Diagnosis of post-surgical fine-needle aspiration biopsies of thyroid lesions with indeterminate cytology using HRMAS NMR-based metabolomics

Rezig, Lamya; Servadio, Adele; Torregrossa, Liborio; Miccoli, Paolo; Basolo, Fulvio; Shintu, Laetitia; Caldarelli, Stéfano

doi:10.1007/s11306-018-1437-6

Cited by 26 publications

(31 citation statements)

References 42 publications

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“…The importance of metabolite adaptations and profiling of metabolites in fine-needle aspiration biopsies, surgical biopsies, serum, urine and saliva was shown in various tumor types including breast, liver, thyroid and colorectal cancer (31)(32)(33)(34)(35)(36). However, it is important to note that metabolite profiling in nail materials of cancer patients, including breast cancer has not been reported in literature.…”

Section: Resultsmentioning

confidence: 99%

“…In this direction, several attempts are noticed by using metabolomic approaches, including LC-HRMS, GC-MS and NMR spectroscopy. These metabolomics approaches were focused on the tumor tissue and biological fluids, including serum, urine and saliva (30)(31)(32)(33)(34)(35)(36). However, literature completely lacks on the suitable methods that targets to profile nail metabolites of breast cancer and other tumor types.…”

Section: Introductionmentioning

confidence: 99%

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Undetectable free aromatic amino acids in nails of breast carcinoma: Biomarkers discovery by a novel metabolite purification VTGE system

Mitruka

Gore

Kumar

et al. 2019

Preprint

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BACKGROUND: Metabolic reprogramming in breast cancer is depicted as a crucial change in the tumor microenvironment. Besides the molecular understanding of metabolic heterogeneity, appreciable attentions are drawn to characterize metabolite profiles in tumor tissue and derived biological fluids and tissue materials. Several findings reported on the metabolic alterations of free aromatic amino acids (FAAAs) and other metabolites in biological fluids. Furthermore, there is a significant gap in the development of a suitable method for the purification and analysis of metabolite biomarkers in nails of cancer patients. METHODS: To address the metabolite alterations specifically FAAAs level in nails, fingernail clippings of breast cancer patients (N=10), and healthy subjects (N-12) were used for extraction and purification of metabolites. Here, we report a novel and specifically designed vertical tube gel electrophoresis (VTGE) system that helped for the purification of metabolites in the range of (100-1000 Da) from nail materials. The claimed VTGE system uses 15% polyacrylamide under non-denaturing and non-reducing conditions that makes eluted metabolites directly compatible with LC-HRMS and other analytical techniques. Qualitative and quantitative determination of FAAAs in nail lysates were done by positive ESI mode of Agilent LC-HRMS platform. RESULTS: The analysis on collected data of nail metabolites clearly suggests that FAAAs including tryptophan, tyrosine, phenylalanine and histidine are undetectable in nail lysates of breast cancer over healthy subjects. This is a first report that shows the highly reduced levels of FAAAs in nails of breast cancer. Furthermore, present observation is in consonance with previous findings that support that breast cancer patients show cancer cachexia, high amino acid catabolism that drive metabolite driven cancer growth and proliferation. CONCLUSION: This paper provides a proof of concept for a novel and specifically developed VTGE process that assisted to show the first evidence on undetectable level of FAAAs in nails of breast cancer patients as metabolite biomarkers. Here, the authors propose the potential use of VTGE assisted process to achieve metabolomic discovery in nails of breast cancer and other tumor types.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Undetectable free aromatic amino acids in nails of breast carcinoma: Biomarkers discovery by a novel metabolite purification VTGE system

Mitruka

Gore

Kumar

et al. 2019

Preprint

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“…Several attempts were made in this direction by using metabolomic approaches such as LC-HRMS, GC-MS, and NMR spectroscopy. These metabolomic approaches were focused on the tumor tissue and biological fluids, including serum, urine, and saliva (30)(31)(32)(33)(34)(35)(36).…”

Section: Introductionmentioning

confidence: 99%

Undetectable Free Aromatic Amino Acids in Nails of Breast Carcinoma: Biomarker Discovery by a Novel Metabolite Purification VTGE System

et al. 2020

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“…With increasing burden of breast cancer incidences at global level, around 1.5 million of new cases of breast cancer is projected each year (1)(2). Therefore, comprehensive and novel approaches are warranted to meet the requirements of early diagnosis, monitoring of drug response and new modalities of treatment options (3)(4)(5)(6). Therefore, new area of genomics, proteomics, transcriptomics, epigenomic and metabolomics is set to make advancement in exploring novel classes of biomarkers that can assist in the early detection and drug response monitoring avenues in a global context and Indian setting (3)(4)(5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

“…The importance of metabolic heterogeneity is seen as one of key factors that contribute towards biomarkers development in breast cancer patients (5)(6)(7)(8)(9)(10)(11). Metabolic heterogeneity encompasses various metabolic adaptations including lipid remodeling by breast cancer cells to suffice the metabolic requirements in the tumor microenvironment (9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Novel approach reveals lipid metabolite reduction in nails of breast cancer patients as potential biomarker

Mitruka

Gore

Kumar

et al. 2020

Preprint

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BACKGROUND: Molecular adaptations in intracellular and extracellular microenvironment of breast cancer cells promote pro-tumor metabolic reprogramming. Hence, metabolic reprogramming is seen as a crucial factor in various tumor hallmarks including drug resistance, invasiveness and metastasis. Among well-known metabolic features of breast carcinoma including Warburg effects, altered amino acid metabolism, lipid remodeling is considered as key factors in achieving pro-tumor microenvironment. Therefore, a better understanding on molecular aspects of lipid remodeling is highly appreciated that may contribute towards future therapeutics and diagnostics purpose including the need of potential biomarkers. The identification and validation of lipid biomarkers are reported in the literature, but evidence on lipid metabolites as biomarkers in nails of breast cancer patients is completely unexplored. METHODS: This study reported a novel and specifically designed vertical tube gel electrophoresis (VTGE) system to assist in the purification of metabolites in the range of (~100-1000 Da) from nail samples. Fingernail clippings of breast cancer patients (N=10), and healthy subjects (N-12) were used for extraction and purification of metabolites. The VTGE system uses 15% polyacrylamide under non-denaturing and non-reducing conditions that makes eluted metabolites directly compatible with LC-HRMS and other analytical techniques. The characterization of lipid metabolites in nail lysates was done by positive ESI mode of Agilent LC-HRMS platform. RESULTS: Data suggest a novel observation that healthy and breast cancer patients show distinct accumulation of lipid metabolites specifically choline-based lipids. This is a first report that suggests that levels of choline, phosphorylcholine and lyso-PC are highly reduced and undetectable in nails of breast cancer patients over healthy subject. Furthermore, the potential use of reduced level of choline, phosphorylcholine and lyso-PC in nails of breast cancer patients is in line with current notion that these lipids are diverted to meet the pro-tumor activities in the tumor microenvironment. CONCLUSION: Data strongly provide a proof of concept for the potential use of lipid metabolites including choline, phosphorylcholine and lyso-PC as a set of biomarkers in nails of breast cancer patients. However, the authors propose that validity of these lipid biomarkers may be extended to large population size of breast cancer patients for future applications in early detection, grading, staging, predicting prognosis and therapeutic targeting of breast carcinoma.

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Diagnosis of post-surgical fine-needle aspiration biopsies of thyroid lesions with indeterminate cytology using HRMAS NMR-based metabolomics

Cited by 26 publications

References 42 publications

Undetectable free aromatic amino acids in nails of breast carcinoma: Biomarkers discovery by a novel metabolite purification VTGE system

Undetectable free aromatic amino acids in nails of breast carcinoma: Biomarkers discovery by a novel metabolite purification VTGE system

Undetectable Free Aromatic Amino Acids in Nails of Breast Carcinoma: Biomarker Discovery by a Novel Metabolite Purification VTGE System

Novel approach reveals lipid metabolite reduction in nails of breast cancer patients as potential biomarker

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