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PD1和PDL1基因表达在肺癌中的预后意义:一项荟萃分析。

The Prognostic Significance of PD1 and PDL1 Gene Expression in Lung Cancer: A Meta-Analysis.

作者信息

Chang Chih-Hao, Shih Arthur Chun-Chieh, Chang Ya-Hsuan, Chen Hsuan-Yu, Chao Ying-Ting, Hsu Yi-Chiung

机构信息

Genome and Systems Biology Degree Program, Academia Sinica and National Taiwan University, Taipei, Taiwan.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

出版信息

Front Oncol. 2021 Nov 18;11:759497. doi: 10.3389/fonc.2021.759497. eCollection 2021.

Abstract

BACKGROUND

Immune checkpoint blockade therapy represents an extraordinary advance in lung cancer treatment. It is important to determine the expression of immune checkpoint genes, such as programmed cell death 1 (PD1) and programmed cell death-ligand 1 (PDL1), to develop immunotherapeutic strategies. The aim of this study was to explore the association between PD1 and PDL1 gene expression and prognoses and outcomes in lung cancer.

METHODS

This meta-analysis analyzed 1,251 patients from eight different microarray gene expression datasets and were evaluated for their prognostic implications and verified using another independent research.

RESULTS

The mean expression levels of PDL1 in adenocarcinoma (AD) and squamous cell carcinoma (SC) were significantly higher in patients who died than in patients who did not. There was a trend toward incremental increases in PD1 and PDL1 expression significantly decreasing the risk of relapse and death among AD patients (HR = 0.69; 95% CI = 0.53 ~ 0.91; HR = 0.68; 95% CI = 0.54 ~ 0.84, respectively) and SC patients (HR = 0.53; 95% CI = 0.32 ~ 0.89; HR = 0.78; 95% CI = 0.57 ~ 1.00 respectively), as early-stage patients in this study were more likely to have high expression of both PD1 and PDL1 than late-stage patients (P-trend < 0.05). In contrast, late-stage SC patients expressing one or more of the genes at a high level had a significantly elevated risk of relapse (HR = 1.51; 95% CI = 1.07 ~ 2.11) and death (HR = 1.41; 95% CI = 1.08 ~ 1.84). This result was consistent with the validation data set.

CONCLUSION

These findings indicate that high expression of PD1 and PDL1 is associated with superior outcome in early-stage lung cancer but an adverse outcome in late-stage lung cancer. The expression levels of PD1 and PDL1 individually or jointly are potential prognostic factors for predicting patient outcomes in lung cancer.

摘要

背景

免疫检查点阻断疗法是肺癌治疗领域的一项重大进展。确定免疫检查点基因的表达,如程序性细胞死亡蛋白1(PD1)和程序性细胞死亡配体1(PDL1),对于制定免疫治疗策略至关重要。本研究的目的是探讨PD1和PDL1基因表达与肺癌预后及结局之间的关联。

方法

这项荟萃分析对来自八个不同微阵列基因表达数据集的1251例患者进行了分析,并评估了其预后意义,并使用另一项独立研究进行了验证。

结果

腺癌(AD)和鳞状细胞癌(SC)患者中,死亡患者的PDL1平均表达水平显著高于未死亡患者。在AD患者(HR = 0.69;95% CI = 0.53 ~ 0.91;HR = 0.68;95% CI = 0.54 ~ 0.84)和SC患者(HR = 0.53;95% CI = 0.32 ~ 0.89;HR = 0.78;95% CI = 0.57 ~ 1.00)中,PD1和PDL1表达呈递增趋势,显著降低了复发和死亡风险,因为本研究中的早期患者比晚期患者更有可能同时高表达PD1和PDL1(P趋势<0.05)。相比之下,晚期SC患者高水平表达一种或多种基因的复发风险(HR = 1.51;95% CI = 1.07 ~ 2.11)和死亡风险(HR = 1.41;95% CI = 1.08 ~ 1.84)显著升高。这一结果与验证数据集一致。

结论

这些发现表明,PD1和PDL1的高表达与早期肺癌的良好结局相关,但与晚期肺癌的不良结局相关。PD1和PDL1的表达水平单独或联合是预测肺癌患者结局的潜在预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7be/8639141/1719cbaa55ab/fonc-11-759497-g001.jpg

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