基因组剖析揭示了肺癌患者按 PD1/PDL1 表达分层的免疫相关基因差异:免疫疗法疗效的意义。

IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Applied Genetics Pub Date : 2024-02-16 DOI:10.1007/s13353-024-00841-8
Zhifeng Ye, Ting Huang, Keke Hu, HeRan Zhou, Ling Huang, Lu Wang
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引用次数: 0

摘要

肺癌仍然是全球癌症相关死亡的主要原因,因此探索创新治疗方法(如 PD1/PDL1 免疫疗法)至关重要。本研究利用癌症基因组图谱(TCGA)的综合数据研究肺癌患者中 PD1/PDL1 的差异表达并探讨其影响。研究人员从 TCGA 中获得了 1017 例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 PD1/PDL1 高表达组(HE)和低表达组(LE)。分析包括差异基因表达、功能富集、蛋白-蛋白相互作用网络和突变景观探索。研究发现了391个差异表达基因,其中CD4和PTPRC是HE组中上调的基因。虽然HE组和LE组的总生存率没有明显差异,但富集分析显示,HE组和LE组与免疫调节信号通路密切相关,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的高表达显著相关。这项研究全面分析了肺癌中PD1/PDL1的表达,发现了潜在的生物标记物,并强调了PD1/PDL1与免疫反应之间错综复杂的相互作用。已发现的上调基因,包括 CD4 和 PTPRC,值得进一步研究它们在肺癌和免疫疗法中的作用。这项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。应当承认研究的局限性,如TCGA数据的回顾性。
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Genomic Profiling Reveals Immune-Related Gene Differences in Lung Cancer Patients Stratified by PD1/PDL1 Expression: Implications for Immunotherapy Efficacy.

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.

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来源期刊
Journal of Applied Genetics
Journal of Applied Genetics 生物-生物工程与应用微生物
CiteScore
4.30
自引率
4.20%
发文量
62
审稿时长
6-12 weeks
期刊介绍: The Journal of Applied Genetics is an international journal on genetics and genomics. It publishes peer-reviewed original papers, short communications (including case reports) and review articles focused on the research of applicative aspects of plant, human, animal and microbial genetics and genomics.
期刊最新文献
Correction to: Diallel analysis of common bean (Phaseolus vulgaris L.) genotypes for seed dietary fibre, carbohydrate, calcium and phosphorus contents. Retraction Note: A new DNA sequence entropy-based Kullback-Leibler algorithm for gene clustering. Peptidylprolyl isomerase D circular RNA sensitizes breast cancer to trastuzumab through remodeling HER2 N4-acetylcytidine modification. The role of multidisciplinary diagnostic and therapeutic model of care in Lamb-Shaffer syndrome - case report. Uncovering the role of aquaporin and chromobox family members as potential biomarkers in head and neck squamous cell carcinoma via integrative multiomics and in silico approach.
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