Comprehensive analysis of a chemokine- and chemokine receptor family-based signature for patients with lung adenocarcinoma

The clinical significance and comprehensive features of chemokines and their receptors in lung adenocarcinoma (LUAD) have not been clarified. We aimed to characterize the expression profiles of chemokine and chemokine receptor family members and construct a chemokine- and chemokine receptor-based prognosis signature. A total of 1511 patients with LUAD from seven independent cohorts were included in the study. The training set collected from The Cancer Genome Atlas (TCGA) database containing 468 cases. The validation was performed on the basis of six different cohorts downloaded from Gene Expression Omnibus (GEO) database. A five-chemokine- and chemokine receptor-(CXCL2, CXCL13, CCL26, CCL20, CX3CR1) based prognosis signature was constructed with TCGA dataset using LASSO Cox regression and Cox proportional hazards regression analysis. A multivariate analysis verified that this signature was an independent prognostic factor. The predictive value of this signature was further verified by other six independent cohorts and multiple clinical subtypes. We performed immune cell infiltration analysis and biological pathway analysis which provided more insight into this signature-related immune and inflammatory landscape and clarified the intrinsic molecular mechanism by which this signature could be used to predict clinical prognosis. Furthermore, we explored the close relationship between this signature and tumor mutation burden (TMB), neoantigen burden, PD-1, PD-L1, CTLA4, TIDE score, T cell-inflamed score. This signature provided a robust prognostic biomarker for LUAD and could serve as a predictor for immunotherapy response, which may be used as an important supplement to immunotherapy to achieve individualized tumor treatment by optimizing the prognostic management and immunotherapy for patients with LUAD.

Automated summary

This study characterized the expression profiles of chemokine and chemokine receptor family members in LUAD, and constructed a prognosis signature based on five chemokines and chemokine receptors. The signature was verified to be an independent prognostic factor for LUAD and provided a robust prognostic biomarker, showing potential for predicting immunotherapy response.