring genes in patients with lung cancer were found: USF1, SOX6, USF2, SIRT1, VHL, LEF1, EZH2, TP53, HDAC1, ESR1, EGR1, YY1, MYC, RELA, NFKB1, and E2F1 in LUAD; and HDAC1, DNMT1, and E2F1 in LUSC. We further explored the FHIT-associated kinase (PRKCQ, AURKB and ATM in LUAD as well as PLK3 in LUSC) and FHIT-associated miRNA targets (MIR-188, MIR-323, and MIR-518A-2 in LUAD). Furthermore, the following genes had the strongest correlation with FHITexpression in patients with lung cancer: NICN1, HEMK1,and BDH2in LUAD,and ZMAT1, TTC21A,and NICN1in LUSC. FHITexpression was positively associated with immune cell infiltration (B cell) in patients with LUAD, as well as B cell, CD8 + T, CD4 + T cells, macrophages, and dendritic cells in patients with LUSC. Nevertheless, FHITexpression was negatively associated with CD8 + T cells and neutrophils in patients with LUAD.Conclusions The expression, gene regulatory network, prognostic value and targeted prediction of FHITin patients with LUAD and LUSC were systematically analyzed and revealed in this study, thereby laying a foundation for further research on the role of FHITin LUAD and LUSC occurrence. This study provides new LUAD and LUSC therapeutic targets and prognostic biomarkers as a reference for fundamental and clinical research.

Background VEGFA is one of the most important regulators of angiogenesis and plays a crucial role in cancer angiogenesis and progression. Recent studies have highlighted a relationship between VEGFAexpression and renal cell carcinoma occurrence. However, the expression level, gene regulation network, prognostic value, and target prediction of VEGFAin renal cell carcinoma remain unclear. Therefore, system analysis of the expression, gene regulation network, prognostic value, and target prediction of VEGFAin patients with renal cell carcinoma is of great theoretical significance as there is a clinical demand for the discovery of new renal cell carcinoma treatment targets and strategies to further improve renal cell carcinoma treatment efficacy.Methods This study used multiple free online databases, including cBioPortal, TRRUST, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, Metascape, and TIMER for the abovementioned analysis.Results VEGFAwas upregulated in patients with kidney renal clear cell carcinoma (KIRC) and kidney chromophobe (KICH), and downregulated in patients with kidney renal papillary cell carcinoma (KIRP). Moreover, genetic alterations of VEGFAwere found in patients with renal cell carcinoma as follows: 4% (KIRC), 8% (KICH), and 4% (KIRP). The promoter methylation of VEGFAwas lower and higher in patients with clinical stages of KIRC and stage 1 KIRP, respectively. VEGFAexpression significantly correlated with KIRC and KIRP pathological stages. Furthermore, patients with KICH and KIRP having low VEGFAexpression levels had a longer survival than those having high VEGFAexpression levels. VEGFAand its neighboring genes functioned in the regulation of protein methylation and glycosylation, as well as muscle fiber growth and differentiation in patients with renal cell carcinoma. Gene Ontology enrichment analysis revealed that the functions of VEGFAand its neighboring genes in patients with renal cell carcinoma are mainly related to cell adhesion molecule binding, catalytic activity, acting on RNA, ATPase activity, actin filament binding, protease binding, transcription coactivator activity, cysteine-type peptidase activity, and calmodulin binding. Transcription factor targets of VEGFAand its neighboring genes in patients with renal cell carcinoma were found: HIF1A, TFAP2A, and ESR1 in KIRC; STAT3, NFKB1, and HIPK2 in KICH; and FOXO3, TFAP2A, and ETS1 in KIRP. We further explored the VEGFA-associated kinase (ATM in KICH as well as CDK1 and AURKB in KIRP) and VEGFA-associated microRNA (miRNA) targets (MIR-21 in KICH as well as MIR-213, MIR-383, and MIR-492 in KIRP). Furthermore, the following genes had the strongest correlation with VEGFAexpression in patients with renal cell carcinoma: NOTCH4, GPR4, and TRIB2in KIRC; CKMT2, RRAGD, and PPARGC1Ain KICH; and FLT1, C6orf223, and ESM1in KIRP. VEGFAexpression in patients with renal cell carcinoma was positively associated with immune cell infiltration, including CD8+T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells.Conclusions This study revealed VEGFAexpression and potential gene regulatory network in patients with renal cell carcinoma, thereby laying a foundation for further research on the role of VEGFAin renal cell carcinoma occurrence. Moreover, the study provides new renal cell carcinoma therapeutic targets and prognostic biomarkers as a reference for fundamental and clinical research.