Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine.
乳腺癌是一种异质性疾病，不同分子亚型（MS）表现出不同的预后和治疗反应。本研究从IPO-Porto肿瘤生物样本库获取了62例按分子亚型分层的乳腺癌样本，通过免疫组织化学方法检测了糖酵解和糖异生调控酶的表达。数据分析根据分子亚型、体重指数（BMI）以及分子亚型联合BMI（mBMI）进行分层。研究发现，当按分子亚型和mBMI分层时，丙酮酸羧化酶（PC）、磷酸烯醇式丙酮酸羧激酶（PCK）和果糖-1,6-二磷酸酶（FBP）在肿瘤细胞中的表达存在显著差异。这些酶的表达还与激素受体和HER2状态存在统计学相关性，并与病理分期和组织学分级相关。肥胖倾向于减弱这些差异，尤其是在PC表达方面，尽管这些差异不受肿瘤微环境中脂肪细胞沉积或炎症浸润的影响。然而，PCK和FBP的表达也受到糖尿病、高血压和血脂异常等肥胖相关疾病的影响。综上所述，这些发现揭示了乳腺癌作为不同组织学类型具有独特的代谢特征，这些特征受到肥胖及肥胖相关疾病的影响。尽管这些酶差异表达的生物学作用尚不明确，但本研究强调了将糖异生调控酶的表达识别作为个体化医疗工具的必要性。
肿瘤(癌症)患者之家