Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients

Abstract Background 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 pur...

Full description

Bibliographic Details
Main Authors: Qianhe Ren, Qifan Li, Chenye Shao, Pengpeng Zhang, Zhuangzhuang Hu, Jun Li, Wei Wang, Yue Yu
Format: Article
Language:English
Published: BMC 2023-09-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-023-11249-8
_version_ 1797452283933360128
author Qianhe Ren
Qifan Li
Chenye Shao
Pengpeng Zhang
Zhuangzhuang Hu
Jun Li
Wei Wang
Yue Yu
author_facet Qianhe Ren
Qifan Li
Chenye Shao
Pengpeng Zhang
Zhuangzhuang Hu
Jun Li
Wei Wang
Yue Yu
author_sort Qianhe Ren
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusion 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.
first_indexed 2024-03-09T15:05:33Z
format Article
id doaj.art-09ec90bf678a465f9531139c745122ec
institution Directory Open Access Journal
issn 1471-2407
language English
last_indexed 2024-03-09T15:05:33Z
publishDate 2023-09-01
publisher BMC
record_format Article
series BMC Cancer
spelling doaj.art-09ec90bf678a465f9531139c745122ec2023-11-26T13:37:37ZengBMCBMC Cancer1471-24072023-09-0123112010.1186/s12885-023-11249-8Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patientsQianhe Ren0Qifan Li1Chenye Shao2Pengpeng Zhang3Zhuangzhuang Hu4Jun Li5Wei Wang6Yue Yu7Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, Shuyang First People’s HospitalDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s12885-023-11249-8lung adenocarcinomaImmune genesRisk signaturePrognosisTumor mutation burdenImmunotherapy
spellingShingle Qianhe Ren
Qifan Li
Chenye Shao
Pengpeng Zhang
Zhuangzhuang Hu
Jun Li
Wei Wang
Yue Yu
Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients
BMC Cancer
lung adenocarcinoma
Immune genes
Risk signature
Prognosis
Tumor mutation burden
Immunotherapy
title Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients
title_full Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients
title_fullStr Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients
title_full_unstemmed Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients
title_short Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients
title_sort establishing a prognostic model based on immune related genes and identification of birc5 as a potential biomarker for lung adenocarcinoma patients
topic lung adenocarcinoma
Immune genes
Risk signature
Prognosis
Tumor mutation burden
Immunotherapy
url https://doi.org/10.1186/s12885-023-11249-8
work_keys_str_mv AT qianheren establishingaprognosticmodelbasedonimmunerelatedgenesandidentificationofbirc5asapotentialbiomarkerforlungadenocarcinomapatients
AT qifanli establishingaprognosticmodelbasedonimmunerelatedgenesandidentificationofbirc5asapotentialbiomarkerforlungadenocarcinomapatients
AT chenyeshao establishingaprognosticmodelbasedonimmunerelatedgenesandidentificationofbirc5asapotentialbiomarkerforlungadenocarcinomapatients
AT pengpengzhang establishingaprognosticmodelbasedonimmunerelatedgenesandidentificationofbirc5asapotentialbiomarkerforlungadenocarcinomapatients
AT zhuangzhuanghu establishingaprognosticmodelbasedonimmunerelatedgenesandidentificationofbirc5asapotentialbiomarkerforlungadenocarcinomapatients
AT junli establishingaprognosticmodelbasedonimmunerelatedgenesandidentificationofbirc5asapotentialbiomarkerforlungadenocarcinomapatients
AT weiwang establishingaprognosticmodelbasedonimmunerelatedgenesandidentificationofbirc5asapotentialbiomarkerforlungadenocarcinomapatients
AT yueyu establishingaprognosticmodelbasedonimmunerelatedgenesandidentificationofbirc5asapotentialbiomarkerforlungadenocarcinomapatients