A Comprehensive Pan-Cancer Analysis of the Mitochondrial Uncoupling Protein UCP2, with a Focus on Sex and Gender-Related Aspects

• Published in: Cellular physiology and biochemistry Vol. 58; no. 5; p. 630
• Main Authors: Sadeghi, Soha, Checchetto, Vanessa, Varanita, Tatiana
• Format: Journal Article
• Language: English
• Published: Germany 27.10.2024
• Subjects: Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Female; Humans; Male; Microsatellite Instability; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Prognosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Sex Factors; Testicular Neoplasms - genetics; Testicular Neoplasms - metabolism; Testicular Neoplasms - pathology; Uncoupling Protein 2 - genetics; Uncoupling Protein 2 - metabolism; UCP2 ; Pan-cancer ; Gender-related cancers ; Expression ; Prognosis
• DOI: 10.33594/000000735
• ISSN: 1421-9778

Mitochondrial uncoupling protein 2 (UCP2) plays a crucial role in regulating oxidative stress and cellular metabolism, positioning it as an important subject in oncological research. The involvement of UCP2 in cancer is complex and context-dependent, suggesting it as a potential therapeutic target. In this study, we aimed to perform a comprehensive pan-cancer analysis of UCP2, with a particular focus on gender-related malignancies such as breast (BRCA), prostate (PRAD), ovarian (OV), and testicular tumors (TGCT). We analyzed expression in The Cancer Genome Atlas (TCGA), examining correlations with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), immune cell infiltration, immune checkpoint genes, genes involved in steroidogenesis, sex hormone receptor genes, and drug sensitivity. Significant variability in UCP2 expression was observed across cancer types. levels were elevated in BRCA and OV but reduced in PRAD and TGCT. High expression was associated with a better prognosis in OV and poorer overall survival in PRAD. Furthermore, correlated with TMB and MSI in OV, TGCT, and BRCA. expression was also linked to immune cell infiltration, immune checkpoint genes, steroidogenic genes, and sex hormone receptor genes, with variable effects depending on cancer type and gender. Additionally, also demonstrated sensitivity to specific anticancer drugs. Our findings highlight the interplay between UCP2, immune and hormonal pathways, and drug response and reveal potential opportunities for new therapeutic combinations, especially in gender-related cancers.