UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment

Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal th...

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Main Authors: Zhan Wang, Xiaoyan Liu, Wenda Wang, Jiyu Xu, Haidan Sun, Jing Wei, Yuncui Yu, Yang Zhao, Xu Wang, Zhangcheng Liao, Wei Sun, Lulu Jia, Yushi Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2023.1000248/full
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author Zhan Wang
Xiaoyan Liu
Wenda Wang
Jiyu Xu
Haidan Sun
Jing Wei
Yuncui Yu
Yang Zhao
Xu Wang
Zhangcheng Liao
Wei Sun
Lulu Jia
Yushi Zhang
author_facet Zhan Wang
Xiaoyan Liu
Wenda Wang
Jiyu Xu
Haidan Sun
Jing Wei
Yuncui Yu
Yang Zhao
Xu Wang
Zhangcheng Liao
Wei Sun
Lulu Jia
Yushi Zhang
author_sort Zhan Wang
collection DOAJ
description Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis.Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms.Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism.Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.
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spelling doaj.art-8ba9d0087aa44c79be1f7a5b6cc109db2023-02-20T07:02:37ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-02-011010.3389/fmolb.2023.10002481000248UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatmentZhan Wang0Xiaoyan Liu1Wenda Wang2Jiyu Xu3Haidan Sun4Jing Wei5Yuncui Yu6Yang Zhao7Xu Wang8Zhangcheng Liao9Wei Sun10Lulu Jia11Yushi Zhang12Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaSchool of Basic Medical College, Core facility of instrument, Institution of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaSchool of Basic Medical College, Core facility of instrument, Institution of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Basic Medical College, Core facility of instrument, Institution of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaClinical Research Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaClinical Research Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaSchool of Basic Medical College, Core facility of instrument, Institution of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaClinical Research Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaAim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis.Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms.Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism.Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1000248/fullUPLC-MSproteomicsmetabolomicstuberous sclerosis complexeverolimus
spellingShingle Zhan Wang
Xiaoyan Liu
Wenda Wang
Jiyu Xu
Haidan Sun
Jing Wei
Yuncui Yu
Yang Zhao
Xu Wang
Zhangcheng Liao
Wei Sun
Lulu Jia
Yushi Zhang
UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment
Frontiers in Molecular Biosciences
UPLC-MS
proteomics
metabolomics
tuberous sclerosis complex
everolimus
title UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment
title_full UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment
title_fullStr UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment
title_full_unstemmed UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment
title_short UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment
title_sort uplc ms based integrated plasma proteomic and metabolomic profiling of tsc raml and its relationship with everolimus treatment
topic UPLC-MS
proteomics
metabolomics
tuberous sclerosis complex
everolimus
url https://www.frontiersin.org/articles/10.3389/fmolb.2023.1000248/full
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