Development of a noninvasive, rapid and affordable method for early detection of colorectal cancer

摘要 筛查仍然是结直肠癌(CRC)控制和预防的关键干预措施，因为检测和 切除癌前病变可以防止进展为癌症。结肠镜检查--结直肠癌的黄金标准 筛查是一种侵入性且费用高昂的程序，导致一般人群和低收入人群的依从性较低。 筛查人群，包括低收入和早发年轻患者。粪便筛查方法也包括 合规率较低。负担得起的微创方法迫切需要解决 筛查率低，通过早期发现预防结直肠癌。我们建议探索场的概念 结直肠癌的影响或同时发生结肠癌前息肉远端细微改变 一种创新的方式，开发一种新的结直肠癌筛查模式。肥大细胞(MC)是先天免疫细胞 位于接近肠上皮和血管的动态平衡，其积累是一种 小鼠肠道息肉病和侵袭性肠道病变的基本特征。我们假设MC 可能在癌前病变时在结肠腔内脱落，但在正常健康病例中不会，因此 可与其他细胞一起通过直肠拭子获取。结合我们在量化方面的双重专业知识 成像和肥大细胞(MC)生物学，我们推测拭子采集的细胞可以在显微镜下分析。 采用明视场显微镜和图像分析软件对切片进行处理和MC染色。我们的 使用两种结直肠癌临床前模型的初步结果，即遗传ApcMin/+小鼠模型和 偶氮甲烷/葡聚糖硫酸钠诱导的结肠炎导致结直肠癌，提示拭子MC在 携带息肉，但不在健康的无息肉、发炎的息肉、癌症或野生型小鼠中携带。为了确保 标准化样本分析，我们建议开发一种用于棉签MC检测的计算成像方法 通过集成MC-受限的形态描述符。进一步的生物和技术验证将是 已执行。如果得到证实，我们的工作假设将在人体先导研究中得到验证。

SUMMARY Screening remains the key intervention for colorectal cancer (CRC) control and prevention as detection and removal of premalignant lesions can prevent progression to cancer. Colonoscopy, the gold standard for CRC screening, is an invasive and costly procedure resulting in low compliance in both the general and the under- screened populations, including low-income and early-onset young patients. Feces-screening methods also suffer low compliance rates. Affordable and minimally invasive approaches are urgently warranted to address low screening rates and prevent CRC through early detection. We are proposing to explore the concept of field effect in CRC or simultaneous occurrence of subtle alterations distal from precancerous polyps in the colon, in an innovative way, to develop a new screening modality for CRC. Mast cells (MC) are innate immune cells located close to the intestinal epithelium and blood vessels at homeostasis, whose accumulation is an essential feature of intestinal polyposis in mice and of invasive intestinal lesions. We hypothesized that MC might slough off in the colonic lumen upon precancerous transformation, but not in normal healthy cases, thus being accessible by rectal swabbing, together with other cells. Combining our dual expertise in quantitative imaging and mast cell (MC) biology, we surmise that swab-collected cells might be analyzed on microscopy slides after processing and staining for MC using bright-field microscopy and image analysis software. Our preliminary results using two preclinical models of CRC, the genetic ApcMin/+ mouse model and the azoxymethane/dextran sulfate sodium-induced colitis leading to CRC, indicate the presence of swab MC in polyp carrying but not in healthy polyp-free, inflamed polyp-free, cancer-free or wild type mice. To ensure standardized sample analysis, we propose to develop a computational imaging method for swab MC detection by integrating MC-restricted morphometric descriptors. Further biological and technical validations will be performed. If confirm, our working hypothesis will be tested in a human pilot study.