Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell Carcinoma

Abstract

Background. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated. Materials and Methods. Gene differential analysis was used to measure the differences of gene expression between the groups. Correlation analysis was used to assess the association between the gene expression levels and immune-related risk score/DNA methylation levels. The gene set enrichment analysis (GSEA) was used to identify the pathways or cell types enriched by those identified differentially expressed genes (DEGs). Results. In this study, we identified four immune-related gene signatures, including CTSG, TNFRSF4, LCORL, and PLAU, that were significantly associated with the overall survival in OSCC patients from the Cancer Genome Atlas (TCGA) OSCC cohort. Moreover, these four immune-related signatures were differentially expressed between the OSCC and nontumor tissues. The two groups (high and low risk) stratified by the immune-related risk scores had significantly different OS and mortality rates. The gene expression patterns and prognostic values of these immune-related signatures were also verified in two independent validation cohorts. Furthermore, the downregulated genes in the high-risk group (which were also upregulated in the low-risk group) were significantly enriched in the cell type-specific signatures of type 2 T helper cell (Th2), plasmacytoid dendritic cell (pDC), and memory B cell. In contrast, the upregulated genes in the high-score group were enriched in growth factor receptor-related signaling pathways, such as the VEGFA-VEGFR2 signaling pathway, PI3K-Akt signaling pathway, focal adhesion-PI3K-Akt-mTOR signaling pathway, and PDGF pathway, suggesting that those pathways were inversely correlated with immune cell infiltration. Conclusion. In summary, the immune-related signatures had the potential for predicting the risk of OSCC patients. Moreover, the present study also improved our understanding of the association between the growth factor receptor pathways and immune cell infiltration in OSCC.

Immune‐related gene signature predicts clinical outcomes and immunotherapy response in acute myeloid leukemia

“…Our study has many highlights. Several researches previously have proposed certain risk signatures based on various characteristics, in hopes of stratifying the prognosis of cancer patients 53,54 . Zheng et al have identified a signature of seven‐lncRNA to predict the OS of patients with AML 6 .…”

“…Several researches previously have proposed certain risk signatures based on various characteristics, in hopes of stratifying the prognosis of cancer patients. 53 , 54 Zheng et al have identified a signature of seven‐lncRNA to predict the OS of patients with AML. 6 Compared with those studies, the WGCNA used in our study has a unique advantage in dealing with gene expression data because it allows us to gain insight into the connection between coexpression modules and clinical characteristics of the disease.…”

A Novel Immune-Related Gene Signature to Identify the Tumor Microenvironment and Prognose Disease Among Patients With Oral Squamous Cell Carcinoma Patients Using ssGSEA: A Bioinformatics and Biological Validation Study

“…In addition, CTSG is associated with tumor angiogenesis and metastasis, participating in host defense and neutrophil-related immune responses, and serving as a target of immunotherapy for acute myeloid leukemia (AML) ( 38 ). CTSG is also closely related to the survival of several cancer types, including soft tissue sarcoma, muscular invasive bladder cancer, and lymph node-negative breast cancer ( 39 ), and is a potential immune-related biomarker for OSCC ( 40 ). The current study showed that CTSG could inhibit the proliferation, migration, invasion, and colony formation of SCC15 cells in vitro , confirming that CTSG plays a key role in tumorigenesis and progression.…”

CTSG Suppresses Colorectal Cancer Progression through Negative Regulation of Akt/mTOR/Bcl2 Signaling Pathway

“…Gormley et al 25 showed that CTSS could be a diagnostic marker for CRC and may increase 5-Fu and folic acid therapeutic sensitivity. Many studies have indicated that CTSG, a member of the Cathepsin family, functions as a cancer suppressor in many tumors, inhibiting the malignant features and cancers development, like breast, bladder, oral squamous cell cancer, and acute myeloid leukemia 26 - 29 . However, CTSG role in CRC oncogenesis has rarely been studied.…”