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Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract

Background: Colorectal cancer is one of the deadliest diseases with a high prevalence worldwide and is characterized by the appearance of adenomatous polyps in the colon mucosa which are at high risk of developing into colorectal cancer. This study aims to use serum metabolites as promising non-invasive biomarkers for colorectal cancer detection and prognostication. Differences in serum metabolites in patients with adenomatous polyps, colorectal cancer, and healthy controls are considered to be able to support the prognosis of colorectal cancer. Methods: Metabolite dataset is taken from the Metabolomic Workbench. Analysis and validation are carried out in silico using machine learning methods. Results: From a total of 234 samples, 113 metabolites were found and 5 metabolites; histidine, lysine, glyceraldehyde, linolenic acid, and aspartic acid were identified as the most significant in differentiating the sample groups. CTD analysis showed that aspartic acid and histidine are associated with the biological pathways of colorectal cancer progression and significant metabolites are associated with cancer-related phenotypes. Conclusion: The serum metabolites differ in colorectal cancer and healthy control. The significant metabolites can be used as a consideration in selecting colorectal cancer biomarkers, but improvisation is needed to obtain more accurate biomarkers.

Bahasa Abstract

Latar belakang: Kanker kolorektal adalah salah satu penyakit mematikan dengan prevalensi tinggi di dunia dan diawali dengan munculnya polip adenomatosa di mukosa usus besar yang berisiko tinggi berkembang menjadi kanker kolorektal. Penelitian ini bertujuan untuk menggunakan metabolit serum sebagai biomarker non-invasif yang menjanjikan untuk deteksi dan prognostikasi kanker kolorektal. Perbedaan metabolit serum pada pasien polip adenomatosa, kanker kolorektal, dan kontrol sehat dianggap dapat mendukung prognosis kanker kolorektal. Metode: Data metabolit diambil dari Metabolomic Workbench dan identifikasi serta validasi dilakukan secara in silico menggunakan metode machine learning. Hasil: Dari total 234 sampel, ditemukan 113 metabolit dan diidentifikasi 5 metabolit yang paling signifikan membedakan kelompok sampel, yaitu histidine, lysine, glyceraldehyde, linolenic acid, dan aspartic acid. Analisis CTD menunjukan bahwa aspartic acid dan histidin berhubungan dengan jalur biologis progresivitas kanker kolorektal dan berhubungan dengan beberapa fenotip terkait kanker. Simpulan: Metabolit serum dilaporkan berbeda pada kanker kolorektal dan control sehat. Metabolit yang signifikan dapat dipertimbangkan untuk digunakan sebagai biomarker kanker kolorektal, namun diperlukan improvisasi untuk mendapatkan biomarker yang lebih akurat.

References

  1. Vincent Ho, Liping Chung, Stephanie H. Lim, et al. Prognostic impact of TP53 mutations and tumor mutational load in colorectal cancer. Gastrointestinal Disorder. 2022;4:165–179.
  2. Zhu J, et al. Colorectal cancer detection using targeted serum metabolic profiling. J Proteome Res. 2014;13(9):4120-30.
  3. Nguyen, H. T., & Duong, H. Q. The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy. Oncology letters. 2018;16(1), 9–18.
  4. Long Y, et al. Global and targeted serum metabolic profiling of colorectal cancer progression. Cancer. 2017;123(20):4066-4074.
  5. Ritchie SA, Ahiahonu PW, Jayasinghe D, et al. Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection. BMC Med. 2010;8:13.
  6. Wu J, Wu M, Wu Q. Identification of potential metabolite markers for colon cancer and rectal cancer using serum metabolomics. J Clin Lab Anal. 2020;34(8):e23333.
  7. Pitt JJ. Principles and applications of liquid chromatography-mass spectrometry in clinical biochemistry. Clin Biochem Rev. 2009;30(1):19-34.
  8. Moreira J, et al. Systematic Review on the Applicability of Principal Component Analysis for the Study of Movement in the Older Adult Population. Sensors (Basel). 2022;23(1):205.
  9. Zhang Z, Castelló A. Principal components analysis in clinical studies. Ann Transl Med. 2017;5(17):351.
  10. Rothwell, J.A., Bešević, J., Dimou, N. et al. Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts. BMC Med. 2021;80.
  11. Kanarek, N.; Keys, H.R.; Cantor, J.R.; Lewis, C.A.; Chan, S.H.; Kunchok, T.; Abu-Remaileh, M.; Freinkman, E.; Schweitzer, L.D.; Sabatini, D.M. Histidine Catabolism Is a Major Determinant of Methotrexate Sensitivity. Nature. 2018:559, 632–636.
  12. Park, Y.; Han, Y.; Kim, D.; Cho, S.; Kim, W.; Hwang, H.; Lee, H.W.; Han, D.H.; Kim, K.S.; Yun, M.; Lee, M. Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells. Cancers. 2022;14, 1205.
  13. Gold A, Choueiry F, Jin N, Mo X, Zhu J. The application of metobolomics in recent colorectal cancer studies: A state-of-the Art Reviw. Cancers. 2022;14(3):725.
  14. Nishiumi S, Kobayashi T, Ikeda A, Yoshie T, Kibi M, Izumi Y, et al. A novel serum metobolomics-based diagnostic approach for colorectal cancer. PLoS one. 2012;7(7):e404591-10.
  15. Al-Sohaily S, Biankin A, Leong R, Kohonen-Corish M, Warusavitarne J. Molecular pathways in colorectal cancer. Journal of gastroenterology and hepatology. 2012;27(9):1423-31.
  16. Aghagolzadeh P, Radpour R. New trends in molecular and cellular biomarker discovery for colorectal cancer. World journal of gastroenterology. 2016;22(25):5678-93
  17. Stillwater BJ, Bull AC, Romagnolo DF, Neumayer LA, Donovan MG, Selmin OI. Bisphenols and Risk of Breast Cancer: A Narrative Review of the Impact of Diet and Bioactive Food Components. Front Nutr. 2020;7:581388.

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