Yusof Hazwani Mohd, Ab-Rahim Sharaniza, Wan Ngah Wan Zurinah, Nathan Sheila, A Jamal A Rahman, Mazlan Musalmah
Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA, Campus Sungai Buloh, 47000 Sungai Buloh, Selangor, Malaysia.
Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Batu 9 Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia.
Bioimpacts. 2021;11(2):147-156. doi: 10.34172/bi.2021.22. Epub 2020 Jun 10.
Metabolomic studies on various colorectal cancer (CRC) cell lines have improved our understanding of the biochemical events underlying the disease. However, the metabolic profile dynamics associated with different stages of CRC progression is still lacking. Such information can provide further insights into the pathophysiology and progression of the disease that will prove useful in identifying specific targets for drug designing and therapeutics. Thus, our study aims to characterize the metabolite profiles in the established cell lines corresponding to different stages of CRC. Metabolite profiling of normal colon cell lines (CCD 841 CoN) and CRC cell lines corresponding to different stages, i.e., SW 1116 (stage A), HT 29 and SW 480 (stage B), HCT 15 and DLD-1 (stage C), and HCT 116 (stage D), was carried out using liquid chromatography-mass spectrometry (LC-MS). Mass Profiler Professional and Metaboanalyst 4.0 software were used for statistical and pathway analysis. METLIN database was used for the identification of metabolites. We identified 72 differential metabolites compared between CRC cell lines of all the stages and normal colon cells. Principle component analysis and partial least squares discriminant analysis score plot were used to segregate normal and CRC cells, as well as CRC cells in different stages of the disease. Variable importance in projection score identified unique differential metabolites in CRC cells of the different stages. We identified 7 differential metabolites unique to stage A, 3 in stage B, 5 in stage C, and 5 in stage D. This study highlights the differential metabolite profiling in CRC cell lines corresponding to different stages. The identification of the differential metabolites in CRC cells at individual stages will lead to a better understanding of the pathophysiology of CRC development and progression and, hence, its application in treatment strategies.
对各种结直肠癌（CRC）细胞系的代谢组学研究增进了我们对该疾病潜在生化事件的理解。然而，仍缺乏与CRC进展不同阶段相关的代谢谱动态变化信息。此类信息可为该疾病的病理生理学和进展提供进一步的见解，这将有助于识别药物设计和治疗的特定靶点。因此，我们的研究旨在表征与CRC不同阶段相对应的已建立细胞系中的代谢物谱。使用液相色谱 - 质谱联用（LC - MS）对正常结肠细胞系（CCD 841 CoN）以及对应不同阶段的CRC细胞系，即SW 1116（A期）、HT 29和SW 480（B期）、HCT 15和DLD - 1（C期）以及HCT 116（D期）进行代谢物谱分析。使用Mass Profiler Professional和Metaboanalyst 4.0软件进行统计和通路分析。利用METLIN数据库鉴定代谢物。我们鉴定出所有阶段的CRC细胞系与正常结肠细胞之间存在72种差异代谢物。主成分分析和偏最小二乘判别分析得分图用于区分正常细胞和CRC细胞，以及疾病不同阶段的CRC细胞。投影变量重要性得分确定了不同阶段CRC细胞中独特的差异代谢物。我们鉴定出A期特有的7种差异代谢物、B期3种、C期5种以及D期5种。本研究突出了对应不同阶段的CRC细胞系中的差异代谢物谱。鉴定各个阶段CRC细胞中的差异代谢物将有助于更好地理解CRC发生和发展的病理生理学，从而将其应用于治疗策略。
