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.

Investigating the evolution process of lung adenocarcinoma via random walk and dynamic network analysis

“…Furthermore, the yellowish pink background represents the modules that we show in detail, and the number represents the sequence of the functions. The result obtained prove that the biological functions associated with the B cell and CXCR family play significant roles in LUAD ( Gangadhar et al, 2010 ; Wang et al, 2019 ; Liao et al, 2021 ; Hu et al, 2022 ). Therefore, among the core biological functions we obtained, the biological functions of B-cell differentiation, B-cell activation, B-cell receptor signaling pathway, and CXCR chemokine receptor binding are associated with LUAD.…”

Identification Of Endothelial Cell Immune-related Gene Signature for Lung Adenocarcinoma by Integrated Analysis of Single-cell and Bulk RNA Sequencing Data

“…All of these genes are related to survival in patients with lung adenocarcinoma. CXC chemokine receptors play a significant role in immune surveillance, inflammation, tissue fostering and maintenance 19 . A remarkable increase in the survival rate of patients with lung adenocarcinoma was observed due to a notable increase in CXCR4 expression 19 .…”

“…CXC chemokine receptors play a significant role in immune surveillance, inflammation, tissue fostering and maintenance 19 . A remarkable increase in the survival rate of patients with lung adenocarcinoma was observed due to a notable increase in CXCR4 expression 19 . In the protein interaction network, PTPRC was most likely the core gene of the network.…”

Circ_0026579 knockdown ameliorates lipopolysaccharide‐induced human lung fibroblast cell injury by regulating CXCR1 via miR‐370‐3p

“…Recent studies confirmed that pneumonia occurrence involved the regulation of miRNAs 13,14 . Chemokines are small molecules that can affect cancer cell proliferation and metastasis and participate in cellular secretion and structure 15 . Among them, CXC chemokines are localised on the cell membrane and are commonly expressed on the neutrophil surface.…”

“…13,14 Chemokines are small molecules that can affect cancer cell proliferation and metastasis and participate in cellular secretion and structure. 15 Among them, CXC chemokines are localised on the cell membrane and are commonly expressed on the neutrophil surface. The chemokine receptor CXCR1 is also expressed in lung structural cells, including fibroblasts.…”