PCMT1 as a prognostic marker in breast cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) is one of the most aggressive cancers in women, therefore it is necessary to determine novel prognostic markers to estimate survival and advancement the treatment of the disease. Recently, PCMT1, a protein mediating TNBC immune infiltration, has gained attention as a potential therapeutic target. The aim of the study was to demonstrate the relationship between PCMT1 protein overexpression as a prognostic indicator for patients with TNBC cancer and patient survival. MATERIALS AND METHODS: The study included 64 samples collected from 64 TNBC patients. We used the ImageJ software with the IHC Profiler driver for image analysis. To improve the reliability of the results, we expanded the analysis by including The Cancer Genome Atlas cohort. RESULTS: We observed strong PCMT1 immunoreactivity in breast cancer samples and PCMT1 expression in TNBC was significantly higher than in the control group. Patients with high PCMT1 expression had a significantly lower overall survival rate (60.62% vs. 90.35%, respectively) than patients with low PCMT1 expression. In our study and TCGA groups, PCMT1 expression did not correlate with lymph node involvement and distant metastases but correlated with tumor stage. The results obtained in a larger TCGA group are consistent with those in our research group. Overexpression of PCMT1 was a prognostic marker of shorter survival in patients with TNBC. CONCLUSIONS: The overexpression of the PCMT1 protein in triple negative breast cancer significantly correlated with shorter overall survival. The confirmed association could be a potential prognostic biomarker for patients with TNBC.

High MAL2 expression predicts shorter survival in women with triple-negative breast cancer.

INTRODUCTION: Due to its lack of conventional surface receptors, triple-negative breast cancer (TNBC) is inherently resistant to most targeted therapies. MAL2 overexpression prompts endocytosis, conferring resistance to novel therapeutics. This study explores the role of MAL2 and PD-L1 in TNBC patients' prognosis. METHODS: We performed immunohistochemical analysis on 111 TNBC samples collected from 76 patients and evaluated the expression of MAL2 and PD-1. We expanded the study by including The Cancer Genome Atlas (TCGA) cohort. RESULTS: MAL2 expression did not correlate with stage, grade, tumor size, lymph node invasion, metastasis, and PD-1 expression. Patients with high MAL2 had significantly lower 5-year survival rates (71.33% vs. 89.59%, p = 0.0224). In the tissue microarray cohort (TMA), node invasions, size, recurrence, and low MAL2 (HR 0.29 [CI 95% 0.087-0.95]; p < 0.05) predicted longer patients' survival. In the TCGA cohort, patients with low MAL2 had significantly longer overall survival and disease-specific survival than patients with high MAL2. Older age and high MAL2 expression were the only independent predictors of shorter patient survival in the BRCA TCGA cohort. CONCLUSION: High MAL2 predicts unfavorable prognosis in triple-negative breast cancer, and its expression is independent of PD-1 levels and clinicopathological features of TNBC.

The prognostic role of p53 and its correlation with CDK9 in urothelial carcinoma.

PURPOSE: The mutation of p53 is considered a pivotal step in bladder cancer pathogenesis. Recently, distinct interactions between p53 and CDK9, a transcription regulator, have been described. In this work, we explored the prognostic role of p53 expression and evaluated its associations with CDK9 in urothelial carcinoma. MATERIALS AND METHODS: The research group consisted of 67 bladder cancer samples and 32 normal urothelial mucosa samples. All specimens were analyzed using ImageJ and the IHC profiler plugin. To validate the results, 406 cases from The Cancer Genome Atlas database were analyzed. RESULTS: P53 and CDK9 are overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High p53 expression was observed in metastatic tumors and tumors with high CDK9 expression (p < 0,05). High p53 expression was predictive for shorter survival in patients with non-muscle-invasive bladder cancer (HR = 0.107 [0.012-0.96]; p = 0.046) but did not correlate with prognosis in the muscle-invasive group. In high CDK9 cancers, high p53 expression correlated with the occurrence of high-grade and muscle-invasive tumors (p < 0.05). CONCLUSION: High expression of p53 correlates with unfavorable clinical features of bladder cancer. CDK9 is associated with the expression of p53, possibly through interactions with p53 inhibitors. Since the blockade of CDK9 in other malignancies reactivates wild-p53 activity, confirming the crosstalk between p53 and CDK9 in bladder cancer may be another step to explain the mechanism of tumor progression in its early stages.