Write your message
Volume 18, Issue 3 (Iranian Journal of Breast Diseases 2025)                   ijbd 2025, 18(3): 52-84 | Back to browse issues page


XML Persian Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Nobakht M. Gh. B F, Gilany K. Amino Acid Profile Alterations in Breast Cancer: A Systematic Review and Meta-Analysis. ijbd 2025; 18 (3) :52-84
URL: http://ijbd.ir/article-1-1173-en.html
1- Chemical Injuries Research Center, Systems Biology and Poisoning Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
2- Molecular Engineering & Sciences Institute, Arak University, Arak 3848177584, Iran. & Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran 1983969412, Iran. Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran 1517964311, Iran , k.gilany@avicenna.ac.ir
Abstract:   (567 Views)
Introduction: Breast cancer (BC) is one of the most common malignancies in women, and its early detection plays a crucial role in improving treatment outcomes. In this regard, the identification of novel biomarkers that can contribute to earlier and more accurate diagnosis of this disease is of paramount importance. This meta-analysis was designed to evaluate the feasibility of serum or plasma amino acid concentrations as potential biomarkers for BC.
Methods: A systematic literature search was conducted in PubMed, Scopus, and Embase databases using relevant keywords. The search encompassed all online publications from inception to February 1, 2025. Eligible studies were analyzed using MedCalc software for meta-analysis. Standardized mean differences (SMD) and standard deviations (SD) were used to assess alterations in serum/plasma amino acid levels. Due to high heterogeneity between studies, a random-effects model was employed in the meta-analysis.
Results: A total of twelve studies, involving 1849 participants, met the inclusion criteria for the meta-analysis. Our results showed significant changes in only two out of 20 amino acids when comparing BC patients to the control group. Individuals with BC exhibited significantly lower serum/plasma tryptophan levels levels than the control group, while serine levels were increased in the patient population compared to controls.
Conclusion: The results of this study demonstrated significant alterations in serum/plasma tryptophan and serine levels in patients with BC. These changes may serve as a foundation for the development of novel diagnostic methods and the improvement of therapeutic approaches for BC.
Full-Text [PDF 2954 kb]   (94 Downloads)    
Type of Study: review | Subject: Diagnosis, treatment, rehabilitation
Received: 2025/03/1 | Accepted: 2025/06/1 | Published: 2025/10/2

References
1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: a cancer journal for clinicians. 2023;73(1):17-48. doi: 10.3322/caac.21763 [DOI:10.3322/caac.21763] [PMID]
2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-49. doi: 10.3322/caac.21660 [DOI:10.3322/caac.21660] [PMID]
3. Kim J, Harper A, McCormack V, Sung H, Houssami N, Morgan E, et al. Global patterns and trends in breast cancer incidence and mortality across 185 countries. Nature Medicine. 2025:1-9. doi: 10.1038/s41591-025-03502-3 [DOI:10.1038/s41591-025-03502-3] [PMID]
4. Seyed-Nezhad M, Effatpanah M, Moradi T, Akbari M, Manzouri L, Moradi-Joo M. Incidence, Prevalence, Mortality, and Direct Costs of Breast Cancer in Iran: Using the Iran Health Insurance Organization Database. cancer. 2025;1:2. doi: 10.5812/ijcm-157981 [DOI:10.5812/ijcm-157981]
5. Sanaat Z, Dolatkhah R. Epidemiologic profile of breast cancer in Iran: a systematic review and meta-analysis. Clinical Epidemiology and Global Health. 2024;26:101537. doi: 10.1016/j.cegh.2024.101537 [DOI:10.1016/j.cegh.2024.101537]
6. Jiao Z, Pan Y, Chen F. The metabolic landscape of breast cancer and its therapeutic implications. Molecular Diagnosis & Therapy. 2023;27(3):349-69. doi: 10.1007/s40291-023-00645-2 [DOI:10.1007/s40291-023-00645-2] [PMID]
7. Li S, Zeng H, Fan J, Wang F, Xu C, Li Y, et al. Glutamine metabolism in breast cancer and possible therapeutic targets. Biochemical pharmacology. 2023;210:115464. doi: 10.1016/j.bcp.2023.115464 [DOI:10.1016/j.bcp.2023.115464] [PMID]
8. Jové M, Collado R, Quiles JL, Ramírez-Tortosa M-C, Sol J, Ruiz-Sanjuan M, et al. A plasma metabolomic signature discloses human breast cancer. Oncotarget. 2017;8(12):19522. doi: 10.18632/oncotarget.14521 [DOI:10.18632/oncotarget.14521] [PMID] []
9. Jasbi P, Wang D, Cheng SL, Fei Q, Cui JY, Liu L, et al. Breast cancer detection using targeted plasma metabolomics. Journal of chromatography B. 2019;1105:26-37. doi: 10.1016/j.jchromb.2018.11.029 [DOI:10.1016/j.jchromb.2018.11.029] [PMID]
10. Nobakht M. Gh BF, Aliannejad R, Rezaei-Tavirani M, Taheri S, Oskouie AA. The metabolomics of airway diseases, including COPD, asthma and cystic fibrosis. Biomarkers. 2015;20(1):5-16. doi: 10.3109/1354750X.2014.983167 [DOI:10.3109/1354750X.2014.983167] [PMID]
11. Dougan MM, Li Y, Chu LW, Haile RW, Whittemore AS, Han SS, et al. Metabolomic profiles in breast cancer: a pilot case-control study in the breast cancer family registry. BMC cancer. 2018;18:1-8. doi: 10.1186/s12885-018-4437-z [DOI:10.1186/s12885-018-4437-z] [PMID] []
12. Shen J, Yan L, Liu S, Ambrosone CB, Zhao H. Plasma metabolomic profiles in breast cancer patients and healthy controls: by race and tumor receptor subtypes. Translational oncology. 2013;6(6):757. doi: 10.1593/tlo.13619 [DOI:10.1593/tlo.13619] [PMID] []
13. Jobard E, Pontoizeau C, Blaise BJ, Bachelot T, Elena-Herrmann B, Trédan O. A serum nuclear magnetic resonance-based metabolomic signature of advanced metastatic human breast cancer. Cancer letters. 2014;343(1):33-41. doi: 10.1016/j.canlet.2013.09.011 [DOI:10.1016/j.canlet.2013.09.011] [PMID]
14. Mishra P, Ambs S. Metabolic signatures of human breast cancer. Molecular & cellular oncology. 2015;2(3):e992217. doi: 10.4161/23723556.2014.992217 [DOI:10.4161/23723556.2014.992217] [PMID] []
15. Fan Y, Zhou X, Xia T-S, Chen Z, Li J, Liu Q, et al. Human plasma metabolomics for identifying differential metabolites and predicting molecular subtypes of breast cancer. Oncotarget. 2016;7(9):9925. doi: 10.18632/oncotarget.7155 [DOI:10.18632/oncotarget.7155] [PMID] []
16. Asiago VM, Alvarado LZ, Shanaiah N, Gowda GN, Owusu-Sarfo K, Ballas RA, Raftery D. Early detection of recurrent breast cancer using metabolite profiling. Cancer research. 2010;70(21):8309-18. doi: 10.1158/0008-5472.CAN-10-1319 [DOI:10.1158/0008-5472.CAN-10-1319] [PMID] []
17. Zapater-Moros A, Díaz-Beltrán L, Gámez-Pozo A, Trilla-Fuertes L, Lumbreras-Herrera MI, López-Camacho E, et al. Metabolomics unravels subtype-specific characteristics related to neoadjuvant therapy response in breast cancer patients. Metabolomics. 2023;19(7):60. doi: 10.1007/s11306-023-02024-8 [DOI:10.1007/s11306-023-02024-8] [PMID]
18. Slupsky CM, Steed H, Wells TH, Dabbs K, Schepansky A, Capstick V, et al. Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers. Clinical cancer research. 2010;16(23):5835-41. doi: 10.1158/1078-0432.CCR-10-1434 [DOI:10.1158/1078-0432.CCR-10-1434] [PMID]
19. Murata T, Yanagisawa T, Kurihara T, Kaneko M, Ota S, Enomoto A, et al. Salivary metabolomics with alternative decision tree-based machine learning methods for breast cancer discrimination. Breast cancer research and treatment. 2019;177:591-601. doi: 10.1007/s10549-019-05330-9 [DOI:10.1007/s10549-019-05330-9] [PMID]
20. Yuan B, Schafferer S, Tang Q, Scheffler M, Nees J, Heil J, et al. A plasma metabolite panel as biomarkers for early primary breast cancer detection. International journal of cancer. 2019;144(11):2833-42. doi: 10.1002/ijc.31996 [DOI:10.1002/ijc.31996] [PMID]
21. Eniu DT, Romanciuc F, Moraru C, Goidescu I, Eniu D, Staicu A, et al. The decrease of some serum free amino acids can predict breast cancer diagnosis and progression. Scandinavian journal of clinical and laboratory investigation. 2019;79(1-2):17-24. doi: 10.1080/00365513.2018.1542541 [DOI:10.1080/00365513.2018.1542541] [PMID]
22. More TH, RoyChoudhury S, Christie J, Taunk K, Mane A, Santra MK, et al. Metabolomic alterations in invasive ductal carcinoma of breast: A comprehensive metabolomic study using tissue and serum samples. Oncotarget. 2018;9(2):2678. doi: 10.18632/oncotarget.23626 [DOI:10.18632/oncotarget.23626] [PMID] []
23. Torata N, Kubo M, Miura D, Ohuchida K, Mizuuchi Y, Fujimura Y, et al. Visualizing energy charge in breast carcinoma tissues by MALDI mass-spectrometry imaging profiles of low-molecular-weight metabolites. Anticancer research. 2018;38(7):4267-72. doi: 10.21873/anticanres.12723 [DOI:10.21873/anticanres.12723] [PMID]
24. Baranovicova E, Racay P, Zubor P, Smolar M, Kudelova E, Halasova E, et al. Circulating metabolites in the early stage of breast cancer were not related to cancer stage or subtypes but associated with ki67 level. Promising statistical discrimination from controls. Molecular and Cellular Probes. 2022;66:101862. doi: 10.1016/j.mcp.2022.101862 [DOI:10.1016/j.mcp.2022.101862] [PMID]
25. Hussain A, Xie L, Deng G, Kang X. Common alterations in plasma free amino acid profiles and gut microbiota-derived tryptophan metabolites of five types of cancer patients. Amino Acids. 2023;55(9):1189-200. doi: 10.1007/s00726-023-03308-y [DOI:10.1007/s00726-023-03308-y] [PMID]
26. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic reviews. 2015;4:1-9. doi: 10.1186/2046-4053-4-1 [DOI:10.1186/2046-4053-4-1] [PMID] []
27. https://www.ohri.ca/programs/ clinical_epidemiology/oxford.asp [
28. Wang X, Zhao X, Chou J, Yu J, Yang T, Liu L, Zhang F. Taurine, glutamic acid and ethylmalonic acid as important metabolites for detecting human breast cancer based on the targeted metabolomics. Cancer biomarkers. 2018;23(2):255-68. doi: 10.3233/CBM-181500 [DOI:10.3233/CBM-181500] [PMID]
29. Gu Y, Chen T, Fu S, Sun X, Wang L, Wang J, et al. Perioperative dynamics and significance of amino acid profiles in patients with cancer. Journal of translational medicine. 2015;13:1-14. doi: 10.1186/s12967-015-0408-1 [DOI:10.1186/s12967-015-0408-1] [PMID] []
30. Miyagi Y, Higashiyama M, Gochi A, Akaike M, Ishikawa T, Miura T, et al. Plasma free amino acid profiling of five types of cancer patients and its application for early detection. PloS one. 2011;6(9):e24143. doi: 10.1371/journal.pone.0024143 [DOI:10.1371/journal.pone.0024143] [PMID] []
31. Okamoto N, Miyagi Y, Chiba A, Akaike M, Shiozawa M, Imaizumi A, et al. Diagnostic modeling with differences in plasma amino acid profiles between non-cachectic colorectal/breast cancer patients and healthy individuals. International Journal of Medical Sciences. 2009;1(1):1-8.
32. Kubota A, Meguid MM, Hitch DC. Amino acid profiles correlate diagnostically with organ site in three kinds of malignant tumors. Cancer. 1992;69(9):2343-8. doi: 10.1002/1097-0142(19920501)69:9<2343: aid-cncr2820690924>3.0.co;2-s https://doi.org/10.1002/1097-0142(19920501)69:9<2343::AID-CNCR2820690924>3.0.CO;2-S [DOI:10.1002/1097-0142(19920501)69:93.0.CO;2-S] [PMID]
33. Minet-Quinard R, Van Praagh I, Kwiatkowski F, Beaujon G, Feillel V, Beaufrère B, et al. Pre-and postoperative aminoacidemia in breast cancer: a study vs. matched healthy subjects. Cancer investigation. 2004;22(2):203-10. doi: 10.1081/cnv-120030208 [DOI:10.1081/CNV-120030208] [PMID]
34. Proenza AM, Oliver J, Palou A, Roca P. Breast and lung cancer are associated with a decrease in blood cell amino acid content. The Journal of nutritional biochemistry. 2003;14 (3):133-8. doi: 10.1016/s0955-2863(02)00225-5 [DOI:10.1016/S0955-2863(02)00225-5] [PMID]
35. Vissers YL, Dejong CH, Luiking YC, Fearon KC, von Meyenfeldt MF, Deutz NE. Plasma arginine concentrations are reduced in cancer patients: evidence for arginine deficiency? The American journal of clinical nutrition. 2005;81(5):1142-6. doi: 10.1093/ajcn/81.5.1142 [DOI:10.1093/ajcn/81.5.1142] [PMID]
36. Poschke I, Mao Y, Kiessling R, de Boniface J. Tumor-dependent increase of serum amino acid levels in breast cancer patients has diagnostic potential and correlates with molecular tumor subtypes. Journal of translational medicine. 2013;11:1-9. doi: 10.1186/1479-5876-11-290 [DOI:10.1186/1479-5876-11-290] [PMID] []
37. Barnes T, Bell K, DiSebastiano KM, Vance V, Hanning R, Russell C, et al. Plasma amino acid profiles of breast cancer patients early in the trajectory of the disease differ from healthy comparison groups. Applied Physiology, Nutrition, and Metabolism. 2014;39(6):740-4. doi: 10.1139/apnm-2013-0526. [DOI:10.1139/apnm-2013-0526] [PMID]
38. Panigoro SS, Kurniawan A, Ramadhan R, Sukartini N, Herqutanto H, Paramita RI, Sandra F. Amino acid profile of luminal A and B subtypes breast cancer. The Indonesian Biomedical Journal. 2023;15(3):269-76. doi: 10.18585/inabj.v15i3.2109 [DOI:10.18585/inabj.v15i3.2109]
39. di Meo NA, Loizzo D, Pandolfo SD, Autorino R, Ferro M, Porta C, et al. Metabolomic approaches for detection and identification of biomarkers and altered pathways in bladder cancer. International Journal of Molecular Sciences. 2022;23(8):4173. doi: 10.3390/ijms23084173 [DOI:10.3390/ijms23084173] [PMID] []
40. Kelly RS, Vander Heiden MG, Giovannucci E, Mucci LA. Metabolomic biomarkers of prostate cancer: prediction, diagnosis, progression, prognosis, and recurrence. Cancer Epidemiology, Biomarkers & Prevention. 2016;25(6):887-906. doi: 10.1158/1055-9965.EPI-15-1223 [DOI:10.1158/1055-9965.EPI-15-1223] [PMID] []
41. Monteiro MS, Carvalho M, de Lourdes Bastos M, de Pinho PG. Biomarkers in renal cell carcinoma: a metabolomics approach. Metabolomics. 2014;10:1210-22. doi: 10.1007/s11306-014-0659-5 [DOI:10.1007/s11306-014-0659-5]
42. Wei Y, Jasbi P, Shi X, Turner C, Hrovat J, Liu L, et al. Early breast cancer detection using untargeted and targeted metabolomics. Journal of proteome research. 2021;20 (6): 3124-3133. doi: 10.1021/acs.jproteome.1c00019 [DOI:10.1021/acs.jproteome.1c00019] [PMID]
43. Yang L, Wang Y, Cai H, Wang S, Shen Y, Ke C. Application of metabolomics in the diagnosis of breast cancer: a systematic review. Journal of Cancer. 2020;11(9):2540. doi: 10.7150/jca.37604 [DOI:10.7150/jca.37604] [PMID] []
44. Puchades-Carrasco L, Jantus-Lewintre E, Pérez-Rambla C, García-García F, Lucas R, Calabuig S, et al. Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer. Oncotarget. 2016;7(11):12904. doi: 10.18632/oncotarget.7354 [DOI:10.18632/oncotarget.7354] [PMID] []
45. Isla Larrain MT, Rabassa ME, Lacunza E, Barbera A, Cretón A, Segal-Eiras A, et al. IDO is highly expressed in breast cancer and breast cancer-derived circulating microvesicles and associated to aggressive types of tumors by in silico analysis. Tumor Biology. 2014;35:6511-9. doi: 10.1007/s13277-014-1859-3 [DOI:10.1007/s13277-014-1859-3] [PMID]
46. Chen J-Y, Li C-F, Kuo C-C, Tsai KK, Hou M-F, Hung W-C. Cancer/stroma interplay via cyclooxygenase-2 and indoleamine 2, 3-dioxygenase promotes breast cancer progression. Breast Cancer Research. 2014;16:1-14. doi: 10.1186/s13058-014-0410-1. [DOI:10.1186/s13058-014-0410-1] [PMID] []
47. Lyon DE, Walter JM, Starkweather AR, Schubert CM, McCain NL. Tryptophan degradation in women with breast cancer: a pilot study. BMC research notes. 2011;4:1-7. doi: 10.1186/1756-0500-4-156 [DOI:10.1186/1756-0500-4-156] [PMID] []
48. Liu T, Liu C, Song M, Wei Y, Song Y, Chen P, et al. The association of serum serine levels with the risk of incident cancer: results from a nested case-control study. Food & Function. 2023;14(17):7969-76. doi: 10.1039/d3fo00808h [DOI:10.1039/D3FO00808H] [PMID]
49. Kim SK, Jung WH, Koo JS. Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes. PloS one. 2014;9(6):e101004. doi: 10.1371/journal.pone.0101004 [DOI:10.1371/journal.pone.0101004] [PMID] []
50. Sullivan MR, Mattaini KR, Dennstedt EA, Nguyen AA, Sivanand S, Reilly MF, et al. Increased serine synthesis provides an advantage for tumors arising in tissues where serine levels are limiting. Cell metabolism. 2019;29(6):1410-21. e4. doi: 10.1016/j.cmet.2019.02.015 [DOI:10.1016/j.cmet.2019.02.015] [PMID] []
51. Noh S, Kim DH, Jung WH, Koo JS. Expression levels of serine/glycine metabolism-related proteins in triple negative breast cancer tissues. Tumor Biology. 2014;35:4457-68. doi: 10.1007/s13277-013-1588-z [DOI:10.1007/s13277-013-1588-z] [PMID]
52. DeNicola GM, Chen P-H, Mullarky E, Sudderth JA, Hu Z, Wu D, et al. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nature genetics. 2015;47(12):1475-81. doi: 10.1038/ng.3421. [DOI:10.1038/ng.3421] [PMID] []

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2025 CC BY-NC 4.0 | Iranian Journal of Breast Diseases

Designed & Developed by: Yektaweb