Objectives:To date,predictive and prognostic biomarkers for Bladder Cancer(BC)remain lacking.Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification.The primary ob...Objectives:To date,predictive and prognostic biomarkers for Bladder Cancer(BC)remain lacking.Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification.The primary objective of this study is to characterize the serum metabolic profile of BC patients undergoing platinumbased chemotherapy(Pt-CT)to identify potential biomarkers.Methods:In this pilot study,we investigated the metabolomic profiles of 14 BC patients undergoing Pt-CT in different settings.We compared their baseline profiles with those of healthy controls and tracked key metabolites throughout chemotherapy cycles.Metabolomics profiling was conducted using nuclear magnetic resonance(NMR)spectroscopy.All experiments were performed on a Bruker Avance™600 spectrometer.Results:Serum samples of BC patients had elevated levels of acetate,acetone,hypoxanthine,trimethylamine N-oxide(TMAO),glutamate,lactate,phenylalanine,and ornithine.Conversely,there were decreased levels of carnitine,choline,betaine,aspartate,threonine,2-hydroxybutyrate,2-aminobutyrate and histidine when compared with healthy controls.Throughout the CT course,hypoxanthine,glutamate,and aspartate levels increased,while acetone,acetate and TMAO levels decreased.Conclusions:The results of our study confirm perturbations in several metabolic pathways in the serum samples of BC patients,including glycolysis,fatty acid,purine,and amino acid metabolism.Additionally,TMAO may contribute to BC development by fostering a pro-inflammatory and oxidative stress state.Furthermore,monitoring these metabolites could serve as a valuable tool for predicting treatment response.To the best of our knowledge,no metabolomic studies have assessed BC patients undergoing CT with longitudinal monitoring to identify changes in the metabolic profile induced by treatment.展开更多
Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damag...Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.展开更多
文摘Objectives:To date,predictive and prognostic biomarkers for Bladder Cancer(BC)remain lacking.Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification.The primary objective of this study is to characterize the serum metabolic profile of BC patients undergoing platinumbased chemotherapy(Pt-CT)to identify potential biomarkers.Methods:In this pilot study,we investigated the metabolomic profiles of 14 BC patients undergoing Pt-CT in different settings.We compared their baseline profiles with those of healthy controls and tracked key metabolites throughout chemotherapy cycles.Metabolomics profiling was conducted using nuclear magnetic resonance(NMR)spectroscopy.All experiments were performed on a Bruker Avance™600 spectrometer.Results:Serum samples of BC patients had elevated levels of acetate,acetone,hypoxanthine,trimethylamine N-oxide(TMAO),glutamate,lactate,phenylalanine,and ornithine.Conversely,there were decreased levels of carnitine,choline,betaine,aspartate,threonine,2-hydroxybutyrate,2-aminobutyrate and histidine when compared with healthy controls.Throughout the CT course,hypoxanthine,glutamate,and aspartate levels increased,while acetone,acetate and TMAO levels decreased.Conclusions:The results of our study confirm perturbations in several metabolic pathways in the serum samples of BC patients,including glycolysis,fatty acid,purine,and amino acid metabolism.Additionally,TMAO may contribute to BC development by fostering a pro-inflammatory and oxidative stress state.Furthermore,monitoring these metabolites could serve as a valuable tool for predicting treatment response.To the best of our knowledge,no metabolomic studies have assessed BC patients undergoing CT with longitudinal monitoring to identify changes in the metabolic profile induced by treatment.
文摘Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.
