PO.PS01.09 · 人群科学
子宫内膜癌患者的CT评估身体成分与肿瘤免疫学特征
CT-assessed body composition and tumor immunologic characteristics in patients with endometrial cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：身体成分的变化，特别是脂肪和肌肉量，可能影响组织免疫浸润。然而，这些成分与子宫内膜癌肿瘤免疫微环境之间的关系仍未明确界定。我们旨在探讨CT评估的身体成分是否与子宫内膜癌的肿瘤免疫细胞浸润相关。
方法：我们分析了来自癌症基因组图谱（TCGA）和临床蛋白质组肿瘤分析联盟（CPTAC）的63例子宫内膜癌患者，这些患者在L3椎体水平有治疗前CT身体成分测量数据以及基于bulk RNA-seq的免疫解卷积数据。约75%的患者为子宫内膜样腺癌。以绝对模式估计22个CIBERSORTx衍生亚群的免疫细胞丰度；排除零值≥75%的亚群，保留14种免疫细胞类型加上CIBERSORT总免疫评分用于分析。评估了八项CT衍生的身体成分指标，包括内脏脂肪组织（VAT）、皮下脂肪组织（SAT）、肌间脂肪组织（IMAT）、骨骼肌面积以及相应的基于Hounsfield单位（HU）的密度测量。线性回归模型评估了身体成分指标与经log1p转换的免疫丰度之间的关联。分析采用单变量和多变量模型，并对年龄和队列进行校正。使用Benjamini-Hochberg错误发现率（FDR）对p值进行多重检验校正。
结果：免疫细胞丰度普遍较低（大多数亚群中位数<0.10）。在单变量模型中，较高的VAT名义上与较低的总免疫评分以及若干固有免疫亚群丰度降低相关，包括NK细胞（静息和活化）和巨噬细胞（M0/M1）（所有p<0.05）。相比之下，若干基于HU的密度指标，包括SATHU和IMATHU，显示与CD8 T细胞呈名义上的正相关。然而，经FDR校正后无关联仍具有统计学意义（所有FDR ≥0.32）。校正年龄和队列的多变量模型产生了相似的模式。
结论：在这个探索性队列中，CT衍生的身体成分指标与免疫细胞浸润显示出异质性关联。内脏脂肪与固有免疫浸润显示出潜在的负相关，而较高的皮下脂肪组织与CD8 T细胞显示出潜在的正相关。这些异质性的固有和适应性免疫模式提示身体成分与免疫浸润的关系可能存在差异，值得在更大队列中进一步研究。
查看英文原文 English abstract
Background: Variations in the body composition, specifically fat and muscle mass, may influence tissue immune infiltration. However, the relationships between these components and the tumor immune microenvironment in endometrial cancer remain poorly defined. We aimed to investigate whether CT-assessed body composition is associated with tumor immune cell infiltration in endometrial cancer.
Methods: We analyzed 63 patients with endometrial cancer from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) who had pre-treatment CT body composition measurements at the L3 vertebral level and bulk RNA-seq-based immune deconvolution. Approximately 75% of these patients had endometrioid adenocarcinoma. Immune cell abundances for 22 CIBERSORTx-derived subsets were estimated in absolute mode; subsets with ≥75% zero values were excluded, leaving 14 immune cell types plus the CIBERSORT total immune score for analysis. Eight CT-derived body composition metrics were evaluated, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), skeletal muscle areas, and corresponding Hounsfield unit (HU)-based density measures. Linear regression models assessed associations between body composition metrics and log1p-transformed immune abundances. Analyses were conducted using univariable and multivariable models adjusting for age and cohort. P-values were corrected for multiple testing using the Benjamini-Hochberg false discovery rate (FDR).
Results: Immune cell abundances were generally low (median<0.10 for most subsets). In univariable models, higher VAT was nominally associated with lower total immune score and reduced abundances of several innate immune subsets, including NK-cell (resting and activated), and macrophage (M0/M1) (all p<0.05). In contrast, several HU-based density metrics, including SATHU and IMATHU, showed nominal positive associations with CD8 T cells. However, no associations remained statistically significant after FDR correction (all FDR ≥0.32). Multivariable models adjusting for age and cohort yielded similar patterns.
Conclusion: In this exploratory cohort, CT-derived body composition metrics showed heterogeneous associations with immune cell infiltration. Visceral adiposity showed potential inverse associations with innate immune infiltration, whereas higher subcutaneous adipose tissue showed potential positive associations with CD8 T-cells. These heterogeneous innate and adaptive immune patterns suggest potential differences in how body composition relates to immune infiltration, warranting further investigation in larger cohorts.
利益披露 Disclosure
Y. Zhang, None..
C. M. Mahenge, None..
J. Krull, None..
R. T. Akasheh, None..
L. Chambers, None..
X. Nguyen, None..
T. D. Cheng, None.