Ubiquitination, SUMOylation, and NEDDylation related genes serve as prognostic and therapeutic biomarkers for oral squamous cell carcinoma

Abstract Background Ubiquitination, small ubiquitin‐related modifiers, and NEDDylation are now found to function in cancer biology; however, its role in the oral cancer patients remains unclear. Methods A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of ubiquitin and ubiquitin‐like (UB/UBL) genes. A UB/UBL‐related risk score was developed via correlation analyses, univariate Cox regression, and multivariate Cox regression. Nomogram analysis evaluates the model's prediction performance. The drug sensitivity analysis, immune profiles of UB/UBL‐classified oral squamous cell carcinoma (OSCC) patients, and their related function pathway were investigated, and the role of UB/UBL‐related genes in drug therapy was analyzed. Results A total of six prognostic UB/UBL‐related genes were obtained. PSMD3, PCGF2, and H2BC10 were significantly downregulated in OSCC tissue and associated with longer survival time. OSCC patients in the high‐risk group showed a significantly lower overall survival and enriched in cancer‐related pathways. The prognostic potential of genes associated with UB/UBL was discovered, and patients with high‐risk scores showed an increase of protumor immune infiltrates and a high expression of immune checkpoints. Moreover, the area under the curve of the annual survival rate was 0.616, 0.671, and 0.673, respectively. Besides, patients in the high‐risk group are more sensitive to docetaxel, doxorubicin, and methotrexate therapy. Conclusions We construct a prognosis model for OSCC patients with UB/UBL‐related genes and try to find a new approach to treating oral cancer patients. The UB/UBL‐related signature is helpful in developing new tumor markers, prognostic prediction, and in guiding treatment for OSCC patients.