Department of Basic Science, Division of Biochemistry, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Ann Surg Oncol. 2023 Jun;30(6):3833-3844. doi: 10.1245/s10434-023-13219-7. Epub 2023 Mar 2.
Liquid biopsies have become an integral part of cancer management as minimally invasive options to detect molecular and genetic changes. However, current options show poor sensitivity in peritoneal carcinomatosis (PC). Novel exosome-based liquid biopsies may provide critical information on these challenging tumors. In this initial feasibility analysis, we identified an exosome gene signature of 445 genes (ExoSig445) from colon cancer patients, including those with PC, that is distinct from healthy controls.
Plasma exosomes from 42 patients with metastatic and non-metastatic colon cancer and 10 healthy controls were isolated and verified. RNAseq analysis of exosomal RNA was performed and differentially expressed genes (DEGs) were identified by the DESeq2 algorithm. The ability of RNA transcripts to discriminate control and cancer cases was assessed by principal component analysis (PCA) and Bayesian compound covariate predictor classification. An exosomal gene signature was compared with tumor expression profiles of The Cancer Genome Atlas.
Unsupervised PCA using exosomal genes with greatest expression variance showed stark separation between controls and patient samples. Using separate training and test sets, gene classifiers were constructed capable of discriminating control and patient samples with 100% accuracy. Using a stringent statistical threshold, 445 DEGs fully delineated control from cancer samples. Furthermore, 58 of these exosomal DEGs were found to be overexpressed in colon tumors.
Plasma exosomal RNAs can robustly discriminate colon cancer patients, including patients with PC, from healthy controls. ExoSig445 can potentially be developed as a highly sensitive liquid biopsy test in colon cancer.
液体活检已成为癌症管理的重要组成部分，是检测分子和遗传变化的微创选择。然而，目前的选择在腹膜癌病（PC）中显示出较差的敏感性。新型基于外泌体的液体活检可能为这些具有挑战性的肿瘤提供关键信息。在这项初步可行性分析中，我们从结肠癌患者（包括患有 PC 的患者）中鉴定了一个由 445 个基因组成的外泌体基因特征（ExoSig445），与健康对照者不同。
从 42 名转移性和非转移性结肠癌患者和 10 名健康对照者的血浆外泌体中分离并验证。对外泌体 RNA 进行 RNAseq 分析，并通过 DESeq2 算法鉴定差异表达基因（DEG）。通过主成分分析（PCA）和贝叶斯复合协变量预测分类评估 RNA 转录物区分对照和癌症病例的能力。将外泌体基因特征与癌症基因组图谱中的肿瘤表达谱进行比较。
使用具有最大表达方差的外泌体基因进行无监督 PCA 显示出对照和患者样本之间的明显分离。使用单独的训练和测试集，构建了能够以 100%的准确率区分对照和患者样本的基因分类器。使用严格的统计阈值，445 个 DEG 完全将对照与癌症样本区分开来。此外，在结肠癌中发现其中 58 个外泌体 DEG 过表达。
血浆外泌体 RNA 可以可靠地区分结肠癌患者，包括患有 PC 的患者，与健康对照者。ExoSig445 可能被开发为结肠癌的高敏感液体活检测试。
