Background Cisplatin-based chemotherapy is a mainstay treatment for head and neck squamous cell carcinoma (HNSC); however, resistance to cisplatin contributes substantially to poor clinical outcomes. Identifying biomarkers associated with cisplatin response may improve prognostic assessment and treatment selection.
Methods We retrospectively analyzed The Cancer Genome Atlas (TCGA)-HNSC dataset to evaluate the association between microtubule associated scaffold protein 1 (MTUS1) expression and clinical outcomes, with particular emphasis on patients who were cisplatin-treated. Survival analysis was performed using the Kaplan-Meier curves, and differential expression analysis was conducted separately by comparing patients in disease-specific survival (DSS)-living and DSS-deceased groups. MTUS1 messenger RNA and protein levels were examined in cisplatin-sensitive oral cancer cell lines and their paired cisplatin-resistant counterparts using quantitative reverse transcription polymerase chain reaction and western blotting. Functional relevance was assessed by small interfering RNA-mediated MTUS1 knockdown in primary oral squamous cell carcinoma organoids.
Results MTUS1 protein expression was significantly lower in HNSC tumors than in non-tumor tissues. In the overall TCGA-HNSC cohort, MTUS1 expression was not significantly associated with survival. However, in patients who were cisplatin-treated, higher MTUS1 expression was significantly associated with more favorable DSS. MTUS1 expression was consistently lower in cisplatin-resistant oral cancer cell lines than in their paired cisplatin-sensitive counterparts. Functional experiments further suggested that reduced MTUS1 expression is associated with decreased cisplatin sensitivity and a resistant phenotype.
Conclusion MTUS1 expression may be associated with clinical outcomes in patients with cisplatin-treated HNSC and is related to cisplatin responsiveness. These findings suggest a role for MTUS1 as a candidate treatment-relevant biomarker and highlight the value of integrating public omics data with experimental validation.
BACKGROUND Lung cancer-associated hypercalcemia is one of the most disabling and life-threatening paraneoplastic desorders. Humoral hypercalcemia is responsible for most lung cancer-associated hypercalcemia. Patients with hypercalcemia are usually in the advenced atage with obvious bulky tumor and carry a poor prognosis. MATERIALS AND METHODS: Total 29 patients satisfied the following criteria: histologically proven primary lung cancer, corrected calcium level> or =10.5 mg/dL, and symptons which could possibly be attributed to hypercalcemia. In this retrospective study, we evalluated the various clinical aspects of hypercalcemia, in relation to cancer stage, histologic cell type, mass size, bone metastasis, performance status, and other possible characteristics RESULTS: Total 29 lung cancer patients with hypercalcemia were studied, and most of them had squamous cell carcinoma in their histologic finding. The incidence of hypercalcemia was significantly higher between 50 and 69 years of age, and in the advancement of cancer stage. Although serum calcium level showed positive correlation with mass size, performance statusm and bone ore frequent in the patients with higher serum calcium level. There were no differences in effectiveness among therapeutic regimens. Hypercalcemia was more frequently in the later stage of disease than during the initial diagnosis of lung cancer. Most of the patients died within 1 month after development of hypercalcemia. CONCLUSION: We concluded that hypercalcemia in lung cancer is related to extremely poor prognosis, and may be one of the causes of drath and should be treated aggressively to prevent sudden deterioration or death.