Comprehensive analysis of CXCR family members in lung adenocarcinoma with prognostic values

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.

Keywords: CXC chemokine receptors (CXCRs); Lung adenocarcinoma (LUAD); Prognostic values.

Fig. 1

Transcriptional expressions of different CXCR family members in different types of cancers. The data were compared by the t-test and cut-off P-value and fold change were as following: P-value < 0.05, fold change = 1.5, gene rank = 10%. (Red indicates over-expression, blue indicates down-expression)

Fig. 2

MRNA expressions of CXCR family members in patients with LUAD and normal lung tissues. The mRNA expressions of different CXCR family members were significantly regulated in patients with LUAD from the TCGA database (*P < 0.05, **P < 0.01, ***P < 0.001.)

Fig. 3

Protein expressions of CXCR family members in patients with NSCLC and normal lung tissues. Compared to normal samples protein expressions of CXCR1, CXCR3 and CXCR5 were significantly down-regulated and the protein expressions of CXCR7 was up-regulated

Fig. 4

Function enrichment of CXCRs family members. A Network of CXCRs and their 20 related genes was analyzed. B Cellular component; C Biological processes; D Molecular functions; E KEGG pathway analysis

Fig. 5

Association of mRNA expression of CXCRs family members with cancer stages of LUAD patients. The mRNA expression of CXCRs family members in normal people or in LUAD patients in different stages (*P < 0.05; **P < 0.01; ***P < 0.001)

Fig. 6

Association of mRNA expression of CXCRs family members with gender of LUAD patients. The mRNA expression of CXCR family members in normal people or in LUAD patients in male or female (*P < 0.05; **P < 0.01; ***P < 0.001)

Fig. 7

Association of mRNA expression of CXCR family members with cancer subtype of LUAD patients. The mRNA expression of CXCR family members in normal people or in LUAD patients in different subtype (*P < 0.05; **P < 0.01; ***P < 0.001)

Fig. 8

Prognostic value of mRNA expression of CXCR family members in LUAD patients about OS. OS comparing the high and low expression of CXCRs family members in LUAD patients