Prognostic Significance and Therapeutic Target of CXC Chemokines in the Microenvironment of Lung Adenocarcinoma

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most important subtypes of lung cancer and has a high morbidity and mortality. Inflammatory CXC chemokines in tumor microenvironment can stimulate tumor growth, invasion, and metastasis, affecting the prognosis of patients. However, the differential expression profiles, prognostic values, and specific mechanisms of the CXC chemokine family in LUAD have not been clarified. METHODS: Transcriptome expression profile data were extracted from TIMER and TCGA. GEPIA was used to compare the relationship between CXC chemokines and clinicopathologic parameters. The prognostic analysis was performed using a Kaplan–Meier curve in GEPIA. LinkedOmics and TRRUST were applied to conduct the enrichment analysis of the regulatory networks containing the kinase targets, miRNA targets, and transcriptional factor targets. The characteristics of immune infiltration and immune-related clinical outcomes were evaluated with TIMER algorithms. Single-cell RNA sequencing localization analysis of genes as prognostic biomarkers were performed by PanglaoDB. RESULTS: Nine differentially expressed genes were identified in LUAD compared to normal tissues. Aberrant expression of CXCL2 (P =0.0017), CXCL13 (P= 0.0271), CXCL16 (P= 0.016), and CXCL17 (P= 2.14e-5) was significantly correlated with clinical cancer stage. Furthermore, patients with low gene transcription of CXCL 7 (P = 0.017) and high expression of CXCL 17 (P = 0.00045) had a better prognosis in LUAD. We also found that immune cell infiltration was significantly correlated with LUAD microenvironment mediated by CXC chemokines. Cox proportional hazard model test was conducted and indicated that B cell infiltration could prolong the survival of the LUAD patients. CXCL17 exerted anti-tumors effect through pulmonary alveolar type II cells according to single-cell analysis. CONCLUSION: Our research identified the aberrant expression profiles and prognostic biomarkers of CXC chemokines in LUAD. This detailed analysis of the regulatory factor networks for CXC chemokine gene expression may provide novel insights for selecting potential immunotherapeutic targets.