Identification and validation of hypoxia-derived gene signatures to predict clinical outcomes and therapeutic responses in stage I lung adenocarcinoma patients

Shi, Run; Bao, Xuanwen; Unger, Kristian; Sun, Jing; Lu, Shun; Manapov, Farkhad; Wang, Xuanbin; Belka, Claus und Li, Minglun (2021): Identification and validation of hypoxia-derived gene signatures to predict clinical outcomes and therapeutic responses in stage I lung adenocarcinoma patients. In: Theranostics, Bd. 11, Nr. 10: S. 5061-5076

Abstract

Rationale: The current tumour-node-metastasis (TNM) staging system is insufficient for precise treatment decision-making and accurate survival prediction for patients with stage I lung adenocarcinoma (LUAD). Therefore, more reliable biomarkers are urgently needed to identify the high-risk subset in stage I patients to guide adjuvant therapy. Methods: This study retrospectively analysed the transcriptome profiles and clinical parameters of 1,400 stage I LUAD patients from 14 public datasets, including 13 microarray datasets from different platforms and 1 RNA-Seq dataset from The Cancer Genome Atlas ( TCGA). A series of bioinformatic and machine learning approaches were combined to establish hypoxia-derived signatures to predict overall survival (OS) and immune checkpoint blockade (ICB) therapy response in stage I patients. In addition, enriched pathways, genomic and copy number alterations were analysed in different risk subgroups and compared to each other. Results: Among various hallmarks of cancer, hypoxia was identified as a dominant risk factor for overall survival in stage I LUAD patients. The hypoxia-related prognostic risk score (HPRS) exhibited more powerful capacity of survival prediction compared to traditional clinicopathological features, and the hypoxia-related immunotherapeutic response score (HIRS) outperformed conventional biomarkers for ICB therapy. An integrated decision tree and nomogram were generated to optimize risk stratification and quantify risk assessment. Conclusions: In summary, the proposed hypoxia-derived signatures are promising biomarkers to predict clinical outcomes and therapeutic responses in stage I LUAD patients.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1838-7640
• Sprache: Englisch