PO.CL01.17 · 临床研究
晚期结直肠癌中骨骼肌基因表达和恶病质的预后影响
Prognostic impacts of skeletal muscle gene expression and cachexia in advanced colorectal cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：癌症恶病质是一种复杂的代谢综合征，以严重肌肉丢失、身体功能下降和治疗反应减弱为特征。尽管其具有临床影响，转移性结直肠癌来源的晚期腹膜癌病（pmCRC）患者中恶病质的转录图谱仍未充分明确。我们的研究旨在表征pmCRC患者伴恶病质的骨骼肌改变。
方法：从17例签署IRB组织采集知情同意并接受细胞减灭术联合腹腔热灌注化疗（CRS/HIPEC）的pmCRC患者中获取肌肉活检，根据骨骼肌指数（SMI cm2/m2）分为肌肉减少型（n=7）或非肌肉减少型（n=11）。活检样本送RNA测序，使用edgeR软件中的统计算法进行差异表达分析。我们比较两个队列并选择表达显著增加或减少的差异表达基因（DEG）（变化>2倍且p值<0.05）。富集分析识别了与恶病质病理生理相关的基因集和通路。最后，进行生存分析以评估所识别DEG在预测患者结局中的预后价值。
结果：我们的分析揭示了231个DEG，包括肌肉减少组中75个上调和156个下调基因。富集分析显示了多条参与免疫细胞信号传导的通路。总生存分析揭示七个DEG与生存结局相关，其中六个在结直肠癌或其他癌症类型（包括胰腺腺癌、肝细胞癌、肾细胞癌和口腔鳞状细胞癌）中具有相关预后价值。在我们的患者队列中，一个DEG的高表达和其余预后基因的低表达与不良生存相关。
结论：我们的研究突显了pmCRC中癌症诱导恶病质的分子特征以及若干潜在的诊断和预后生物标志物。
查看英文原文 English abstract
Background: Cancer cachexia is a complex metabolic syndrome characterized by severe muscle loss, reduced physical function, and diminished therapeutic response. Despite its clinical impacts, the transcriptional landscape of cachexia in patients with advanced peritoneal carcinomatosis from metastatic colorectal cancer (pmCRC) remains poorly defined. Our study aims to characterize alterations in skeletal muscle with associated cachexia in pmCRC patients.
Methods: Muscle biopsies were obtained from 17 pmCRC patients consented for IRB tissue collection and undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), classified as myopenic (n=7) or non-myopenic (n=11) based on skeletal muscle index (SMI cm2/m2). Biopsies were sent for RNA sequencing and differential expression analysis was performed utilizing statistical algorithms within edgeR software. We compared the two cohorts and selected differentially expressed genes (DEGs) with significantly increased or decreased expression (>2-fold change and p-value <0.05). Enrichment analysis identified gene sets and pathways relevant to cachexia pathophysiology. Last, survival analysis was performed to assess the prognostic value of identified DEGs in predicting patient outcomes.
Results: Our analysis revealed 231 genes DEGs, including 75 upregulated and 156 downregulated genes in the myopenic group. Enrichment analysis exhibited several pathways involved in immune cell signaling. Overall survival analysis revealed associations with survival outcomes for seven DEGs-six of which have associated prognostic value in colorectal cancer or other cancer variants including pancreatic adenocarcinoma, hepatocellular carcinoma, renal cell carcinoma and oral squamous cell carcinoma. High expression of one DEG and low expression of the remaining prognostic genes were linked with poor survival in our patient cohort.
Conclusions: Our study highlights molecular features of cancer-induced cachexia in pmCRC and several potential diagnostic and prognostic biomarkers.
利益披露 Disclosure
V. L. Bandy, None.