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

IF 2.5 Q3 CELL BIOLOGY
Soha Sadeghi, Vanessa Checchetto, Tatiana Varanita
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引用次数: 0

Abstract

Background/aims: 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).

Methods: We analyzed UCP2 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.

Results: Significant variability in UCP2 expression was observed across cancer types. UCP2 levels were elevated in BRCA and OV but reduced in PRAD and TGCT. High UCP2 expression was associated with a better prognosis in OV and poorer overall survival in PRAD. Furthermore, UCP2 correlated with TMB and MSI in OV, TGCT, and BRCA. UCP2 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, UCP2 also demonstrated sensitivity to specific anticancer drugs.

Conclusion: 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.

线粒体解偶联蛋白 UCP2 的泛癌症综合分析,重点关注与性别相关的方面。
背景/目的:线粒体解偶联蛋白 2(UCP2)在调节氧化应激和细胞新陈代谢方面发挥着至关重要的作用,因此成为肿瘤学研究的一个重要课题。UCP2 在癌症中的参与是复杂的,且与环境有关,这表明它是一个潜在的治疗靶点。在本研究中,我们旨在对 UCP2 进行全面的泛癌症分析,尤其关注与性别相关的恶性肿瘤,如乳腺癌(BRCA)、前列腺癌(PRAD)、卵巢癌(OV)和睾丸癌(TGCT):我们分析了癌症基因组图谱(TCGA)中 UCP2 的表达,研究了其与预后、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、免疫细胞浸润、免疫检查点基因、参与类固醇生成的基因、性激素受体基因和药物敏感性的相关性:结果:不同癌症类型的 UCP2 表达存在显著差异。在 BRCA 和 OV 中 UCP2 水平升高,而在 PRAD 和 TGCT 中则降低。UCP2 的高表达与 OV 的较好预后和 PRAD 的较差总生存率相关。此外,UCP2 与 OV、TGCT 和 BRCA 中的 TMB 和 MSI 相关。UCP2 的表达还与免疫细胞浸润、免疫检查点基因、类固醇生成基因和性激素受体基因有关,其影响因癌症类型和性别而异。此外,UCP2 还表现出对特定抗癌药物的敏感性:我们的研究结果突显了 UCP2、免疫和激素通路与药物反应之间的相互作用,并揭示了新疗法组合的潜在机会,尤其是在与性别相关的癌症中。
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来源期刊
CiteScore
5.80
自引率
0.00%
发文量
86
审稿时长
1 months
期刊介绍: Cellular Physiology and Biochemistry is a multidisciplinary scientific forum dedicated to advancing the frontiers of basic cellular research. It addresses scientists from both the physiological and biochemical disciplines as well as related fields such as genetics, molecular biology, pathophysiology, pathobiochemistry and cellular toxicology & pharmacology. Original papers and reviews on the mechanisms of intracellular transmission, cellular metabolism, cell growth, differentiation and death, ion channels and carriers, and the maintenance, regulation and disturbances of cell volume are presented. Appearing monthly under peer review, Cellular Physiology and Biochemistry takes an active role in the concerted international effort to unravel the mechanisms of cellular function.
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