Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, People's Republic of China.
Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, Zhejiang, People's Republic of China.
J Cancer Res Clin Oncol. 2023 Jul;149(8):4195-4204. doi: 10.1007/s00432-022-04331-4. Epub 2022 Sep 2.
Chronic inflammation has been proven to be an important factor in carcinogenesis. Cytokines are the central mediators in the inflammatory microenvironment, and their release may be influenced by soluble HLA-G (sHLA-G). The aim of this study was to monitor the dynamic process of these soluble factors in patients with cervical cancer at Taizhou Hospital of Zhejiang Province, trying to understand their relationship with diagnosis, treatment, and prognosis.
We quantified plasma levels of sHLA-G and 12 cytokines using ELISA and flow cytometry, respectively, in the peripheral blood of patients with cervical cancer divided into three groups: preoperation, postoperation and clinical relapse. Healthy women were used as the control group. Data were analysed by non-parametric tests, receiver-operating characteristic (ROC) curves, and Kaplan-Meier plotter (log-rank test).
In this study, our findings showed that preoperation plasma levels of sHLA-G and the cytokines IL-6, IL-10, and IFN-γ in cervical cancer patients had a good discriminatory effect between cervical cancer patients and healthy women. It should be noted that plasma levels of sHLA-G, IL-6, and IL-10 were significantly decreased within 30 days after radical hysterectomy (P < 0.05). A positive correlation was observed between IL-6 and IL-10, IL-8 and IL-17 levels preoperatively. In contrast, sHLA-G levels were negatively correlated with IL-10 but not with other cytokines. An increased survival rate in patients with cervical cancer was associated with IL-5 < 1.70 pg/mL, IL-17 < 2.30 pg/mL, and IFN-α < 2.26 pg/mL preoperatively. In addition, our findings showed that the levels of cytokines IL-6, IL-8, IL-12p70, IL-17, and IFN-γ may be related to 5-year relapse rates and/or the metastasis of cervical cancer.
The current findings enhance our understanding of the dynamic process (preoperation, postoperation and clinical relapse) of sHLA-G and these cytokines in the plasma of patients with cervical cancer from diagnosis to prognosis. These biomarkers may play a potential therapeutic target role of such dynamic changes in the immunotherapy for cervical cancer.
慢性炎症已被证明是致癌的一个重要因素。细胞因子是炎症微环境中的中心介质，其释放可能受可溶性 HLA-G（sHLA-G）的影响。本研究的目的是监测浙江省台州医院宫颈癌患者这些可溶性因子的动态过程，试图了解它们与诊断、治疗和预后的关系。
我们使用酶联免疫吸附试验（ELISA）和流式细胞术分别定量检测了宫颈癌患者外周血中 sHLA-G 和 12 种细胞因子的水平，这些患者分为三组：术前、术后和临床复发。健康女性作为对照组。数据采用非参数检验、受试者工作特征（ROC）曲线和 Kaplan-Meier 绘图器（对数秩检验）进行分析。
在这项研究中，我们的研究结果表明，术前宫颈癌患者的 sHLA-G 水平和细胞因子 IL-6、IL-10 和 IFN-γ在宫颈癌患者和健康女性之间具有良好的鉴别效果。值得注意的是，根治性子宫切除术后 30 天内，sHLA-G、IL-6 和 IL-10 的血浆水平显著降低（P<0.05）。术前观察到 IL-6 和 IL-10、IL-8 和 IL-17 水平之间呈正相关。相反，sHLA-G 水平与 IL-10 呈负相关，但与其他细胞因子无关。宫颈癌患者的生存率增加与术前 IL-5<1.70pg/mL、IL-17<2.30pg/mL 和 IFN-α<2.26pg/mL 有关。此外，我们的研究结果表明，细胞因子 IL-6、IL-8、IL-12p70、IL-17 和 IFN-γ 的水平可能与宫颈癌的 5 年复发率和/或转移有关。
本研究结果增强了我们对从诊断到预后宫颈癌患者血浆中 sHLA-G 和这些细胞因子的动态过程（术前、术后和临床复发）的理解。这些生物标志物可能在宫颈癌免疫治疗中发挥潜在的治疗靶点作用，以应对这些动态变化。
