» Articles » PMID: 39286258

Multi-omics Landscape of Interferon-stimulated Gene OASL Reveals a Potential Biomarker in Pan-cancer: from Prognosis to Tumor Microenvironment

Overview
Journal Front Immunol
Date 2024 Sep 17
PMID 39286258
Authors
Affiliations
Soon will be listed here.
Abstract

Background: OASL (Oligoadenylate Synthetase-Like), an interferon-induced protein in the OAS family, plays a significant role in anti-viral response. Studies have demonstrated its association with prognosis of certain tumors. However, the mechanism through which OASL affects tumors is unclear. A systemic pan-cancer study of OASL needs to be illustrated.

Methods: Analysis of OASL expression across 33 tumors was conducted utilizing TCGA, GTEx and CPTAC databases. COX and Log-Rank regressions were employed to calculate the prognosis. We validated the impact of OASL on apoptosis, migration, and invasion in pancreatic cancer cell lines. Moreover, we employed seven algorithms in bulk data to investigate the association of OASL expression and immune cell infiltration within tumor immune microenvironment (TIME) and ultimately validated at single-cell transcriptome level.

Results: We discovered elevated expression of OASL and its genetic heterogeneity in certain tumors, which link closely to prognosis. Validation experiments were conducted in PAAD and confirmed these findings. Additionally, OASL regulates immune checkpoint ligand such as programmed death ligand 1 (PD-L1), through IFN-γ/STAT1 and IL-6/JAK/STAT3 pathways in tumor cells. Meanwhile, OASL affects macrophages infiltration in TIME. By these mechanisms OASL could cause dysfunction of cytotoxic T lymphocytes (CTLs) in tumors.

Discussion: Multi-omics analysis reveals OASL as a prognostic and immunological biomarker in pan-cancer.

Citing Articles

Spatial transcriptome reveals histology-correlated immune signature learnt by deep learning attention mechanism on H&E-stained images for ovarian cancer prognosis.

Ng C, Wong K, Lawson B, Ferri-Borgogno S, C Mok S J Transl Med. 2025; 23(1):113.

PMID: 39856778 PMC: 11761186. DOI: 10.1186/s12967-024-06007-8.


Investigating the clinical significance of OAS family genes in breast cancer: an in vitro and in silico study.

Lu J, Yang L, Yang X, Chen B, Liu Z Hereditas. 2024; 161(1):50.

PMID: 39633486 PMC: 11619215. DOI: 10.1186/s41065-024-00353-9.

References
1.
Yamaguchi H, Hsu J, Yang W, Hung M . Mechanisms regulating PD-L1 expression in cancers and associated opportunities for novel small-molecule therapeutics. Nat Rev Clin Oncol. 2022; 19(5):287-305. DOI: 10.1038/s41571-022-00601-9. View

2.
Pang K, Shi Z, Wei L, Dong Y, Ma Y, Wang W . Research progress of therapeutic effects and drug resistance of immunotherapy based on PD-1/PD-L1 blockade. Drug Resist Updat. 2022; 66:100907. DOI: 10.1016/j.drup.2022.100907. View

3.
DallOlio F, Marabelle A, Caramella C, Garcia C, Aldea M, Chaput N . Tumour burden and efficacy of immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2021; 19(2):75-90. DOI: 10.1038/s41571-021-00564-3. View

4.
Stratton M, Campbell P, Futreal P . The cancer genome. Nature. 2009; 458(7239):719-24. PMC: 2821689. DOI: 10.1038/nature07943. View

5.
Benci J, Johnson L, Choa R, Xu Y, Qiu J, Zhou Z . Opposing Functions of Interferon Coordinate Adaptive and Innate Immune Responses to Cancer Immune Checkpoint Blockade. Cell. 2019; 178(4):933-948.e14. PMC: 6830508. DOI: 10.1016/j.cell.2019.07.019. View