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Article

Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study

School of Medicine, University of Central Lancashire, Preston PR1 2HE, UK
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Academic Editor: Andrew Phillip West
Int. J. Mol. Sci. 2021, 22(11), 5478; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115478
Received: 28 April 2021 / Revised: 17 May 2021 / Accepted: 21 May 2021 / Published: 22 May 2021
(This article belongs to the Special Issue Molecular Drivers of Responsiveness to Cancer Immunotherapy)
Immune checkpoint blockade targeting PD-1 (PDCD1)/PD-L1 (CD274) is increasingly used for multiple cancers. However, efficacy and adverse-related events vary significantly. This bioinformatic study interrogated molecular differences pertaining to PDCD1/CD274 and their correlated genes on a pan-cancer basis to identify differences between cancer types. Patient RNA-seq data from fifteen cancer types were accessed on cBioPortal to determine the role of PDCD1/CD274 in patient survival and to identify positively and negatively correlated genes, which were also assessed for clinical relevance. Genes correlating with PDCD1/CD274 across multiple cancers were taken forward for drug repurposing via DRUGSURV and microRNA analysis using miRDB and miRabel. MicroRNAs were also screened for clinical relevance using OncomiR. Forty genes were consistently correlated with PDCD1/CD274 across multiple cancers, with the cancers themselves exhibiting a differential role for the correlated genes in terms of patient survival. Esophageal and renal cancers in particular stood out in this regard as having a unique survival profile. Forty-nine putative microRNAs were identified as being linked to the PDCD1/CD274 network, which were taken forward and further assessed for clinical relevance using OncomiR and previously published literature. One hundred and thirty significant survival associations for 46 microRNAs across fourteen groups of cancers were identified. Finally, a total of 23 putative repurposed drugs targeting multiple components of the PDCD1/CD274 network were identified, which may represent immunotherapeutic adjuvants. Taken together, these results shed light on the varying PDCD1/CD274 networks between individual cancers and signpost a need for more cancer-specific investigations and treatments. View Full-Text
Keywords: immunotherapy; immune checkpoint blockade; cBioPortal; bioinformatics; computational biology; survival analysis; OncomiR; microRNAs immunotherapy; immune checkpoint blockade; cBioPortal; bioinformatics; computational biology; survival analysis; OncomiR; microRNAs
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MDPI and ACS Style

Kannan, S.; O’Connor, G.M.; Bakker, E.Y. Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study. Int. J. Mol. Sci. 2021, 22, 5478. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115478

AMA Style

Kannan S, O’Connor GM, Bakker EY. Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study. International Journal of Molecular Sciences. 2021; 22(11):5478. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115478

Chicago/Turabian Style

Kannan, Siddarth, Geraldine M. O’Connor, and Emyr Y. Bakker 2021. "Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study" International Journal of Molecular Sciences 22, no. 11: 5478. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115478

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