{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T05:57:02Z","timestamp":1774677422037,"version":"3.50.1"},"reference-count":79,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology UMIB","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology UMIB","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology UMIB","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"ITR","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}]},{"name":"ITR","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}]},{"name":"ITR","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Amino acids are the building blocks of proteins and essential players in pathways such as the citric acid and urea cycle, purine and pyrimidine biosynthesis, and redox cell signaling. Therefore, it is unsurprising that these molecules have a significant role in cancer metabolism and its metabolic plasticity. As one of the most prevalent malign diseases, colorectal cancer needs biomarkers for its early detection, prognostic, and prediction of response to therapy. However, the available biomarkers for this disease must be more powerful and present several drawbacks, such as high costs and complex laboratory procedures. Metabolomics has gathered substantial attention in the past two decades as a screening platform to study new metabolites, partly due to the development of techniques, such as mass spectrometry or liquid chromatography, which have become standard practice in diagnostic procedures for other diseases. Extensive metabolomic studies have been performed in colorectal cancer (CRC) patients in the past years, and several exciting results concerning amino acid metabolism have been found. This review aims to gather and present findings concerning alterations in the amino acid plasma pool of colorectal cancer patients.<\/jats:p>","DOI":"10.3390\/cancers16010069","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T04:44:40Z","timestamp":1703220280000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Amino Acid Profiles in the Biological Fluids and Tumor Tissue of CRC Patients"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-8895","authenticated-orcid":false,"given":"Marisa Domingues","family":"Santos","sequence":"first","affiliation":[{"name":"Colorectal Unit, Hospital de Santo Ant\u00f3nio, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, 4050-651 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"}]},{"given":"Ivo","family":"Barros","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-7388","authenticated-orcid":false,"given":"Pedro","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Colorectal Unit, Hospital de Santo Ant\u00f3nio, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, 4050-651 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-9535","authenticated-orcid":false,"given":"L\u00facia","family":"Lacerda","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"},{"name":"Genetic Laboratory Service, Centro de Gen\u00e9tica M\u00e9dica Jacinto de Magalh\u00e3es, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, 4050-651 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0140-6736(05)17706-X","article-title":"Colorectal cancer","volume":"365","author":"Weitz","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1055\/s-0029-1242458","article-title":"Colorectal cancer epidemiology: Incidence, mortality, survival, and risk factors","volume":"22","author":"Haggar","year":"2009","journal-title":"Clin. Colon Rectal Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/COH.0b013e32833ed177","article-title":"What are biomarkers?","volume":"5","author":"Strimbu","year":"2010","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gonzalez-Pons, M., and Cruz-Correa, M. (2015). Colorectal Cancer Biomarkers: Where Are We Now?. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/149014"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.2174\/0929867326666190507084839","article-title":"Circulating Biomarkers for Response Prediction of Rectal Cancer to Neoadjuvant Chemoradiotherapy","volume":"27","author":"Bedin","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.1021\/pr400337b","article-title":"Metabonomics identifies serum metabolite markers of colorectal cancer","volume":"12","author":"Tan","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1245\/s10434-011-1638-y","article-title":"Circulating cell-free DNA: A promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy","volume":"18","author":"Agostini","year":"2011","journal-title":"Ann. Surg. Oncol."},{"key":"ref_8","first-page":"226","article-title":"Colorectal Cancer and Metabolism","volume":"14","author":"Brown","year":"2018","journal-title":"Curr. Color. Cancer Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s12276-020-0375-3","article-title":"Amino acids in cancer","volume":"52","author":"Lieu","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nrc1454","article-title":"Polyamines and cancer: Old molecules, new understanding","volume":"4","author":"Gerner","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dias, F., Almeida, C., Teixeira, A.L., Morais, M., and Medeiros, R. (2021). LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020195"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sotelo-Orozco, J., Chen, S.Y., Hertz-Picciotto, I., and Slupsky, C.M. (2021). A Comparison of Serum and Plasma Blood Collection Tubes for the Integration of Epidemiological and Metabolomics Data. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.682134"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yu, Z., Kastenm\u00fcller, G., He, Y., Belcredi, P., M\u00f6ller, G., Prehn, C., Mendes, J., Wahl, S., Roemisch-Margl, W., and Ceglarek, U. (2011). Differences between human plasma and serum metabolite profiles. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021230"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.4155\/bio-2019-0014","article-title":"Analytical techniques for metabolomic studies: A review","volume":"11","author":"Segers","year":"2019","journal-title":"Bioanalysis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7957","DOI":"10.1007\/s00216-013-7127-3","article-title":"Post-column labeling techniques in amino acid analysis by liquid chromatography","volume":"405","author":"Rigas","year":"2013","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-1-61737-985-7_2","article-title":"Amino acid profiling for the diagnosis of inborn errors of metabolism","volume":"708","author":"Piraud","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.1158\/0008-5472.CAN-08-4806","article-title":"Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry","volume":"69","author":"Hirayama","year":"2009","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jpba.2015.11.007","article-title":"Tissue amino acid profile could be used to differentiate advanced adenoma from colorectal cancer","volume":"118","author":"Gao","year":"2016","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/1476-4598-7-72","article-title":"Metabolite profiling of human colon carcinoma--deregulation of TCA cycle and amino acid turnover","volume":"7","author":"Denkert","year":"2008","journal-title":"Mol. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1021\/pr8006232","article-title":"Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC\/MS)","volume":"8","author":"Chan","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/PAI.0b013e318282ac20","article-title":"Immunohistochemical Study of the Nrf2 Pathway in Colorectal Cancer: Nrf2 Expression is Closely Correlated to Keap1 in the Tumor and Bach1 in the Normal Tissue","volume":"21","author":"Chang","year":"2013","journal-title":"Appl. Immunohistochem. Mol. Morphol. AIMM Off. Publ. Soc. Appl. Immunohistochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s11306-008-0151-1","article-title":"Metabolic characterization of primary human colorectal cancers using high resolution magic angle spinning 1 h magnetic resonance spectroscopy","volume":"5","author":"Piotto","year":"2009","journal-title":"Metabolomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4641709","DOI":"10.1155\/2020\/4641709","article-title":"Simultaneous Determination of 34 Amino Acids in Tumor Tissues from Colorectal Cancer Patients Based on the Targeted UHPLC-MS\/MS Method","volume":"2020","author":"Yang","year":"2020","journal-title":"J. Anal. Methods Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1158\/1078-0432.CCR-13-1939","article-title":"A distinct metabolic signature of human colorectal cancer with prognostic potential","volume":"20","author":"Qiu","year":"2014","journal-title":"Clin. Cancer Res. An. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ong, E.S., Zou, L., Li, S., Cheah, P.Y., Eu, K.W., and Ong, C.N. (2010). Metabolic profiling in colorectal cancer reveals signature metabolic shifts during tumorigenesis. Mol. Cell. Proteom. MCP.","DOI":"10.1074\/mcp.M900551-MCP200"},{"key":"ref_26","first-page":"19","article-title":"Increased aspartate and glutamate levels in both gastric and colon cancer tissues","volume":"40","author":"Okada","year":"1993","journal-title":"Tokushima J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/ijc.32190","article-title":"(1) H NMR-based metabolomics reveal overlapping discriminatory metabolites and metabolic pathway disturbances between colorectal tumor tissues and fecal samples","volume":"145","author":"Lin","year":"2019","journal-title":"Int. J. Cancer."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rodriguez-Tomas, E., Arenas, M., Gomez, J., Acosta, J., Trilla, J., Lopez, Y., Arquez, M., Torres, L., Araguas, P., and Hernandez-Aguilera, A. (2021). Identification of potential metabolic biomarkers of rectal cancer and of the effect of neoadjuvant radiochemotherapy. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250453"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"727","DOI":"10.21037\/atm.2019.12.34","article-title":"A gas chromatography-mass spectrometry (GC-MS) metabolomic approach in human colorectal cancer (CRC): The emerging role of monosaccharides and amino acids","volume":"7","author":"Barberini","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s11306-011-0357-5","article-title":"Serum amino acid profiles and their alterations in colorectal cancer","volume":"8","author":"Leichtle","year":"2012","journal-title":"Metabolomics"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Miyagi, Y., Higashiyama, M., Gochi, A., Akaike, M., Ishikawa, T., Miura, T., Saruki, N., Bando, E., Kimura, H., and Imamura, F. (2011). Plasma free amino acid profiling of five types of cancer patients and its application for early detection. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024143"},{"key":"ref_32","first-page":"1269","article-title":"Plasma amino acid levels in patients with colorectal cancers and liver cirrhosis with hepatocellular carcinoma","volume":"50","author":"Lee","year":"2003","journal-title":"Hepato-Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.tibs.2010.05.003","article-title":"Glutamine addiction: A new therapeutic target in cancer","volume":"35","author":"Wise","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Troisi, J., Tafuro, M., Lombardi, M., Scala, G., Richards, S.M., Symes, S.J.K., Ascierto, P.A., Delrio, P., Tatangelo, F., and Buonerba, C. (2022). A Metabolomics-Based Screening Proposal for Colorectal Cancer. Metabolites, 12.","DOI":"10.3390\/metabo12020110"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3491852","DOI":"10.1155\/2019\/3491852","article-title":"Metabolomics Analysis in Serum from Patients with Colorectal Polyp and Colorectal Cancer by 1H-NMR Spectrometry","volume":"2019","author":"Gu","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1021\/pr500494u","article-title":"Colorectal cancer detection using targeted serum metabolic profiling","volume":"13","author":"Zhu","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4844","DOI":"10.1021\/pr9004162","article-title":"Serum metabolite profiling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS","volume":"8","author":"Qiu","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/S0006-2952(03)00504-5","article-title":"The changing faces of glutathione, a cellular protagonist","volume":"66","author":"Pompella","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/nm934","article-title":"Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase","volume":"9","author":"Uyttenhove","year":"2003","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1038\/sj.bjc.6600336","article-title":"Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer","volume":"86","author":"Huang","year":"2002","journal-title":"Br. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1080\/15384101.2018.1442625","article-title":"LINP1 facilitates DNA damage repair through non-homologous end joining (NHEJ) pathway and subsequently decreases the sensitivity of cervical cancer cells to ionizing radiation","volume":"17","author":"Wang","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nishiumi, S., Kobayashi, T., Ikeda, A., Yoshie, T., Kibi, M., Izumi, Y., Okuno, T., Hayashi, N., Kawano, S., and Takenawa, T. (2012). A novel serum metabolomics-based diagnostic approach for colorectal cancer. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040459"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17115","DOI":"10.18632\/oncotarget.15081","article-title":"Investigations in the possibility of early detection of colorectal cancer by gas chromatography\/triple-quadrupole mass spectrometry","volume":"8","author":"Nishiumi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e23333","DOI":"10.1002\/jcla.23333","article-title":"Identification of potential metabolite markers for colon cancer and rectal cancer using serum metabolomics","volume":"34","author":"Wu","year":"2020","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1002\/ijc.32146","article-title":"Plasma metabolites associated with colorectal cancer: A discovery-replication strategy","volume":"145","author":"Geijsen","year":"2019","journal-title":"Int. J. Cancer."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/bjc.2016.243","article-title":"A validated metabolomic signature for colorectal cancer: Exploration of the clinical value of metabolomics","volume":"115","author":"Farshidfar","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1097\/SLA.0b013e31824a9a8b","article-title":"An integrated proteomics and metabolomics approach for defining oncofetal biomarkers in the colorectal cancer","volume":"255","author":"Ma","year":"2012","journal-title":"Ann. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105819","DOI":"10.18632\/oncotarget.22402","article-title":"NMR-based metabolomic techniques identify potential urinary biomarkers for early colorectal cancer detection","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1002\/ijc.32666","article-title":"Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium","volume":"146","author":"Geijsen","year":"2020","journal-title":"Int. J. Cancer."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Di Donato, S., Vignoli, A., Biagioni, C., Malorni, L., Mori, E., Tenori, L., Calamai, V., Parnofiello, A., Di Pierro, G., and Migliaccio, I. (2021). A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting. Cancers, 13.","DOI":"10.3390\/cancers13112762"},{"key":"ref_51","first-page":"835","article-title":"Staging of colorectal cancer using serum metabolomics with 1HNMR Spectroscopy","volume":"20","author":"Vahabi","year":"2017","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/gm341","article-title":"Serum metabolomic profile as a means to distinguish stage of colorectal cancer","volume":"4","author":"Farshidfar","year":"2012","journal-title":"Genome Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.radonc.2015.11.031","article-title":"High tumor glycine concentration is an adverse prognostic factor in locally advanced rectal cancer","volume":"118","author":"Redalen","year":"2016","journal-title":"Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ling, H.H., Pan, Y.P., Fan, C.W., Tseng, W.K., Huang, J.S., Wu, T.H., Chou, W.C., Wang, C.H., Yeh, K.Y., and Chang, P.H. (2019). Clinical Significance of Serum Glutamine Level in Patients with Colorectal Cancer. Nutrients, 11.","DOI":"10.3390\/nu11040898"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/s41416-018-0357-6","article-title":"Alterations in serum amino-acid profile in the progression of colorectal cancer: Associations with systemic inflammation, tumour stage and patient survival","volume":"120","author":"Sirnio","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s12967-022-03523-3","article-title":"Glutamine deficiency promotes recurrence and metastasis in colorectal cancer through enhancing epithelial-mesenchymal transition","volume":"20","author":"Sun","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1158\/0008-5472.CAN-11-1543","article-title":"Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer","volume":"72","author":"Bertini","year":"2012","journal-title":"Cancer Res."},{"key":"ref_58","first-page":"572149","article-title":"Tumor regression grades: Can they influence rectal cancer therapy decision tree?","volume":"2013","author":"Santos","year":"2013","journal-title":"Int. J. Surg. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"310542","DOI":"10.1155\/2014\/310542","article-title":"Prognostic value of mandard and dworak tumor regression grading in rectal cancer: Study of a single tertiary center","volume":"2014","author":"Santos","year":"2014","journal-title":"ISRN Surg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s11306-018-1406-0","article-title":"Metabolomics approach for predicting response to neoadjuvant chemotherapy for colorectal cancer","volume":"14","author":"Yang","year":"2018","journal-title":"Metabolomics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.radonc.2018.06.022","article-title":"Predicting the pathological response to neoadjuvant chemoradiation using untargeted metabolomics in locally advanced rectal cancer","volume":"128","author":"Jia","year":"2018","journal-title":"Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"583228","DOI":"10.3389\/fonc.2020.583228","article-title":"Tryptophan Catabolism and Response to Therapy in Locally Advanced Rectal Cancer (LARC) Patients","volume":"10","author":"Crotti","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1126\/science.122.3168.501","article-title":"Nutrition needs of mammalian cells in tissue culture","volume":"122","author":"Eagle","year":"1955","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.lungcan.2015.10.006","article-title":"The performance of a novel amino acid multivariate index for detecting lung cancer: A case control study in Korea","volume":"90","author":"Kim","year":"2015","journal-title":"Lung Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/00365513.2018.1542541","article-title":"The decrease of some serum free amino acids can predict breast cancer diagnosis and progression","volume":"79","author":"Eniu","year":"2019","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2291759","DOI":"10.1155\/2020\/2291759","article-title":"Prognostic Role of Serum Amino Acids in Head and Neck Cancer","volume":"2020","author":"Cadoni","year":"2020","journal-title":"Dis. Markers"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1126\/science.1218595","article-title":"Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation","volume":"336","author":"Jain","year":"2012","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/MCO.0000000000000430","article-title":"Branched-chain amino acid metabolism in cancer","volume":"21","author":"Ananieva","year":"2018","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1158\/1541-7786.MCR-18-0362","article-title":"A Role for Tryptophan-2,3-dioxygenase in CD8 T-cell Suppression and Evidence of Tryptophan Catabolism in Breast Cancer Patient Plasma","volume":"17","author":"Greene","year":"2019","journal-title":"Mol. Cancer Res. MCR"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"769501","DOI":"10.3389\/fphar.2021.769501","article-title":"New Insights Into Gut-Bacteria-Derived Indole and Its Derivatives in Intestinal and Liver Diseases","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1039\/C4MB00054D","article-title":"A metabolomics approach for predicting the response to neoadjuvant chemotherapy in cervical cancer patients","volume":"10","author":"Hou","year":"2014","journal-title":"Mol. Biosyst."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.molonc.2012.10.003","article-title":"Metabolomics approach for predicting response to neoadjuvant chemotherapy for breast cancer","volume":"7","author":"Wei","year":"2013","journal-title":"Mol. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"He, X., Gu, J., Zou, D., Yang, H., Zhang, Y., Ding, Y., and Teng, L. (2021). NMR-Based Metabolomics Analysis Predicts Response to Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.708052"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1681\/ASN.2020071077","article-title":"Kidney Failure Prediction Models: A Comprehensive External Validation Study in Patients with Advanced CKD","volume":"32","author":"Ramspek","year":"2021","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1016\/j.csbj.2020.09.033","article-title":"Deep metabolome: Applications of deep learning in metabolomics","volume":"18","author":"Pomyen","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1038\/s41467-020-17347-6","article-title":"Machine learning of serum metabolic patterns encodes early-stage lung adenocarcinoma","volume":"11","author":"Huang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s10549-021-06310-8","article-title":"Prediction of pathologic complete response to neoadjuvant chemotherapy using machine learning models in patients with breast cancer","volume":"189","author":"Kim","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/cac2.12310","article-title":"Spatial metabolomics for evaluating response to neoadjuvant therapy in non-small cell lung cancer patients","volume":"42","author":"Shen","year":"2022","journal-title":"Cancer Commun"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"807264","DOI":"10.3389\/fonc.2022.807264","article-title":"Deep Learning Model for Predicting the Pathological Complete Response to Neoadjuvant Chemoradiotherapy of Locally Advanced Rectal Cancer","volume":"12","author":"Lou","year":"2022","journal-title":"Front. 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