Background: Endometrial cancer is strongly associated with obesity, and tumors often harbor mutations in major cancer signaling pathways. To inform the integration of body composition into targeted therapy paradigms, this hypothesis-generating study explores the association between muscle mass, body fat, and tumor proteomics.Methods: We analyzed data from 113 patients in The Cancer Genome Atlas (TCGA) and Cancer Proteomic Tumor Analysis Consortium (CPTAC) cohorts and their corresponding abdominal CT scans. Among these patients, tumor proteomics data were available for 45 patients, and 133 proteins were analyzed. Adiposity and muscle components were assessed at the L3 vertebral level on the CT scans. Patients were stratified into tertiles of muscle and fat mass and categorized into three groups: high muscle/low adiposity, high muscle/high adiposity, and low muscle/all adiposities. Linear and Cox regression models were adjusted for study cohort, stage, histology type, age, race, and ethnicity.Results: Compared with the high-muscle/low-adiposity group, both the high-muscle/high-adiposity (HR = 4.3, 95% CI = 1.0–29.0) and low-muscle (HR = 4.4, 95% CI = 1.3–14.9) groups experienced higher mortality. Low muscle was associated with higher expression of phospho-4EBP1(T37 and S65), phospho-GYS(S641) and phospho-MAPK(T202/Y204) but lower expression of ARID1A, CHK2, SYK, LCK, EEF2, CYCLIN B1, and FOXO3A. High muscle/high adiposity was associated with higher expression of phospho-4EBP1 (T37), phospho-GYS (S641), CHK1, PEA15, SMAD3, BAX, DJ1, GYS, PKM2, COMPLEX II Subunit 30, and phospho-P70S6K (T389) but with lower expression of CHK2, CRAF, MSH6, TUBERIN, PR, ERK2, beta-CATENIN, AKT, and S6.Conclusions: These findings demonstrate an association between body composition and proteins involved in key cancer signaling pathways, notably the PI3K/AKT/MTOR, MAPK/ERK, cell cycle regulation, DNA damage response, and mismatch repair pathways. These findings warrant further validation and assessment in relation to prognosis and outcomes in these patients.
背景：子宫内膜癌与肥胖密切相关，且肿瘤常携带主要癌症信号通路突变。为探索将身体成分纳入靶向治疗模式的可行性，这项假设生成性研究探讨了肌肉量、体脂与肿瘤蛋白质组学之间的关联。 方法：我们分析了来自癌症基因组图谱（TCGA）和癌症蛋白质组肿瘤分析联盟（CPTAC）队列的113例患者数据及其对应的腹部CT扫描。其中45例患者可获得肿瘤蛋白质组学数据，共分析了133种蛋白质。通过CT扫描在L3椎体水平评估脂肪和肌肉成分。将患者按肌肉量和脂肪量分为三等分，并归类为三组：高肌肉/低脂肪组、高肌肉/高脂肪组和低肌肉/全脂肪组。线性回归和Cox回归模型针对研究队列、分期、组织学类型、年龄、种族和民族进行了调整。 结果：与高肌肉/低脂肪组相比，高肌肉/高脂肪组（HR = 4.3，95% CI = 1.0–29.0）和低肌肉组（HR = 4.4，95% CI = 1.3–14.9）的死亡率均较高。低肌肉与磷酸化4EBP1（T37和S65）、磷酸化GYS（S641）和磷酸化MAPK（T202/Y204）的高表达相关，但与ARID1A、CHK2、SYK、LCK、EEF2、CYCLIN B1和FOXO3A的低表达相关。高肌肉/高脂肪与磷酸化4EBP1（T37）、磷酸化GYS（S641）、CHK1、PEA15、SMAD3、BAX、DJ1、GYS、PKM2、复合物II亚基30和磷酸化P70S6K（T389）的高表达相关，但与CHK2、CRAF、MSH6、TUBERIN、PR、ERK2、β-连环蛋白、AKT和S6的低表达相关。 结论：这些发现表明身体成分与参与关键癌症信号通路的蛋白质之间存在关联，特别是PI3K/AKT/MTOR、MAPK/ERK、细胞周期调控、DNA损伤反应和错配修复通路。这些发现值得进一步验证，并评估其与患者预后和结局的关系。
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