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Background Lung adenocarcinoma (LUAD) is the main pathological type of pulmonary malignant tumors. Synaptojanin 2 (SYNJ2), a member of the synaptojanin family, is considered as an attractive underlying therapeutic target in several types of cancer. The purpose of the current research was to comprehensively investigate the molecular function and underlying mechanism of SYNJ2 in LUAD with the goal of providing a promising therapeutic target for LUAD. Methods We applied tissue microarrays, immunohistochemistry (IHC), high-throughput RNA sequencing (RNA-seq) data, and gene microarrays of public databases to comprehensively examine the protein level, mRNA expression, clinical significance, and prognosis value of SYNJ2 in LUAD. The standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were computed to evaluate the comprehensive expression value of SYNJ2 in LUAD. Kaplan-Meier survival curves were plotted to determine the overall survival of SYNJ2 with different expression levels in LUAD. Univariate and multivariate cox regression analyses were implemented to investigate the dependent prognostic ability of SYNJ2 expression and the clinically-relevant traits of LUAD. Moreover, SYNJ2 co-expressed genes were screened for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) function analysis and protein–protein interactions (PPI) network construction. Results SYNJ2 overexpression in LUAD was confirmed by 2,299 LUAD samples and 1,387 non-tumor tissues obtained from tissue microarrays along with TCGA and public gene microarrays. The pooled SMD was 1.29 (95% CI: 1.09-1.48, I-square=78.6%, P |