[关键词]
[摘要]
目的:研究2型固有淋巴样细胞(ILC2)和髓源性抑制细胞(MDSC)及其相关细胞因子IL-13和诱导型一氧化氮合酶 (iNOS)在宫颈癌(CC)中的表达,并基于其构建CC发病风险的列线图预测模型。方法:采集2022年5月至2024年1月在新疆医 科大学第一附属医院手术切除的40例CC组织及100例外周血作为CC组,选取同期收治的30例子宫肌瘤经CC筛查为阴性的宫 颈组织和100例正常健康个体外周血作为对照组。用多重免疫荧光技术(mIF)及免疫组化染色(IHC)法检测两组组织中ILC2和 MDSC细胞浸润及其相关细胞因IL-13和iNOS的表达;使用流式细胞术和ELISA技术分别检测两组外周血中ILC2和MDSC及 IL-13和iNOS的表达差异;通过Person相关性分析评估其相关性;使用单因素和多因素Logistic分析来确定ILC2和MDSC及IL-13 和iNOS是否为CC发病的独立危险因素,再利用R软件建立免疫预测模型,使用ROC曲线下面积(AUC值)、Hosmer-Lemeshow 检验、校准曲线、临床决策曲线和临床影响曲线来分别评估模型。结果:CC组中ILC2及MDSC及其相关细胞因子IL-13和iNOS 均高于对照组(均P < 0.05),且其均呈正相关(均P < 0.05);经过单因素及多因素Logistic回归分析显示,ILC2、MDSC及IL-13、 iNOS均是CC发病的独立危险因素(均P < 0.05);基于这些危险因素的CC发病列线图,经过验证提示,该列线图模型具有一定的 临床实用价值。结论:ILC2和MDSC及其相关的细胞因子IL-13和iNOS在CC组织及外周血中均呈高表达,基于这些危险因素 构建的预测模型具有良好的预测能力和一定的实用性,为CC的早期诊断和治疗提供了一种简便有效的辅助工具。
[Key word]
[Abstract]
Objective: To investigate the expression of group 2 innate lymphoid cells (ILC2s) and myeloid-derived suppressor cells (MDSCs), along with their associated cytokines IL-13 and inducible nitric oxide synthase (iNOS), in cervical cancer (CC), and to construct a nomogram prediction model for assessing the risk of CC based on these factors. Methods: Samples were collected from May 2022 to January 2024 at the First Affiliated Hospital of Xinjiang Medical University, including 40 cases of CC tissue and 100 cases of peripheral blood as the CC group. Concurrently, cervical tissues from 30 cases of uterine fibroids screened negative for CC and peripheral blood from 100 healthy individuals were selected as the control group. Multiple immunofluorescence technology (mIF) and immunohistochemical staining (IHC) were utilized to detect the infiltration of ILC2s and MDSCs in tissue samples from both groups, along with the expression levels of related cytokines IL-13 and iNOS. Flow cytometry (FCM) and ELISA were employed to assess the differences in ILC2s, MDSCs, IL-13, and iNOS expression in peripheral blood samples. Pearson correlation was used to assess their correlations. Univariate and multivariate logistic analyses were performed to determine whether ILC2s, MDSCs, IL-13, and iNOS are independent risk factors for CC. An immune prediction model was established using R software, and the model was evaluated using the area under the ROC curve (AUC value), Hosmer-Lemeshow test, calibration curve, clinical decision curve, and clinical impact curve.Results: The levels of ILC2, MDSC, IL-13 and iNOS were all significantly higher in the CC group compared to the control group (all P < 0.05). Furthermore, they were positively correlated (all P < 0.05). Univariate and multivariate logistic regression analyses indicated that ILC2, MDSC, IL-13, and iNOS are independent risk factors for the development of CC (all P < 0.05). Subsequently, a nomogram based on these risk factors was developed and verified to have practical clinical value. Conclusion: ILC2, MDSC, and their associated cytokines IL-13 and iNOS are highly expressed in CC tissues and peripheral blood. The prediction model incorporating these risk factors has predictive capabilities and clinical utility, providing a valuable and accessible tool for early diagnosis and treatment of cervical cancer.
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[基金项目]
国家自然科学基金(No.82160545);省部共建中亚高发病成因与防治国家重点实验室基金(No.SKL-HIDCA-2022-5)