晚期高级别浆液性卵巢癌患者血清sCD276水平与肿瘤免疫浸润及预后的关系-东南大学学报医学版

晚期高级别浆液性卵巢癌患者血清sCD276水平与肿瘤免疫浸润及预后的关系

单位：1. 琼海市人民医院妇科, 海南琼海 571400;
2. 海南省人民医院(海南医学院附属海南医院) 妇产科, 海南海口 570311;
3. 中南大学湘雅医学院附属海口医院妇产科, 海南海口 570208

分类号：R737.31

出版年·卷·期（页码）：2022·41·第四期（484-490）

摘要：

目的：探讨晚期高级别浆液性卵巢癌（HGSOC）患者血清可溶性CD276（sCD276）水平与肿瘤免疫浸润及预后的关系。方法：对2015年7月至2016年7月期间收集的87例晚期卵巢癌患者样本进行回顾性分析，包括51例晚期HGSOC和36例其他类型卵巢癌。另外选择同时期20例健康志愿者作为健康对照组。采用ELISA法检测血清sCD276和细胞因子水平。采用免疫组化法检测组织CD3、CD4、CD8、CD80、CD86、Foxp3和CD276阳性表达情况。随访时间至少5年。结果：与健康对照组相比，晚期卵巢癌患者血清sCD276水平显著升高（P<0.05）。对于晚期HGSOC患者，血清sCD276水平≥516 pg·ml^-1亚组患者无病生存时间和总生存时间短于血清sCD276水平<516 pg·ml^-1亚组（P<0.05）。COX回归分析显示，血清sCD276水平≥516 pg·ml^-1是晚期HGSOC患者复发风险和死亡风险增加的独立危险因素（P<0.05）。血清sCD276水平≥516 pg·ml^-1的晚期HGSOC患者淋巴结受累率更高（P=0.023）。此外，41例（80.39%）晚期HGSOC患者发现了CD276⁺表达，膜CD276⁺表达与血清sCD276水平升高、Foxp3⁺表达以及血清TNF-α、IFN-γ水平升高有关（P<0.05）。结论：晚期HGSOC患者血清sCD276水平升高与肿瘤组织浸润性Foxp3⁺ T细胞数量增加和预后不良有关，且肿瘤组织膜CD276⁺表达者血清TNF-α、IFN-γ水平普遍升高，血清sCD276水平可作为晚期HGSOC患者危险分层的简单无创生物标志物。

Objective: To investigate the correlation of serum soluble CD276(sCD276) level with tumor immune infiltration and prognosis in advanced high-grade serous ovarian cancer(HGSOC).Methods: A total of 87 patients with advanced ovarian cancer, including 51 patients with advanced HGSOC and 36 patients with other types of ovarian cancer were selected from July 2015 to July 2016 for the retrospective analysis. In addition, 20 healthy volunteers in the same period were collected as healthy controls. Serum sCD276 and cytokines were detected by ELISA. The expressions of CD3, CD4, CD8, CD80, CD86, Foxp3 and CD276 in tissues were evaluated by immunohistochemical staining. Follow-up was at least 5 years.Results: Compared with the healthy control group, the level of serum sCD276 in patients with advanced ovarian cancer was significantly higher(P<0.05). For patients with advanced HGSOC, patients in sCD276 level ≥ 516 pg·ml^-1 subgroups had shorter disease-free survival time and overall survival time than patients in sCD276 level<516 pg·ml^-1 subgroups(P<0.05). Furthermore, COX regression assay showed that serum sCD276 level ≥ 516 pg·ml^-1 was an independent risk factor for recurrence and mortality in advanced HGSOC patients(P<0.05). Advanced HGSOC patients with serum sCD276 level ≥ 516 pg·ml^-1 had a higher rate of lymph node involvement(P=0.023). Besides, 41 cases(80.39%) of advanced HGSOC patients had positive expression of membrane CD276(CD276⁺). The expression of membrane CD276⁺ was related to the increase of serum sCD276, Foxp3⁺, TNF-α and IFN-γ(P<0.05). Conclusion: The increase of serum sCD276 level in advanced HGSOC patients is associated with the increase of invasive Foxp3⁺ T cells and poor prognosis, and the serum TNF-α and IFN-γ levels are generally increased in patients with membrane CD276⁺in tumor tissue. The detection of serum sCD276 level can be used as a simple noninvasive biomarker for risk stratification in patients with advanced HGSOC.

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