Stratified Medicine Graduate Training Programme in Systems Medicine and Spectroscopic Profiling

结直肠癌（CRC）是第三大常见癌症类型，2018年全球记录了超过100万例病例。与CRC相关的高死亡率主要是疾病预后和诊断不良的结果。尽管包括活检和结肠镜检查的组织病理学分析在内的强大诊断工具有助于改善疾病预后，但使用这些方法无法提供有关肿瘤分期和疾病进展的信息。因此，非常需要开发一种更敏感和非侵入性的工具，可以在疾病的早期发作期间检测具有诊断和预后重要性的标志物。对这些标记物的需要在确定目前在临床中实施的化学治疗药物的效率方面也是至关重要的。近年来进行的研究旨在描述肠道微生物组在健康和疾病中的作用。强有力的证据表明，细菌生态失调可能导致许多代谢紊乱以及癌症的发展。因此，在疾病状态下特异性释放的代谢物可用作CRC的潜在标志物。目前实施的筛查工具使用粘膜和粪便样本。与样本收集相关的限制分别包括侵入性和患者卫生。因此，该项目旨在解决非侵入性血液检测的开发，筛查肠道微生物组功能，是否可以作为CRC发展以及药物效率的预后和诊断工具。为此，将采用包括GC-MS和LC-MS在内的分析技术来检测CRC患者血液样本中的循环标志物。这些基础研究不仅有助于开发新的CRC预后和诊断工具，还将为肠道微生物组与CRC相关的机制提供见解。这可以在治疗上用于改变肠道微生物群组成，以提高化疗效率和/或降低细胞毒性。

Colorectal cancer (CRC) is the third most common type of cancer with more than 1 million cases recorded in 2018 worldwide. The high mortality rates associated with CRC are mainly the result of poor disease prognosis and diagnosis. Although robust diagnostic tools including histopathological analysis of biopsies and coloscopies, have contributed to the improvement of disease prognosis, information regarding tumour stage and disease progression cannot be provided using these methods. Hence, there is a great need to develop a more sensitive and non-invasive tool that can detect markers of diagnostic and prognostic importance during the early onset of the disease. The need of such markers is also crucial in determining the efficiency of chemotherapeutic drugs that are currently implemented in clinic. Studies conducted in recent years aimed to delineate the role of gut microbiome in health and disease. Strong evidence suggests that bacteria dysbiosis can lead to the development of numerous metabolic disorders as well as cancer. Therefore, metabolites released specifically at the disease state can be used as potential markers of CRC. Currently implemented screening tools use mucosal and faecal samples. Limitations associated with sample collection include invasiveness and patients' hygiene respectively. Therefore, this project aims to address whether the development of a non-invasive blood test, screening the gut microbiome function, can act as a prognostic and diagnostic tool for CRC development as well as for drug efficiency. To this end, analytical techniques including GC-MS and LC-MS, will be employed to detect circulating markers in blood samples derived from CRC patients. Such fundamental research will not only aid in the development of a new prognostic and diagnostic tool for CRC but will also provide insights on the mechanisms associating gut microbiome with CRC. This could be exploited therapeutically to modify gut microbiota composition to both improve chemotherapy efficiency and/or reduce cytotoxicity.