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Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
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Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics
Rosa Ragone1, Fabio Sallustio2,3,4, Sara Piccinonna5
1Consorzio C.A.R.S.O., Centro di Addestramento e Ricerca Scientifica in Oncologia, Strada Provinciale Casamassima Km 3, Valenzano (Bari) 70010, Italy. rosaragone@yahoo.it.
Diseases (Basel, Switzerland)
|September 22, 2017
Summary
This study reveals key urinary metabolite changes in clear cell renal cell carcinoma (ccRCC) patients using NMR metabolomics. These changes, linked to specific cellular pathways, normalize after kidney removal surgery.
Area of Science:
- Biochemistry
- Oncology
- Metabolomics
Background:
- Renal cell carcinoma (RCC) is a heterogeneous cancer with often-delayed symptoms, necessitating improved diagnostic markers.
- While Mass Spectrometry (MS) dominates metabolomics, Nuclear Magnetic Resonance (NMR)-based studies for RCC diagnosis are limited.
- No prior research has integrated NMR-based metabolomics with transcriptomics for RCC.
Purpose of the Study:
- To investigate urinary metabolic profiles in clear cell RCC (ccRCC) patients using ¹H-NMR spectroscopy.
- To integrate metabolomic findings with transcriptomic data from ccRCC tumoral stem cells.
- To assess the impact of nephrectomy on urinary metabolite profiles in ccRCC patients.
Main Methods:
- ¹H-NMR spectroscopy and multivariate statistics applied to urine samples from 40 ccRCC patients and 29 healthy controls.
- Collection of pre- and post-nephrectomy urine samples from a subset of ccRCC patients.
- Integration of urinary metabolomic data with transcriptomic data from isolated CD133+/CD24+ tumoral renal stem cells.
Main Results:
- Significant alterations in urinary metabolites, including increased creatine, alanine, lactate, and pyruvate, and decreased hippurate, citrate, and betaine in ccRCC patients.
- Network analysis linked these metabolites to glomerular injury, renal inflammation, and renal necrosis/cell death.
- Integrated analysis revealed shared pathways including HIF-α signaling, methionine and choline degradation, and acetyl-CoA biosynthesis between metabolites and transcriptomic data.
Conclusions:
- NMR-based urinary metabolomics combined with transcriptomics provides insights into ccRCC pathophysiology.
- Specific metabolic alterations are associated with key pathological processes in ccRCC.
- Nephrectomy leads to the normalization of urinary metabolic profiles, indicating the tumor's metabolic influence.
