Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironment

Abstract

Pancreatic adenocarcinoma (PAAD), one of the most aggressive and lethal malignant tumors, is correlated with increased morbidity and mortality. CC chemokines can modulate the infiltration of immune cells and affect the clinical outcome of cancer patients. However, the therapeutic potential and prognostic value of CC chemokines in PAAD have not yet been elucidated. To do this, we comprehensively explore and analyze large amounts of data base on ONCOMINE, UALCAN, GEPIA2, LinkedOmics, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, DAVID 6.8, TRRUST, TIMER, TISIDB, DGIdb, and TTD. We found the transcriptional levels of CCL5/7/13/15/18/19/20 in PAAD tissues were remarkably increased, whereas the transcriptional level of CCL17 was decreased. CCL20 expression had significantly been correlated with the tumor stage of PAAD patients. High expressions of CCL5, CCL7, CCL13, CCL18, and CCL20 were notably correlated with the prognosis of patients. Moreover, patients with CCL18 and CCL19 alterations showed a poor prognosis in both overall survival (OS) and disease-specific survival (DSS). Patients with CCL5 and CCL15 alterations also presented a poor prognosis in OS. The key transcription factors for CC chemokines are RELA and NF-κB1. The functions of the differentially expressed CC chemokines were mainly correlated the chemokine signaling pathway, cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and so forth. We also discovered significant associations between the expression levels of CC chemokines and six infiltrating immune cells including, CD8⁺ T cells, CD4⁺ T cells, B cells, macrophages, neutrophils, and dendritic cells. The drug-gene interactions and related miRNAs of aberrant expression CC chemokines were also explored. Our study indicated the correlation between CC chemokines and PAAD and clarified the value of differentially expressed CC chemokines as potential therapeutic targets and prognostic markers for PAAD.