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

总结 筛查仍然是结直肠癌（CRC）控制和预防的关键干预措施， 切除癌前病变可以防止发展为癌症。结肠镜检查，CRC的金标准 筛查，是一种侵入性和昂贵的程序，导致一般和低依从性， 筛查人群，包括低收入和早发性年轻患者。粪便筛查方法还 遵守率低。负担得起的微创方法是迫切需要解决的问题， 筛查率低，通过早期发现预防CRC。我们建议探索场的概念 在结直肠癌中的作用或同时发生结肠癌前息肉远端的细微变化， 一种创新的方式，为CRC开发一种新的筛查模式。肥大细胞（MC）是先天性免疫细胞 位于接近肠上皮和血管的稳态，其积累是一个 小鼠肠息肉病和侵袭性肠病变的基本特征。我们假设MC 在癌前病变时可能在结肠腔内斯劳，但在正常健康病例中不会脱落，因此 可以通过直肠擦拭与其他细胞一起接触。结合我们的双重专业知识， 成像和肥大细胞（MC）生物学，我们推测拭子收集的细胞可以在显微镜下分析 使用明视野显微镜和图像分析软件处理和染色MC后的载玻片。我们 使用两种CRC临床前模型的初步结果，遗传ApcMin/+小鼠模型和 氧化偶氮甲烷/葡聚糖硫酸钠诱导的结肠炎导致CRC，表明拭子中存在MC。 携带息肉，但不存在于健康的无息肉、无发炎的息肉、无癌症或野生型小鼠中。确保 标准化样本分析，我们建议开发一种用于拭子MC检测的计算成像方法 通过整合MC限制的形态测量描述符。将进行进一步的生物学和技术验证 执行。如果得到证实，我们的工作假设将在人类试点研究中进行测试。

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.