Exploration on the potential predictive value of regulator of G-protein signaling 2 in the efficacy of concurrent chemoradiotherapy on cervical squamous cell carcinoma

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Objective: Concurrent chemotherapy and radiotherapy (CCRT) has been applied as a therapeutic modality for cervical squamous cell carcinoma (CESC). Our aim is to investigate the potential marker(s) of the efficacy of CCRT in CESC. Material and Methods: Potential candidates predictive of the efficacy of CCRT in CESC were identified. Differentially expressed genes (DEGs) were screened, followed by performing functional enrichment analyses. CCRT-related biomarkers were identified. In addition, the CIBERSORT algorithm was employed to determine the immune cell infiltration. Immune cell subsets from donors and specific cytokines were evaluated, and the biological functions of CESC cells following cisplatin treatment or coculture with M2 macrophages were explored. Results: A total of 56 DEGs were singled out. These DEGs were enriched in pathways relevant to CESC and CCRT. They were narrowed down to eight CCRT-related biomarkers with good predictive values. Notably, most of the biomarkers were negatively correlated with M2 macrophages (P < 0.05), and regulator of G-protein signaling 2 (RGS2) exhibited low expression in CESC (P < 0.05). Flow cytometry results revealed that patients with CCRT-resistant CESC had high percentages of M2 macrophages, CD4 T cells, regulatory T cells and T helper 2 cells but low percentages of T helper 1 cells, and T helper 17 cells, M1 macrophages, and CD8 T cells (P < 0.05). Aside from interleukin (IL4) and IL-10, the remaining specific cytokines exhibited low expression in patients with CCRT-resistant CESC (P < 0.05). Furthermore, the cell cycle progression and metastasis of CESC cells were evidently promoted by M2 macrophages but were suppressed by cisplatin intervention (P < 0.05). Moreover, in CESC cells, cisplatin repressed the levels of IL-4 and IL-10 yet boosted those of the remaining cytokines, whereas M2 macrophages had the opposite effects (P < 0.05). RGS2 silencing promoted the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B/transcriptional signal transducer and activator 6 in macrophages, whereas RGS2 overexpression had the opposite effect (P < 0.05). Conclusion: This study interpreted and explored the possible predictive values of RGS2 in the efficacy of CCRT in CESC. It may provide other insights for the management of CESC.