Abstract

Lung cancer remains a leading cause of global cancer-related mortality, and the exploration of innovative therapeutic approaches, such as PD1/PDL1 immunotherapy, is critical. This study leverages comprehensive data from the Cancer Genome Atlas (TCGA) to investigate the differential expression of PD1/PDL1 in lung cancer patients and explores its implications. Clinical data, RNA expression, somatic mutations, and copy number variations of 1017 lung cancer patients were obtained from TCGA. Patients were categorized into high (HE) and low (LE) PD1/PDL1 expression groups based on mRNA levels. Analyses included differential gene expression, functional enrichment, protein-protein interaction networks, and mutational landscape exploration. The study identified 391 differentially expressed genes, with CD4 and PTPRC among the upregulated genes in the HE group. Although overall survival did not significantly differ between HE and LE groups, enrichment analysis revealed a strong association with immunoregulatory signaling pathways, emphasizing the relevance of PD1/PDL1 in immune response modulation. Notably, TP53 mutations were significantly correlated with high PD1/PDL1 expression. This study provides a comprehensive analysis of PD1/PDL1 expression in lung cancer, uncovering potential biomarkers and highlighting the intricate interplay between PD1/PDL1 and the immune response. The identified upregulated genes, including CD4 and PTPRC, warrant further investigation for their roles in the context of lung cancer and immunotherapy. The study underscores the importance of considering molecular heterogeneity in shaping personalized treatment strategies for lung cancer patients. Limitations, such as the retrospective nature of TCGA data, should be acknowledged.

中文翻译：

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基因组分析揭示了按 PD1/PDL1 表达分层的肺癌患者中免疫相关基因的差异：对免疫治疗疗效的影响

摘要

肺癌仍然是全球癌症相关死亡的主要原因，探索PD1/PDL1免疫疗法等创新治疗方法至关重要。本研究利用癌症基因组图谱 (TCGA) 的综合数据来研究肺癌患者中 PD1/PDL1 的差异表达并探讨其含义。从 TCGA 获得了 1017 名肺癌患者的临床数据、RNA 表达、体细胞突变和拷贝数变异。根据 mRNA 水平将患者分为高 (HE) 和低 (LE) PD1/PDL1 表达组。分析包括差异基因表达、功能富集、蛋白质-蛋白质相互作用网络和突变景观探索。该研究鉴定出 391 个差异表达基因，其中 CD4 和 PTPRC 是 HE 组中表达上调的基因。尽管 HE 组和 LE 组之间的总生存率没有显着差异，但富集分析揭示了与免疫调节信号通路的密切相关性，强调了 PD1/PDL1 在免疫反应调节中的相关性。值得注意的是，TP53 突变与 PD1/PDL1 高表达显着相关。这项研究对肺癌中的 PD1/PDL1 表达进行了全面分析，发现了潜在的生物标志物，并强调了 PD1/PDL1 与免疫反应之间复杂的相互作用。已确定的上调基因，包括 CD4 和 PTPRC，值得进一步研究它们在肺癌和免疫治疗中的作用。该研究强调了在为肺癌患者制定个性化治疗策略时考虑分子异质性的重要性。应该承认 TCGA 数据的局限性等局限性。