Genetic Cross-Talk between Oral Squamous Cell Carcinoma and Type 2 Diabetes: The Potential Role of Immunity

Abstract

Background. This bioinformatics study was aimed at evaluating type 2 diabetes (T2D) and oral squamous cell carcinoma (OSCC) with regard to related immune cells and prognosis. Methods. We downloaded the data on OSCC from TCGA and for T2D from GEO database. Differentially expressed genes were analyzed, i.e., for OSCC genes with p value < 0.01 , log 2 FC > 0 ; and for T2D, genes with p value < 0.05 , log 2 FC > 0 . The intersected genes between OSCC and T2D were cross-talk genes. The expression values of immune-related genes in case samples in OSCC and T2D were assessed and underwent multivariate and univariate analysis (Cox-PH model). The intersection between the immune genes and cross-talk genes was taken and further analyzed by recursive feature elimination (RFE), survival analysis, and ROC analysis. Results. 1008 cross-talk genes were acquired, including 28 common upregulated, 440 common downregulated, and 540 differently regulated DEGs. We extracted the gene expression value of 782 immune-related genes, of which seven increased immune cells were obtained. From the results, plasmacytoid dendritic cells and effector memory CD8 T cells were highly negatively correlated in both OSCC and T2D. After estimating a low- and high-risk model for survival, we found that activated dendritic cell was significantly different between high and low groups ( p = 0.0095 ), followed by plasmacytoid dendritic cell. We integrated DE_Immune genes set 1 and DE_Immune genes set 2 and eight key immune-related cross-talk genes (C1QC, ABCD1, NOS2, PDIA4, IL1RN, ALOX15, CSE1L, and PSMC4) were evaluated. After ROC analysis, we obtained that ABCD1, C1QC, CSE1L, and PSMC4 had higher classification and prediction effects on OSCC and T2D. Conclusion. This study revealed a close relationship between T2D and OSCC. Thereby, plasmacytoid dendritic cell and activated dendritic cell-related genes were associated with the survival of T2D-related OSCC, while ABCD1, C1QC, CSE1L, and PSMC4 were the most important immune-related cross-talk genes.

Investigation of the Proteasome 26S Subunit, ATPase Family Genes as Potential Prognostic Biomarkers and Therapeutic Targets for Hepatocellular Carcinoma

“…23 For example, PSMC4 gene expression was found to be upregulated in a wide variety of human tumor tissues, including pituitary adenomas, oral squamous cell carcinoma, laryngeal cancer, breast cancer, and prostate cancer. [24][25][26][27][28] Not only that, PSMCs are considered to act as oncogenes and contribute to poor prognosis in multiple cancers. A previous study reported that PSMC1 promotes the proliferation and migration of lung adenocarcinoma cells and is related to poor prognosis in patients with lung adenocarcinoma.…”

The prognostic value of 19S ATPase proteasome subunits in acute myeloid leukemia and other forms of cancer

“…Genome editing or small-molecule mediated inhibition of DYRK2 significantly bypassed bortezomib resistance in both multiple myeloma and breast cancer cells ( 69 ). PSMC4 is also considered a biomarker in endometrial cancer ( 70–72 ), breast cancer ( 60 ), hepatocellular carcinoma ( 73 ), oral squamous cell carcinoma ( 74 ), and laryngeal carcinoma ( 75 ). Combined with our data in the present study, PSMC4 may be a novel biomarker and therapeutic target for drug-resistant cancer patients demonstrating high levels of PSMC4 expression.…”

PSMC4 promotes prostate carcinoma progression by regulating the CBX3–EGFR‐PI3K‐AKT‐mTOR pathway

“…PSMC4 has been shown to be essential for the normal function of the proteasome in a variety of cellular processes, including DNA repair, cell cycle regulation and protein regulation. In addition, PSMC4 can also regulate the progression of multiple types of cancer, including breast cancer, 8 endometrial cancer, 9,10 PCa, 11 oral squamous cell carcinoma 12 . Studies have showed that high level of PSMC4 was positively correlated with shorter survival in breast cancer 8 .…”

“…In addition, PSMC4 can also regulate the progression of multiple types of cancer, including breast cancer, 8 endometrial cancer, 9 , 10 PCa, 11 oral squamous cell carcinoma. 12 Studies have showed that high level of PSMC4 was positively correlated with shorter survival in breast cancer. 8 Moreover, PSMC4 can serve as one of the best reference genes for type 1 endometrial cancer.…”