Liu Yi, Xu Jie, Zou Xiaofeng, Li Li
Department of Gynecology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
School of Public Health, Zunyi Medical University, Zunyi, China.
Cytojournal. 2025 May 10;22:53. doi: 10.25259/Cytojournal_225_2024. eCollection 2025.
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.
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.
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 ( < 0.05), and regulator of G-protein signaling 2 (RGS2) exhibited low expression in CESC ( < 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 ( < 0.05). Aside from interleukin (IL4) and IL-10, the remaining specific cytokines exhibited low expression in patients with CCRT-resistant CESC ( < 0.05). Furthermore, the cell cycle progression and metastasis of CESC cells were evidently promoted by M2 macrophages but were suppressed by cisplatin intervention ( < 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 ( < 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 ( < 0.05).
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.
同步放化疗（CCRT）已被用作宫颈鳞状细胞癌（CESC）的一种治疗方式。我们的目的是研究CCRT治疗CESC疗效的潜在标志物。
确定预测CCRT治疗CESC疗效的潜在候选物。筛选差异表达基因（DEG），随后进行功能富集分析。鉴定CCRT相关生物标志物。此外，采用CIBERSORT算法确定免疫细胞浸润情况。评估供体的免疫细胞亚群和特定细胞因子，并探讨顺铂处理或与M2巨噬细胞共培养后CESC细胞的生物学功能。
共筛选出56个DEG。这些DEG富集于与CESC和CCRT相关的通路。它们被缩小到8个具有良好预测价值的CCRT相关生物标志物。值得注意的是，大多数生物标志物与M2巨噬细胞呈负相关（<0.05），并且G蛋白信号调节因子2（RGS2）在CESC中表达较低（<0.05）。流式细胞术结果显示，CCRT耐药的CESC患者中M2巨噬细胞、CD4 T细胞、调节性T细胞和辅助性T细胞2型的百分比高，但辅助性T细胞1型、辅助性T细胞17型、M1巨噬细胞和CD8 T细胞的百分比低（<0.05）。除白细胞介素（IL4）和IL-10外，其余特定细胞因子在CCRT耐药的CESC患者中表达较低（<0.05）。此外，M2巨噬细胞明显促进CESC细胞的细胞周期进程和转移，但顺铂干预可抑制（<0.05）。此外，在CESC细胞中，顺铂抑制IL-4和IL-10的水平，但提高其余细胞因子的水平，而M2巨噬细胞则有相反的作用（<0.05）。RGS2沉默促进巨噬细胞中磷脂酰肌醇3激酶/蛋白激酶B/转录信号转导子和激活子6的磷酸化，而RGS2过表达则有相反的效果（<0.05）。
本研究解释并探讨了RGS2在CCRT治疗CESC疗效中的可能预测价值。它可能为CESC的治疗提供其他见解。
