Reduced cytoplasmic expression of MAGE-A2 predicts tumor aggressiveness and survival: an immunohistochemical analysis.

BACKGROUND: Melanoma antigen gene A2 (MAGE-A2) is one of the most cancer-testis antigens overexpressed in various types of cancers. Silencing the MAGE-A2 expression inhibited the proliferation of prostate cancer (PCa) cells and increased the chemosensitivity. However, the expression pattern of MAGE-A2 in PCa tissue samples and its prognostic and therapeutic values for PCa patients is still unclear. METHODS: In this study, for the first time, the staining pattern and clinical significance of MAGE-A2 were evaluated in 166 paraffin-embedded prostate tissues, including 148 cases of PCa and 18 cases of high-grade prostatic intraepithelial neoplasia (HPIN), by immunohistochemical analysis. RESULTS: The simultaneous expression of both nuclear and cytoplasmic patterns of MAGE-A2 with different staining intensities was observed among studied cases. Increased expression of MAGE-A2 was significantly found in PCa tissues compared to HPIN cases (P < 0.0001). Among PCa samples, the strong staining intensity of nuclear expression was predominantly observed in comparison with cytoplasmic expression in PCa tissues (P < 0.0001). A significant and inverse correlation was found between the cytoplasmic expression of MAGE-A2 and increased Gleason score (P = 0.002). Increased cytoplasmic expression of MAGE-A2 was associated with longer biochemical recurrence-free survival (BCR-FS) and disease-free survival (DFS) of patients (P = 0.002, P = 0.001, respectively). In multivariate analysis, Gleason score and cytoplasmic expression of MAGE-A2 were independent predictors of the BCR-FS (P = 0.014; P = 0.028, respectively). CONCLUSIONS: Taken together, cytoplasmic expression of MAGE-A2 was inversely proportional to the malignant grade and duration of recurrence of the disease in patients with PCa.

Implications the Role of miR-155 in the Pathogenesis of Autoimmune Diseases.

MicroRNAs (miRNAs) are small noncoding conserved RNAs containing 19 to 24 nucleotides that are regulators of post-translational modifications and are involved in the majority of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development. Autoimmune diseases are characterized by immune system dysregulation, which ultimately leads to destructive responses to self-antigens. A large body of literature suggests that autoimmune diseases and immune dysregulation are associated with different miRNA expression changes in the target cells and tissues of adaptive or innate immunity. miR-155 is identified as a critical modulator of immune responses. Recently conducted studies on the expression profile of miR-155 suggest that the altered expression and function of miR-155 can mediate vulnerability to autoimmune diseases and cause significant dysfunction of the immune system.

Nuclear overexpression levels of MAGE-A3 predict poor prognosis in patients with prostate cancer.

Melanoma antigen gene A3 (MAGE-A3) is one of the most immunogenic cancer testis antigens and is common in various types of cancers. In this study, for the first time, we performed immunohistochemical analysis to evaluate the expression of MAGE-A3 in 153 prostate tissue samples including prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostatic intraepithelial neoplasia (HPIN). Increased both nuclear and cytoplasmic expression of MAGE-A3 was significantly found in PCa tissues compared with both HPIN and BPH tissues (nuclear expression at p = 0.011, and cytoplasmic expression at p = 0.034; for both comparisons p < 0.0001, respectively). A significant correlation was observed between higher nuclear and cytoplasmic expressions of MAGE-A3 with Gleason score (p < 0.0001 and 0.006, respectively). Increased expression of MAGE-A3 was associated with shorter biochemical recurrence-free survival (BCR-FS) and disease-free survival (DFS) of patients (p = 0.042 and = 0.0001, respectively). In multivariate analysis, nuclear expression of MAGE-A3 and Gleason score (≤7 vs >7) was independent predictors of the DFS (both; p = 0.019). Nuclear expression of MAGE-A3 was also significantly related to BCR-FS (p = 0.015). MAGE-A3 can be considered as a predictor for poor prognosis and an option for vaccine immunotherapy in patients with PCa.