Development and validation of a hypoxia-associated signature for lung adenocarcinoma
Affiliation
Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, M20 4BX, UK. Department Clinical Oncology, Christie NHS Foundation Trust Hospital, Manchester, M204BX, UK. Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester, M20 4BX, UK. Catharine.West@manchester.ac.uk.Issue Date
2022
Metadata
Show full item recordAbstract
Hypoxia is common in non-small cell lung cancer (NSCLC) and an attractive therapeutic target. As hypoxia-targeting treatments are effective in patients with the most hypoxic tumours, we aimed to develop a lung adenocarcinoma (LUAD) hypoxia-related gene expression signature. RNAseq was used to identify genes significantly differentially expressed under hypoxia (1% O2) in four LUAD cell lines. Identified genes were used for unsupervised clustering of a TCGA-LUAD training dataset (n=252) and in a machine learning approach to build a hypoxia-related signature. Thirty-five genes were upregulated in common in three of the four lines and reduced in the training cohort to a 28-gene signature. The signature was prognostic in the TCGA training (HR 2.12, 95% CI 1.34–3.37, p = 0.0011) and test (n = 250; HR 2.13, 95% CI 1.32–3.45, p = 0.0016) datasets. The signature was prognostic for overall survival in a meta-analysis of nine other datasets (n=1257; HR 2.08, 95% CI 1.60–2.70, p<0.0001). The 28-gene LUAD hypoxia related signature can be taken forward for further validation using a suitable gene expression platform.Citation
Lane B, Khan MT, Choudhury A, Salem A, West CML. Development and validation of a hypoxia-associated signature for lung adenocarcinoma. Vol. 12, Scientific Reports. Springer Science and Business Media LLC; 2022.Journal
Science ReportsDOI
10.1038/s41598-022-05385-7PubMed ID
35079065Additional Links
https://dx.doi.org/10.1038/s41598-022-05385-7Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41598-022-05385-7