CD103阳性肿瘤浸润淋巴细胞与卵巢高级别浆液性癌患者预后关系的研究

程会贤; 陈名园; 陈婷婷; 张燕; 王梅; 刘天民; 况薇; 王巍

doi:10.12354/j.issn.1000-8179.2022.20220391

CD103阳性肿瘤浸润淋巴细胞与卵巢高级别浆液性癌患者预后关系的研究

Analysis of the relationship between CD103-positive tumor-infiltrating lymphocyte and prognosis of patients with high-grade serous ovarian cancer

摘要

摘要:
目的评估CD103阳性（CD103+）肿瘤浸润淋巴细胞（tumor-infiltrating lymphocyte，TIL）在实施初次肿瘤减灭术（debulking surgery，PDS）与新辅助化疗（neoadjuvant chemotherapy，NACT）的卵巢高级别浆液性癌（high-grade serous ovarian carcinoma，HGSC）患者中分布、表达差异与临床病理特征及预后的关系。
方法收集2018年6月至2019年6月四川大学华西第二医院收治的137例HGSC患者的临床病理资料，将患者石蜡组织标本制成组织芯片，分为 PDS组83例和NACT组54例。采用免疫组织化学法和免疫荧光共染法观察CD103+TIL与CD8阳性（CD8+）、CD4阳性（CD4+）TIL的关系，并采用相应的统计学方法分析CD103+ TIL与患者治疗、预后的关系。
结果采用χ²检验显示，NACT组CD103+TIL、CD8+TIL表达均高于PDS组（P=0.026、P=0.029），且CD103+TIL、CD8+TIL与化疗敏感性具有显著性相关（P=0.03、P=0.018），两组患者CD4+TIL与所有临床病理特征均无显著性相关（P>0.05）。Spearman相关性检验显示，CD103+TIL与CD8+TIL具有显著性相关（P<0.01）。免疫组织化学法和免疫荧光共染法结果显示，CD103+TIL实际多为CD8+TIL。单因素及Cox比例风险回归模型多因素生存分析发现，仅在肿瘤上皮内CD103+TIL、CD8+TIL的表达具有预后意义，是HGSC的独立预后因素（P<0.05）。
结论 HGSC患者CD103+TIL主要分布于肿瘤上皮内，是免疫活性更高的CD8+TIL亚群，因此CD103+TIL较CD8+TIL可更好地预测患者预后。

Abstract:
Objective We compared the expression and distribution differences of CD103-positive (CD103+) tumor-infiltrating lymphocyte (TIL) in a cohort of patients with high-grade serous ovarian carcinoma (HGSC) between those who were treated with primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT), followed by evaluating the relationship between CD103+TIL and clinical pathological characteristics and prognosis of the patient.
Methods A total of 137 patients with detailed clinical data were selected between June 2018 and June 2019 at West China Second University Hospital, Sichuan University. The paraffin specimens were used to make tissue microarrays, with 83 cases in the PDS group and 54 cases in the NACT group. The relationship between CD103+TIL and CD8-, CD4-positive (CD8+, CD4+) TIL, as well as the expression and distribution of CD103+TIL in tumor tissue of two patient groups were observed by immunohistochemistry and immunofluorescence co-staining analyses. Further, appropriate statistical methods were used to evaluate the correlation between CD103+TIL expression and clinical treatment and prognosis in patients.
Results χ² test results revealed that the expression of CD103+TIL and CD8+TIL in the NACT group was higher than that in the PDS group (P=0.026 and P=0.029). CD103+TIL and CD8+TIL were closely associated with chemotherapy sensitivity (P=0.030 and P=0.018); in the NACT cohort. However, there was no significance with CD4+TIL and all clinical pathological characteristics in the PDS and NACT cohort (P>0.05). Spearman test confirmed the strong correlation between the expression of CD103+TIL and CD8+TIL (P<0.01). Also, immunohistochemistry and immunofluorescence co-staining analyses directly confirmed that CD103+TIL were primarily CD8+TIL cells. The univariable and Cox proportional hazard model multivariable survival analysis supported that only CD103+TIL and CD8+TIL in tumor epithelial cells had prognostic significance (P<0.05).
Conclusions CD103+TIL in patients with ovarian HGSC is mainly distributed in the tumor epithelium and is a subset of CD8+TIL with higher activity. CD103+TIL is a better prognostic factor than CD8+TIL.

HTML全文

参考文献(14)

施引文献

资源附件(0)