文章：

原发性结直肠肿瘤表现出与肝转移和腹膜转移相关的差异基因组表达谱

Primary Colorectal Tumor Displays Differential Genomic Expression Profiles Associated with Hepatic and Peritoneal Metastases

原文发布日期：4 September 2023

DOI: 10.3390/cancers15174418

类型: Article

开放获取: 是

英文摘要：

Background: Despite improvements in characterization of CRC heterogeneity, appropriate risk stratification tools are still lacking in clinical practice. This study aimed to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes. Methods: Primary tumor specimens obtained from CRC patients with either isolated LM (CRC-Liver) or PM (CRC-Peritoneum) were analyzed by transcriptomic mRNA sequencing, gene set enrichment analyses (GSEA) and immunohistochemistry. We further assessed the clinico-pathological associations and prognostic value of our signature in the COAD-TCGA independent cohort. Results: We identified a significantly different distribution of Consensus Molecular Subtypes between CRC-Liver and CRC-peritoneum groups. A transcriptomic signature based on 61 genes discriminated between liver and peritoneal metastatic routes. GSEA showed a higher expression of immune response and epithelial invasion pathways in CRC-Peritoneum samples and activation of proliferation and metabolic pathways in CRC-Liver samples. The biological relevance of RNA-Seq results was validated by the immunohistochemical expression of three significantly differentially expressed genes (ACE2, CLDN18andDUSP4) in our signature. In silico analysis of the COAD-TCGA showed that the CRC-Peritoneum signature was associated with negative prognostic factors and poor overall and disease-free survivals. Conclusions: CRC primary tumors spreading to the liver and peritoneum display significantly different transcriptomic profiles. The implementation of this signature in clinical practice could contribute to identify new therapeutic targets for stage IV CRC and to define individualized follow-up programs in stage II-III CRC.

摘要翻译： 

背景：尽管结直肠癌异质性表征研究已取得进展，但临床实践中仍缺乏合适的风险分层工具。本研究旨在阐明与不同转移途径相关的原发肿瘤转录组特征。方法：通过转录组mRNA测序、基因集富集分析和免疫组化技术，对来自仅发生肝转移或腹膜转移的结直肠癌患者的原发肿瘤标本进行分析。我们进一步在COAD-TCGA独立队列中评估了该特征的临床病理学关联及预后价值。结果：我们发现肝转移组与腹膜转移组在共识分子亚型分布上存在显著差异。基于61个基因构建的转录组特征可有效区分肝转移与腹膜转移途径。基因集富集分析显示，腹膜转移样本中免疫应答和上皮侵袭通路表达更高，而肝转移样本中增殖和代谢通路更为活跃。通过免疫组化验证了特征中三个显著差异表达基因的生物相关性。对COAD-TCGA数据库的计算机模拟分析表明，腹膜转移特征与不良预后因素及较差的总生存期和无病生存期相关。结论：发生肝转移与腹膜转移的结直肠癌原发肿瘤具有显著不同的转录组特征。该特征的临床应用有助于发现IV期结直肠癌的新治疗靶点，并为II-III期结直肠癌制定个体化随访方案。

原文链接：

Primary Colorectal Tumor Displays Differential Genomic Expression Profiles Associated with Hepatic and Peritoneal Metastases