Objective: This study aimed to identify the programmed death ligand-1 (PDL1, also
termed as CD274) and its positively correlated immune checkpoint genes (ICGs) and
to determine the immune subtypes of CD274-centered ICG combinations in oral and
squamous cell carcinoma (OSCC).
Materials and Methods: Firstly, the 95 ICGs obtained via literature reviews were
identified in the Cancer Genome Atlas (TCGA) database in relation to OSCC, and such
88 ICG expression profiles were extracted. ICGs positively correlated with CD274 were
utilized for subsequent analysis. The relationship between ICGs positively correlated with
CD274 and immunotherapy biomarkers (tumor mutation burden (TMB), and adaptive
immune resistance pathway genes) was investigated, and the relationships of these
genes with OSCC clinical features were explored. The prognostic values of CD274 and
its positively correlated ICGs and also their associated gene pairs were revealed using
the survival analysis.
Results: Eight ICGs, including CTLA4, ICOS, TNFRSF4, CD27, B- and T-lymphocyte
attenuator (BTLA), ADORA2A, CD40LG, and CD28, were found to be positively
correlated with CD274. Among the eight ICGs, seven ICGs (CTLA4, ICOS, TNFRSF4,
CD27, BTLA, CD40LG, and CD28) were significantly negatively correlated with TMB.
The majority of the adaptive immune resistance pathway genes were positively
correlated with ICGs positively correlated with CD274. The survival analysis utilizing
the TCGA-OSCC data showed that, although CD274 was not significantly associated
with overall survival (OS), the majority of ICGs positively correlated with CD274
(BTLA, CD27, CTLA4, CD40LG, CD28, ICOS, and TNFRSF4) were significantly
correlated with OS, whereby their low-expression predicted a favorable prognosis.
The survival analysis based on the gene pair subtypes showed that the combination
subtypes of CD274_low/BTLA_low, CD274_low/CD27_low, CD274_low/CTLA4_low,
CD8A_high/BTLA_low, CD8A_high/CD27_low, and CD8A_high/CTLA4_low predicted
favorable OS.
Conclusion: The results in this study provide a theoretical basis for prognostic immune
subtyping of OSCC and highlight the importance of developing future immunotherapeutic
strategies for treating oral cancer.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84563 |
| Date | 05 April 2023 |
| Creators | Yu, Yang, Tang, Huiwen, Francheschi, Debora, Mujagond, Prabhakar, Acharya, Aneesha, Deng, Yupei, Lethaus, Bernd, Savkovic, Vuk, Zimmerer, Rüdiger, Ziebolz, Dirk, Li, Simin, Schmalz, Gerhard |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2296-858X, 759605 |
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