PD1/PDL1 inhibitors have been adopted for the treatment of advanced non-small-cell lung cancer, and PDL1 expression has been investigated as a predictive biomarker for PD1/PDL1 inhibitor therapy. However, PDL1 lacks diagnostic accuracy in differentiating patients who are likely or unlikely to benefit. So, it is urgent and clinically significant to identify other associated predictive biomarkers for PD1/PDL1 inhibitor therapy. Our work was to identify PDL1-related biomarkers that could improve the patient selection for PD1/PDL1 inhibitor treatment. We obtained 500 genes coexpressed with PDL1 in lung adenocarcinoma from the TCGA database. Then, we identified 125 out of 500 genes differentially expressed in lung adenocarcinoma. A total of 39 genes were distinguished with prognostic value and associated with overall survival. Median survival time analysis based on gene expression level, protein-protein interaction analysis, GO and KEGG enrichment analyses, and significant GO and KEGG function consistency analyses were conducted to screen candidate biomarkers. Three candidate genes, BRCA1, BRIP1, and EREG, were identified to be functionally significantly coexpressed with PDL1. Functional enrichment analysis and protein-protein interaction networks further showed that these genes mainly participated in immune response and cell activation. Additionally, to find potential adjuvant therapeutic targets in PD1/PDL1 inhibitor treatment, we performed transcription factor prediction analysis. A group of negative differential expression but PDL1-related biomarkers has been identified, which might help to assess the clinical management of lung cancer patients. A combination of potential biomarkers and adjuvant therapeutic targets with PDL1 will predict the response to PD1/PDL1 inhibitors more accurately and help with the patient selection for more personalized immune checkpoint inhibitor treatment.

中文翻译：

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鉴定PDL1相关生物标志物以选择PD1 / PDL1抑制剂的肺腺癌患者。

PD1 / PDL1抑制剂已被用于治疗晚期非小细胞肺癌，PDL1的表达已被研究作为PD1 / PDL1抑制剂治疗的预测生物标志物。但是，PDL1在区分可能或不太可能受益的患者方面缺乏诊断准确性。因此，鉴定用于PD1 / PDL1抑制剂治疗的其他相关的预测性生物标志物是紧迫的并且在临床上具有重要意义。我们的工作是确定可以改善PD1 / PDL1抑制剂治疗的患者选择的PDL1相关生物标志物。我们从TCGA数据库中获得了在肺腺癌中与PDL1共表达的500个基因。然后，我们从肺腺癌中差异表达的500个基因中鉴定出125个。共有39个基因具有预后价值并与总生存期相关。基于基因表达水平，蛋白质-蛋白质相互作用分析，GO和KEGG富集分析以及显着的GO和KEGG功能一致性分析进行了中位生存时间分析，以筛选候选生物标记。已确定三个候选基因BRCA1，BRIP1和EREG与PDL1在功能上显着共表达。功能富集分析和蛋白质-蛋白质相互作用网络进一步表明，这些基因主要参与免疫应答和细胞活化。此外，为了找到PD1 / PDL1抑制剂治疗中潜在的辅助治疗靶标，我们进行了转录因子预测分析。已鉴定出一组负差异表达但与PDL1相关的生物标记，这可能有助于评估肺癌患者的临床治疗。