Shanxi Provincial Key Laboratory of Kidney Disease, Shanxi Provincial People's Hospital of Shanxi Medical University, Taiyuan, 030012, Shanxi, China.
Department of Nephrology, Shanxi Provincial People's Hospital (Fifth Hospital of Shanxi Medical University), Taiyuan, 030012, China.
Sci Rep. 2024 Jan 10;14(1):964. doi: 10.1038/s41598-023-50787-w.
Immunotherapy has emerged as a promising modality for addressing advanced or conventionally drug-resistant malignancies. When it comes to lung adenocarcinoma (LUAD), T cells have demonstrated significant influence on both antitumor activity and the tumor microenvironment. However, their specific contributions remain largely unexplored. This investigation aimed to delineate molecular subtypes and prognostic indicators founded on T cell marker genes, thereby shedding light on the significance of T cells in LUAD prognosis and precision treatment. The cellular phenotypes were identified by scrutinizing the single-cell data obtained from the GEO repository. Subsequently, T cell marker genes derived from single-cell sequencing analyses were integrated with differentially expressed genes from the TCGA repository to pinpoint T cell-associated genes. Utilizing Cox analysis, molecular subtypes and prognostic signatures were established and subsequently verified using the GEO dataset. The ensuing molecular and immunological distinctions, along with therapy sensitivity between the two sub-cohorts, were examined via the ESTIMATE, CIBERSORT, and ssGSEA methodologies. Compartmentalization, somatic mutation, nomogram development, chemotherapy sensitivity prediction, and potential drug prediction analyses were also conducted according to the risk signature. Additionally, real-time qPCR and the HPA database corroborated the mRNA and protein expression patterns of signature genes in LUAD tissues. In summary, this research yielded an innovative T cell marker gene-based signature with remarkable potential to prognosis and anticipate immunotherapeutic outcomes in LUAD patients.
免疫疗法已成为治疗晚期或传统药物耐药性恶性肿瘤的一种有前途的方法。在肺腺癌 (LUAD) 中,T 细胞对肿瘤的抗肿瘤活性和肿瘤微环境都有显著影响。然而,其具体贡献在很大程度上仍未得到探索。本研究旨在基于 T 细胞标记基因描绘分子亚型和预后指标,从而阐明 T 细胞在 LUAD 预后和精准治疗中的意义。通过仔细研究从 GEO 存储库获得的单细胞数据来确定细胞表型。随后,将单细胞测序分析中获得的 T 细胞标记基因与 TCGA 存储库中的差异表达基因整合,以确定 T 细胞相关基因。利用 Cox 分析建立分子亚型和预后特征,并使用 GEO 数据集进行后续验证。通过 ESTIMATE、CIBERSORT 和 ssGSEA 方法检查两个亚群之间的后续分子和免疫学差异以及治疗敏感性。还根据风险特征进行了分区、体细胞突变、列线图开发、化疗敏感性预测和潜在药物预测分析。此外,实时 qPCR 和 HPA 数据库证实了 LUAD 组织中特征基因的 mRNA 和蛋白表达模式。总之,这项研究产生了一种创新的基于 T 细胞标记基因的签名,具有显著的潜力,可以对 LUAD 患者的预后和预测免疫治疗结果。