Background/Objectives: Colorectal cancer (CRC) arises from the epithelial lining of the colon or rectum, often following a progression from benign adenomatous polyps to malignant carcinoma. Screening modalities such as colonoscopy, faecal immunochemical tests (FIT), and FIT-DNA are critical for early detection and prevention, but non-invasive methods lack sensitivity to polyps and early CRC. Chromosome conformations (CCs) are potent epigenetic regulators of gene expression. We have previously developed an epigenetic assay, EpiSwitch®®, that employs an algorithmic-based CCs analysis. Using EpiSwitch®®technology, we have shown the presence of cancer-specific CCs in peripheral blood mononuclear cells (PBMCs) and primary tumours of patients with melanoma and prostate cancer. EpiSwitch®®-based commercial tests are now available to diagnose prostate cancer with 94% accuracy (PSE test) and response to immune checkpoint inhibitors across 14 cancers with 85% accuracy (CiRT test). Methods/Results/Conclusions: Using blood samples collected fromn= 171 patients with CRC,n= 44 patients with colorectal polyps andn= 110 patients with a ‘clear’ colonoscopy we performed whole Genome DNA screening for CCs correlating to CRC diagnosis. Our findings suggest the presence of two eight-marker CC signatures (EpiSwitch®®NST) in whole blood that allow diagnosis of CRC and precancerous polyps, respectively. Independent validation cohort testing demonstrated high accuracy in identifying colorectal polyps and early versus late stages of CRC with an exceptionally high sensitivity of 79–90% and a high positive prediction value of 60–84%. Linking the top diagnostic CCs to nearby genes, we have built pathways maps that likely underline processes contributing to the pathology of polyp and CRC progression, including TGFβ, cMYC, Rho GTPase, ROS, TNFa/NFκB, and APC.
背景/目的：结直肠癌（CRC）起源于结肠或直肠的上皮组织，通常由良性腺瘤性息肉逐步发展为恶性癌变。结肠镜检查、粪便免疫化学检测（FIT）及FIT-DNA等筛查手段对早期发现和预防至关重要，但非侵入性方法对息肉及早期结直肠癌的检测敏感性不足。染色体构象（CCs）是基因表达的关键表观遗传调控因子。我们先前开发了一种基于算法分析的染色体构象表观遗传检测技术EpiSwitch®®。通过该技术，我们已在黑色素瘤和前列腺癌患者的外周血单核细胞（PBMCs）及原发肿瘤中证实了癌症特异性染色体构象的存在。目前基于EpiSwitch®®技术的商业化检测已能实现前列腺癌诊断（PSE检测）94%的准确率，以及对14种癌症的免疫检查点抑制剂反应预测（CiRT检测）85%的准确率。方法/结果/结论：通过收集171例结直肠癌患者、44例结直肠息肉患者及110例结肠镜检查“未见异常”患者的血液样本，我们进行了全基因组DNA筛查以分析与结直肠癌诊断相关的染色体构象。研究发现，全血中存在两组八标志物染色体构象特征谱（EpiSwitch®®NST），可分别用于结直肠癌及癌前息肉的诊断。独立验证队列测试显示，该技术对结直肠息肉及结直肠癌早晚期鉴别具有高准确性，其灵敏度达79–90%，阳性预测值达60–84%。通过将关键诊断性染色体构象与邻近基因关联，我们构建了可能揭示息肉及结直肠癌进展病理机制的通路图谱，涉及TGFβ、cMYC、Rho GTP酶、ROS、TNFα/NFκB及APC等通路。
肿瘤(癌症)患者之家