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评估程序性死亡配体 1 mRNA 表达和免疫阳性及其与印度肺癌患者生存结局的相关性。

Evaluation of the programmed death-ligand 1 mRNA expression and immunopositivity and their correlation with survival outcomes in Indian lung cancer patients.

机构信息

Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.

出版信息

Hum Cell. 2022 Jan;35(1):286-298. doi: 10.1007/s13577-021-00647-4. Epub 2021 Nov 17.

Abstract

The presence of membranous immunopositivity of programmed death-ligand 1 (PD-L1) in tumors serves as a key determinant of response to immune checkpoint inhibitors. However, there are very limited studies on the evaluation of the PD-L1 mRNA expression and immunopositivity and their correlation with therapeutic response and survival outcomes, especially in Indian lung cancer patients. In this prospective study, conducted between 2017 and 2020, we collected biopsies and surgically resected tumors from 173 lung cancer patients. PD-L1 immunopositivity and mRNA expression were determined by immunohistochemistry using SP263 assay and qRT-PCR, respectively. PD-L1 expression was correlated with various clinicopathological variables, response to therapy, and survival outcomes using appropriate statistical methods. The median age was 60 years (range 33-81 years) with the majority of patients being male (86.5%) and smokers (83%). Histologically, the majority of patients were non-small cell lung cancer (89.4%) and of squamous cell carcinoma histology (64.3%). PD-L1 immunopositivity in tumor cells (tumor proportion score (TPS) ≥ 1%) was detected in 37.6%, while high immunopositivity (TPS ≥ 50%) was detected in 16.8% of lung cancer patients. Almost 76% of lung cancer patients with PD-L1 TPS ≥ 50% belonged to PD-L1 mRNA high-expression group. PD-L1 mRNA expression and immunopositivity did not correlate with response to therapy and survival outcomes. We conclude that PD-L1 immunopositivity and mRNA expression do not seem to serve as a prognostic biomarker for lung cancer patients treated with chemotherapy. More prospective studies should be planned to evaluate the predictive and prognostic relevance of PD-L1 expression in Indian lung cancer patients being treated with immune checkpoint inhibitors.

摘要

肿瘤中程序性死亡配体 1(PD-L1)的膜免疫阳性存在是对免疫检查点抑制剂反应的关键决定因素。然而,关于 PD-L1 mRNA 表达和免疫阳性及其与治疗反应和生存结果的相关性的评估,特别是在印度肺癌患者中,研究非常有限。在这项于 2017 年至 2020 年期间进行的前瞻性研究中,我们从 173 名肺癌患者中收集了活检和手术切除的肿瘤。使用 SP263 检测法通过免疫组织化学法测定 PD-L1 免疫阳性和 mRNA 表达,并用 qRT-PCR 分别进行测定。使用适当的统计方法,将 PD-L1 表达与各种临床病理变量、治疗反应和生存结果相关联。中位年龄为 60 岁(范围 33-81 岁),大多数患者为男性(86.5%)和吸烟者(83%)。组织学上,大多数患者为非小细胞肺癌(89.4%)和鳞状细胞癌组织学(64.3%)。在 37.6%的肺癌患者中检测到肿瘤细胞 PD-L1 免疫阳性(肿瘤比例评分(TPS)≥1%),而在 16.8%的肺癌患者中检测到高免疫阳性(TPS≥50%)。在 PD-L1 TPS≥50%的肺癌患者中,近 76%属于 PD-L1 mRNA 高表达组。PD-L1 mRNA 表达和免疫阳性与治疗反应和生存结果无关。我们得出结论,PD-L1 免疫阳性和 mRNA 表达似乎不能作为接受化疗的肺癌患者的预后生物标志物。应计划进行更多的前瞻性研究,以评估 PD-L1 表达在接受免疫检查点抑制剂治疗的印度肺癌患者中的预测和预后相关性。

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