Abstract
The rising incidence and mortality rate of Uterine Corpus Endometrial Carcinoma (UCEC) pose significant health concerns. CC and CXC chemokines have been linked to tumorigenesis and cancer progression. Recognizing the growing significance of CC and CXC chemokines' diagnostic and prognostic significance in diverse cancer types, our objective was to comprehensively analyze the diagnostic and prognostic values of hub genes from the CC and CXC chemokines in UCEC, utilizing both in silico and clinical samples and cell lines-based approaches. In silico analyses include STRING, Cytoscape, Cytohubba, The Cancer Genome Atlas (TCGA) datasets analysis via the UALCAN, GEPIA, OncoDB, and MuTarget, SurvivalGenie, MEXPRESS, cBioPoratal, TIMER, ENCORI, and DrugBank. Meanwhile, clinical samples and cell lines based analyses include Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), targeted bisulfite sequencing (bisulfite-seq) analysis, and immunohistochemistry (IHC). Through present study, we identified CCL25 (CC motif chemokine ligand 25), CXCL10 (C-X-C motif chemokine ligand 10), CXCL12 (C-X-C motif chemokine ligand 12), and CXCL16 (C-X-C motif chemokine ligand 16) as crucial hub genes among the CC and CXC chemokines. Analyzing the expression data from TCGA, we observed a significant up-regulation of CCL25, CXCL10, and CXCL16 in UCEC samples compared to controls. In contrast, we noted a significant down-regulation of CXCL12 expression in UCEC samples. On clinical UCEC samples and cell lines analysis, the significant higher expression of CCL25, CXCL10, and CXCL16 and significant lower expression of CXCL12 were also denoted in UCEC samples than the controls via RT-qPCR and IHC analyses. Moreover, in silico analysis also confirmed the abnormal promoter methylation levels of the hub genes in TCGA UCEC samples, which was later validated by the clinical samples using targeted based bisulfite-seq analysis. In addition, various additional aspects of the CCL25, CXCL10, CXCL12, and CXCL16 have also been uncovered in UCEC during the present study. Our findings offer novel insights that contribute to the clinical utility of CCL25, CXCL10, CXCL12, and CXCL16 chemokines as potential diagnostic and prognostic biomarkers in UCEC.