BACKGROUND & AIMS:
:Male breast cancer (MBC) is a rare hormone-driven disease often associated with obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR regulates the oncogenic Hippo transducers TAZ/YAP whose expression was previously associated with shorter survival in MBC. 225 MBC samples were immunostained for HMG-CoAR and 124 were considered eligible for exploring its relationship with hormone receptors (ER, PgR, AR), Hippo transducers and survival outcomes. HMG-CoAR was positively associated with the expression of hormone receptors (ER, PgR, AR) and Hippo transducers. Overall survival was longer in patients with HMG-CoAR-positive tumors compared with their negative counterparts (p = 0.031). Five- and 10-year survival outcomes were better in patients whose tumors expressed HMG-CoAR (p = 0.044 and p = 0.043). Uni- and multivariate analyses for 10-year survival suggested that HMG-CoAR expression is a protective factor (HR 0.50, 95% CI: 0.25-0.99, p = 0.048 and HR 0.53, 95% CI: 0.26-1.07, p = 0.078). Results were confirmed in a sensitivity analysis by excluding uncommon histotypes (multivariate Cox: HR 0.45, 95% CI: 0.21-0.97, p = 0.043). A positive relationship emerged between HMG-CoAR, hormone receptors and TAZ/YAP, suggesting a connection between the mevalonate pathway, the hormonal milieu and Hippo in MBC. Moreover, HMG-CoAR expression may be a favorable prognostic indicator.
背景与目标:
男性乳腺癌 (MBC) 是一种罕见的激素驱动疾病,通常与肥胖相关。HMG-CoAR是甲羟戊酸途径的中心酶,甲羟戊酸途径是一种产生胆固醇和类固醇激素的分子途径。HMG-CoAR调节致癌Hippo换能器TAZ/YAP,其表达先前与MBC的较短生存期相关。225 MBC样品对HMG-CoAR进行免疫染色,124被认为有资格探索其与激素受体 (ER,PgR,AR),Hippo换能器和生存结果的关系。HMG-CoAR与激素受体 (ER,PgR,AR) 和Hippo换能器的表达呈正相关。与阴性患者相比,HMG-CoAR阳性患者的总生存期更长 (p = 0.031)。肿瘤表达HMG-CoAR的患者 (p = 0.044,p = 0.043) 5年和10年的生存结局较好。10年生存率的单因素和多因素分析表明,HMG-CoAR表达是一种保护因子 (HR 0.50,95% ci ci: 0.25-0.99,p = 0.048和HR 0.53,95% CI: 0.26-1.07,p = 0.078)。通过排除不常见的组织类型 (多变量Cox: HR 0.45,95% CI: 0.21-0.97,p = 0.043),在敏感性分析中证实了结果。HMG-CoAR,激素受体和TAZ/YAP之间出现正相关关系,表明MBC中的甲羟戊酸途径,激素环境和河马之间存在联系。此外,HMG-CoAR表达可能是有利的预后指标。