Potential biomarkers and signaling pathways associated with the pathogenesis of primary salivary gland carcinoma: a bioinformatics study

Salivary gland carcinoma (SGC) is rare cancer, constituting 6% of neoplasms in the head and neck area. The most responsible genes and pathways involved in the pathology of this disorder have not been fully understood. We aimed to identify differentially expressed genes (DEGs), the most critical hub genes, transcription factors, signaling pathways, and biological processes (BPs) associated with the pathogenesis of primary SGC. The mRNA dataset GSE153283 in the Gene Expression Omnibus database was re-analyzed for determining DEGs in cancer tissue of patients with primary SGC compared to the adjacent normal tissue (adjusted p-value < 0.001; |Log2 fold change| > 1). A protein interaction map (PIM) was built, and the main modules within the network were identified and focused on the different pathways and BP analyses. The hub genes of PIM were discovered, and their associated gene regulatory network was built to determine the master regulators involved in the pathogenesis of primary SGC. A total of 137 genes were found to be differentially expressed in primary SGC. The most significant pathways and BPs that were deregulated in the primary disease condition were associated with the cell cycle and fibroblast proliferation procedures. TP53, EGF, FN1, NOTCH1, EZH2, COL1A1, SPP1, CDKN2A, WNT5A, PDGFRB, CCNB1, and H2AFX were demonstrated to be the most critical genes linked with the primary SGC. SPIB, FOXM1, and POLR2A significantly regulate all the hub genes. This study illustrated several hub genes and their master regulators that might be appropriate targets for the therapeutic aims of primary SGC.

Comprehensive Treatment for Major Salivary Gland Carcinoma Based on Intensity-Modulated Radiotherapy with or without Radical Surgery

Background The present study aimed to determine a treatment strategy and Intensity-Modulated Radiotherapy (IMRT) target volume for major salivary gland carcinoma (SGC). Methods Patients with SGC treated at our cancer center between August 2009 and August 2020 were retrospectively reviewed. Results The following primary tumor sites were identified: parotid gland in 61 (69.3%) patients, submandibular gland in 21 (23.9%) patients, and sublingual gland in six (6.8%) patients. Lymphoepithelial carcinoma (LEC) was the most common tumor subtype that accounted for 23.9% of cases. A total of 80 (90.9%) patients received radical surgery combined with postoperative radiotherapy. Eight patients (9.1%) received definitive radiotherapy: six patients with advanced-stage disease received induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT), and two patients with early-stage disease received CCRT. Complete response was observed in these eight patients after treatment completion. The median follow-up time of all patients was 42 months (range: 4–129 months). No patient developed local recurrence. The 5-year overall survival, regional failure-free survival, distant metastasis-free survival, and progression-free survival probabilities were 84.1%, 95.6%, 75.3%, and 75.7%, respectively. Distant metastasis was observed in 18 (20.5%) patients, followed by regional 2 (2.3%) recurrence. Permanent facial nerve injury was confirmed in 31 patients by follow-up. None of the patients experienced facial nerve paralysis in the definitive radiotherapy group. Conclusions LECs may be sensitive to chemoradiotherapy, which may achieve a radical effect and avoid unnecessary surgical injury. IC combined with CCRT is expected to become a new treatment strategy for advanced LECs. The IMRT target volume delineation according to the surgical principles may be a more promising method with good clinical efficacy that is worthy of further study.

Lymph node ratio as a predictor for minor salivary gland cancer in head and neck

Background We investigate whether pathological continuous variables of lymph nodes were related with survival results of carcinomas of minor salivary gland carcinoma in head and neck. Methods Forty-four cases with minor salivary gland carcinoma who underwent both primary resection and neck dissection were retrospectively enrolled. The pathological continuous variables were evaluated by the number of positive lymph nodes, lymph node ratio, and log odds of positive lymph nodes. Receiver operating curve analysis was used for the cut-off values of the carcinoma-specific death. Log-rank test and Cox’s proportional hazards model were used for uni−/multi-variate survival analyses adjusting for pathological stage, respectively. Results Lymph node ratio = 0.05 as well as log odds of positive lymph nodes = − 2.73 predicted the carcinoma-specific death. Both lymph node ratio and log odds of positive lymph nodes were significantly related with survival outcomes by the univariate analysis. Lymph node ratio ≥ 0.05 was associated with shorter disease-specific (hazard ratio = 7.90, 95% confidence interval = 1.54–57.1), disease-free (hazard ratio = 4.15, 95% confidence interval = 1.48–11.2) and overall (hazard ratio = 4.84, 95% confidence interval = 1.05–24.8) survival in the multivariate analysis. Conclusion A higher lymph node ratio of minor salivary gland carcinoma is a predictor of shorter survival results.