| Texto completo | |
| Autor(es): Mostrar menos - |
Cai, Yuping
[1]
;
Rattray, Nicholas J. W.
[2, 1]
;
Zhang, Qian
[1]
;
Mironova, Varvara
[1]
;
Santos-Neto, Alvaro
[3, 1]
;
Muca, Engjel
[4]
;
Vollmar, Ana K. Rosen
[1]
;
Hsu, Kuo-Shun
[4]
;
Rattray, Zahra
[2]
;
Cross, Justin R.
[5]
;
Zhang, Yawei
[1, 6]
;
Paty, Philip B.
[4]
;
Khan, Sajid A.
[7]
;
Johnson, Caroline H.
[1]
Número total de Autores: 14
|
| Afiliação do(s) autor(es): | [1] Yale Univ, Yale Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 - USA
[2] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G4 0RE, Lanark - Scotland
[3] Univ Sao Paulo, Sao Carlos Inst Chem, BR-13566590 Sao Carlos - Brazil
[4] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 - USA
[5] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 - USA
[6] Yale Univ, Dept Surg, Sch Med, New Haven, CT 06520 - USA
[7] Yale Univ, Dept Surg, Div Surg Oncol, Sch Med, New Haven, CT 06520 - USA
Número total de Afiliações: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | METABOLITES; v. 10, n. 6 JUN 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
The progress in the discovery and validation of metabolite biomarkers for the detection of colorectal cancer (CRC) has been hampered by the lack of reproducibility between study cohorts. The majority of discovery-phase biomarker studies have used patient blood samples to identify disease-related metabolites, but this pre-validation phase is confounded by non-specific disease influences on the metabolome. We therefore propose that metabolite biomarker discovery would have greater success and higher reproducibility for CRC if the discovery phase was conducted in tumor tissues, to find metabolites that have higher specificity to the metabolic consequences of the disease, that are then validated in blood samples. This would thereby eliminate any non-tumor and/or body response effects to the disease. In this study, we performed comprehensive untargeted metabolomics analyses on normal (adjacent) colon and tumor tissues from CRC patients, revealing tumor tissue-specific biomarkers (n= 39/group). We identified 28 highly discriminatory tumor tissue metabolite biomarkers of CRC by orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate analyses (VIP > 1.5,p< 0.05). A stepwise selection procedure was used to identify nine metabolites that were the most predictive of CRC with areas under the curve (AUCs) of >0.96, using various models. We further identified five biomarkers that were specific to the anatomic location of tumors in the colon (n= 236). The combination of these five metabolites (S-adenosyl-L-homocysteine, formylmethionine, fucose 1-phosphate, lactate, and phenylalanine) demonstrated high differentiative capability for left- and right-sided colon cancers at stage I by internal cross-validation (AUC = 0.804, 95% confidence interval, CI 0.670-0.940). This study thus revealed nine discriminatory biomarkers of CRC that are now poised for external validation in a future independent cohort of samples. We also discovered a discrete metabolic signature to determine the anatomic location of the tumor at the earliest stage, thus potentially providing clinicians a means to identify individuals that could be triaged for additional screening regimens. (AU) | |
| Processo FAPESP: | 18/01448-9 - Preparo de amostras e LC-MS para análises metabolômica e expossômica: estudos e aplicação para matrizes biológicas diversas |
| Beneficiário: | Alvaro José dos Santos Neto |
| Modalidade de apoio: | Bolsas no Exterior - Pesquisa |