建立一种基于免疫相关基因的预后模型,并确认BIRC5作为肺腺癌患者的潜在生物标志物。
Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients.
发表日期:2023 Sep 23
作者:
Qianhe Ren, Qifan Li, Chenye Shao, Pengpeng Zhang, Zhuangzhuang Hu, Jun Li, Wei Wang, Yue Yu
来源:
Cellular & Molecular Immunology
摘要:
肺腺癌(LUAD)是一种极具恶性的肿瘤,发病率迅速增加且预后差。免疫疗法已被证实是肺腺癌的一种有希望的治疗方式。此外,一种基于免疫基因的预后模型可以实现早期诊断和准确预后预测的目的。利用免疫相关mRNA(IRmRNAs)构建了一个预后模型,将患者分为高风险和低风险组,并使用一种正态图评估了我们模型的预测能力。进一步探索了不同风险组别之间的总体生存率(OS)、肿瘤突变景观和肿瘤微环境的差异。此外,对包含在预后模型中的免疫基因进行了单细胞RNA测序,以研究这些免疫基因在不同细胞中的表达。最后,通过体外实验验证了BIRC5的功能。不同风险组的患者在OS、途径活性、免疫细胞浸润、突变模式和免疫反应方面存在显著差异。单细胞RNA测序揭示了BIRC5在T细胞中的表达水平显著高。细胞实验证明,BIRC5敲除显著抑制了LUAD细胞的增殖。该模型可作为肺腺癌的预后、分子和治疗预测中的工具变量,为肺腺癌患者的最佳临床实践指南提供新视角。© 2023. BioMed Central Ltd., Springer Nature的一部分。
Lung adenocarcinoma (LUAD) is an extraordinarily malignant tumor, with rapidly increasing morbidity and poor prognosis. Immunotherapy has emerged as a hopeful therapeutic modality for lung adenocarcinoma. Furthermore, a prognostic model (based on immune genes) can fulfill the purpose of early diagnosis and accurate prognostic prediction.Immune-related mRNAs (IRmRNAs) were utilized to construct a prognostic model that sorted patients into high- and low-risk groups. Then, the prediction efficacy of our model was evaluated using a nomogram. The differences in overall survival (OS), the tumor mutation landscape, and the tumor microenvironment were further explored between different risk groups. In addition, the immune genes comprising the prognostic model were subjected to single-cell RNA sequencing to investigate the expression of these immune genes in different cells. Finally, the functions of BIRC5 were validated through in vitro experiments.Patients in different risk groups exhibited sharply significant variations in OS, pathway activity, immune cell infiltration, mutation patterns, and immune response. Single-cell RNA sequencing revealed that the expression level of BIRC5 was significantly high in T cells. Cell experiments further revealed that BIRC5 knockdown markedly reduced LUAD cell proliferation.This model can function as an instrumental variable in the prognostic, molecular, and therapeutic prediction of LUAD, shedding new light on the optimal clinical practice guidelines for LUAD patients.© 2023. BioMed Central Ltd., part of Springer Nature.