본문 바로가기
KERD
논문KCI 등재

Urinary Metabolites as Biomarkers for Diagnosis of Breast Cancer: A Preliminary Study

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Purpose: For early detection of breast cancer, tests with high sensitivity and specificity are needed. Metabolomics, the study of chemical processes involving metabolites, can be used to identify diagnostic biomarkers for a variety of types of cancers. In this study we identified biomarkers of breast cancer by profiling urinary metabolites. Methods: We performed metabolite profiling of 30 urine samples from 14 patients with breast cancer and 16 healthy controls by liquid chromatography–mass spectrometry. An orthogonal partial least squares-discriminant analysis (OPLS-DA), Student’s t-test, and receiver operating characteristic (ROC) analysis were performed to identify metabolites that were potential diagnostic biomarkers for breast cancer. Results: The OPLS-DA showed clear separation between the two groups. Of the 95 metabolites detected, 24 potential biomarkers were identified by Student’s t-test. A ROC analysis showed that concentrations of N-(2-furoyl)glycine, histidine, and D-tagarose were significantly higher (area under the ROC curve [AUC] >0.7) and those of trigonellinamide, L-galacto-2-heptulose, creatinine, and xanthine were significantly lower (AUC ≥0.8) in the patients with breast cancer than in the healthy controls. Conclusion: Measurement of the concentrations of urinary metabolites can be used to screen for early breast cancer. We plan to explore diagnostic biomarkers of breast cancer in blood and urine further in a larger study.

Abstract

Purpose: For early detection of breast cancer, tests with high sensitivity and specificity are needed. Metabolomics, the study of chemical processes involving metabolites, can be used to identify diagnostic biomarkers for a variety of types of cancers. In this study we identified biomarkers of breast cancer by profiling urinary metabolites. Methods: We performed metabolite profiling of 30 urine samples from 14 patients with breast cancer and 16 healthy controls by liquid chromatography–mass spectrometry. An orthogonal partial least squares-discriminant analysis (OPLS-DA), Student’s t-test, and receiver operating characteristic (ROC) analysis were performed to identify metabolites that were potential diagnostic biomarkers for breast cancer. Results: The OPLS-DA showed clear separation between the two groups. Of the 95 metabolites detected, 24 potential biomarkers were identified by Student’s t-test. A ROC analysis showed that concentrations of N-(2-furoyl)glycine, histidine, and D-tagarose were significantly higher (area under the ROC curve [AUC] >0.7) and those of trigonellinamide, L-galacto-2-heptulose, creatinine, and xanthine were significantly lower (AUC ≥0.8) in the patients with breast cancer than in the healthy controls. Conclusion: Measurement of the concentrations of urinary metabolites can be used to screen for early breast cancer. We plan to explore diagnostic biomarkers of breast cancer in blood and urine further in a larger study.

참고문헌 (25)

  1. Skaane P, "Studies comparing screen-film mammography and full-field digital mammography in breast cancer screening: updated review", Acta radiol, 50, pp.3~14 (2009)
  2. Vander Heiden MG, "Targeting cancer metabolism: a therapeutic window opens", Nat Rev Drug Discov, 10, pp.671~ (2011)
  3. Warburg O, "On the origin of cancer cells", Science, 123, pp.309~314 (1956)
  4. Koppenol WH, "Otto Warburg’s contributions to current concepts of cancer metabolism", Nat Rev Cancer, 11, pp.325~ (2011)
  5. Hsu PP, "Cancer cell metabolism: warburg and beyond", Cell, 134, pp.703~707 (2008)
  6. Wise DR, "Glutamine addiction: a new therapeutic target in cancer", Trends Biochem Sci, 35, pp.427~433 (2010)
  7. Altman BJ, "From Krebs to clinic: glutamine metabolism to cancer therapy", Nat Rev Cancer, 16, pp.619~ (2016)
  8. Chen Y, "RRLC-MS", MS-based metabonomics combined with in-depth analysis of metabolic correlation network: finding potential biomarkers for breast cancer, 2009, pp.134, 2003~2011
  9. Günther UL, "Metabolomics biomarkers for breast cancer", Pathobiology, 82, pp.153~165 (2015)
  10. Johnson C, "Global metabolomics reveals urinary biomarkers of breast cancer in a MCF-7 xenograft mouse model", Metabolites, 3, pp.658~672 (2013)
  11. Henneges C, "Prediction of breast cancer by profiling of urinary RNA metabolites using support vector machine-based feature selection", BMC Cancer, 9, pp.104~ (2009)
  12. Nam H, "Combining tissue transcriptomics and urine metabolomics for breast cancer biomarker identification", Bioinformatics, 25, pp.3151~3157 (2009)
  13. Slupsky CM, "Schepansky A, Capstick V, et al. Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers", Clin Cancer Res, 16, pp.5835~5841 (2010)
  14. Min HK, "Quantitative analysis of urinary phospholipids found in patients with breast cancer by nanoflow liquid chromatography–tandem mass spectrometry: II. Negative ion mode analysis of four phospholipid classes", Anal Bioanal Chem, 396, pp.1273~1280 (2010)
  15. Melone MAB, "The carnitine system and cancer metabolic plasticity", Cell Death Dis, 9, pp.228~ (2018)
  16. Liu Y, "Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer", Prostate Cancer Prostatic Dis, 9, pp.230~ (2006)
  17. Jobard E, "A serum nuclear magnetic resonance-based metabolomic signature of advanced metastatic human breast cancer", Cancer Lett, 343, pp.33~41 (2014)
  18. Qiu Y, "Urinary metabonomic study on colorectal cancer", J Proteome Res, 9, pp.1627~1634 (2010)
  19. Thamer NA, "Detection of xanthine oxidase in breast cancer", Iraqi J Cancer Med Genet, 6 (2018)
  20. Kondo M, "The rate of cell growth is regulated by purine biosynthesis via ATP production and G1 to S phase transition", J Biochem, 128, pp.57~64 (2000)
  21. Kulkarni C, "L-Glutamic acid and glutamine: exciting molecules of clinical interest", Indian J Pharmacol, 37, pp.148~154 (2005)
  22. Budczies J, "Glutamate enrichment as new diagnostic opportunity in breast cancer", Int J Cancer, 136, pp.1619~1628 (2015)
  23. Scalbert A, "Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research", Metabolomics, 56, pp.435~ (2009)
  24. Newgard CB, "Metabolomics and metabolic diseases: where do we stand?", Cell Metab, 25, pp.43~56 (2017)
  25. Riekeberg E, "New frontiers in metabolomics: from measurement to insight", F1000Research, 6, pp.1148~ (2017)

관련 논문AI추천

Application of Metabolic Biomarkers in Breast Cancer: A Literature ReviewLam Ching-Wan, Lee Anbok대한진단검사의학회 · Annals of Laboratory Medicine2025 · 제45권 제3호Metabolic Profiling of Urine Samples from Colorectal Cancer Patients Before and After Surgical Treatments강우영, 김성환, 주종은, 채영기, 한준길, 홍보환한국자기공명학회 · Journal of the Korean Magnetic Resonance Society2010 · 제14권 제1호Profiling of Serum Metabolites Using MALDI-TOF and Triple-TOF Mass Spectrometry to Develop a Screen for Ovarian Cancer김경희, 김승철, 김윤환, 우상명, 유병철, 이준화, 조재열대한암학회 · Cancer Research and Treatment2018 · 제50권 제3호Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls강호원, 김예환, 김운재, 김원태, 김자영, 문성권, 박성혁, 윤석중, 이일석, 정필두, 최영득, 최영현, Chunri Yan, Isaac Yi Kim연세대학교의과대학 · Yonsei Medical Journal2016 · 제57권 제4호Systematic review and meta-analysis of volatile organic compounds (VOCs) for breast cancer screening using the PRISMA approach김주영한국분석과학회 · 분석과학2025 · 제38권 제2호Identification of Hypoxanthine and Phosphoenolpyruvic Acid as Serum Markers of Chemoradiotherapy Response in Locally Advanced Rectal Cancer김건, 여승구, 유병철대한암학회 · Cancer Research and Treatment2015 · 제47권 제1호

이 간행물의 다른 논문 (11건)