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Abstract Background The expression profiles and molecular mechanisms of CXC chemokine receptors (CXCRs) in Lung adenocarcinoma (LUAD) have been extensively explored. However, the comprehensive prognostic values of CXCR members in LUAD have not yet been clearly identified. Methods Multiple available datasets, including Oncomine datasets, the cancer genome atlas (TCGA), HPA platform, GeneMANIA platform, DAVID platform and the tumor immune estimation resource (TIMER) were used to detect the expression of CXCRs in LUAD, as well as elucidate the significance and value of novel CXCRs-associated genes and signaling pathways in LUAD. Results The mRNA and/or protein expression of CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CXCR6 displayed predominantly decreased in LUAD tissues as compared to normal tissues. On the contrary, compared with the normal tissues, the expression of CXCR7 was significantly increased in LUAD tissues. Subsequently, we constructed a network including CXCR family members and their 20 related genes, and the related GO functions assay showed that CXCRs connected with these genes participated in the process of LUAD through several signal pathways including Chemokine signaling pathway, Cytokine-cytokine receptor interaction and Neuroactive ligand-receptor interaction. TCGA and Timer platform revealed that the mRNA expression of CXCR family members was significantly related to individual cancer stages, cancer subtypes, patient’s gender and the immune infiltration level. Finally, survival analysis showed that low mRNA expression levels of CXCR2 (HR = 0.661, and Log-rank P = 1.90e−02), CXCR3 (HR = 0.674, and Log-rank P = 1.00e−02), CXCR4 (HR = 0.65, and Log-rank P = 5.01e−03), CXCR5 (HR = 0.608, and Log-rank P = 4.80e−03) and CXCR6 (HR = 0.622, and Log-rank P = 1.85e−03) were significantly associated with shorter overall survival (OS), whereas high CXCR7 mRNA expression (HR = 1.604, and Log-rank P = 4.27e−03) was extremely related with shorter OS in patients. Conclusion Our findings from public databases provided a unique insight into expression characteristics and prognostic values of CXCR members in LUAD, which would be benefit for the understanding of pathogenesis, diagnosis, prognosis prediction and targeted treatment in LUAD.

Objective: To analyze the expression of protein kinase C delta (PKCẟ, PRKCD) in Liver hepatocellular carcinoma and its clinical significance based on bioinformatics, in order to provide a new direction for the study of therapeutic targets for Liver hepatocellular carcinoma. Methods: The PRKCD gene expression data and patient clinical information data in Liver hepatocellular carcinoma tissues and adjacent tissues were downloaded from The TCGA (The Cancer Genome Atlas) and UCSC Xena databases. The mRNA expression of PRKCD in Liver hepatocellular carcinoma was analyzed, and the protein expression of PRKCD in Liver hepatocellular carcinoma was analyzed by Human Protein Atlas (HPA) databases. Furthermore, its relationship with clinicopathological features and prognosis in patients with Liver hepatocellular carcinoma was analyzed. GSEA enrichment analysis were carried out for PRKCD in Liver hepatocellular carcinoma. Finally, the causes of changes in PRKCD expression were analyzed from the perspective of genetic and epigenetics based on collated liver hepatocellular carcinoma data. Results: Both the mRNA and protein expression level of PRKCD gene in Liver hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Its expression level was correlated with TNM stage, Histologic grade,Alpha fetoprotein (AFP) and Living status in clinicopathological features, and its expression level has certain clinical diagnostic accuracy. Kaplan-Meier analysis showed that the prognosis of patients with low PRKCD expression was significantly better than that with high PRKCD expression. Univariate and multivariate Cox regression analysis showed that PRKCD was an independent prognostic factor in patients with Liver hepatocellular carcinoma, and it was also found that the risk ratio of TNM stage III and stage IV survival curve (HR) was significantly greater than that of stage I and stage II. GSEA analysis showed that it was enriched in cell cycles and DNA replication, and was positively correlated with PRKCD. Enrichment analysis found that PRKCD is mainly involved in the chemokine signaling pathway, NOD-like receptor signaling pathway, PPAR signaling pathway, adipocytokine signaling pathway and T-cell receptor signaling pathway. Finally, through genetic and epigenetic analysis, it is found that the increase in the number of copies of genes will increase the expression level of PRKCD, and the methylation level is negatively correlated with the expression level of PRKCD. Conclusion: PRKCD gene is upregulated in Liver hepatocellular carcinoma tissues, and its overexpression level is closely related to patient poor prognosis. [ABSTRACT FROM AUTHOR]