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Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer

BACKGROUND: The surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive...

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Autores principales: Li, Lingling, Liu, Hui, Li, Yan, Guo, Chunmei, Wang, Bing, Shen, Dan, Zhang, Qiao, Ding, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994365/
https://www.ncbi.nlm.nih.gov/pubmed/35397555
http://dx.doi.org/10.1186/s12953-022-00188-0
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author Li, Lingling
Liu, Hui
Li, Yan
Guo, Chunmei
Wang, Bing
Shen, Dan
Zhang, Qiao
Ding, Chen
author_facet Li, Lingling
Liu, Hui
Li, Yan
Guo, Chunmei
Wang, Bing
Shen, Dan
Zhang, Qiao
Ding, Chen
author_sort Li, Lingling
collection PubMed
description BACKGROUND: The surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer. METHODS: In this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC). RESULTS: We identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic. CONCLUSION: We disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12953-022-00188-0.
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spelling pubmed-89943652022-04-10 Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer Li, Lingling Liu, Hui Li, Yan Guo, Chunmei Wang, Bing Shen, Dan Zhang, Qiao Ding, Chen Proteome Sci Research BACKGROUND: The surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer. METHODS: In this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC). RESULTS: We identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic. CONCLUSION: We disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12953-022-00188-0. BioMed Central 2022-04-09 /pmc/articles/PMC8994365/ /pubmed/35397555 http://dx.doi.org/10.1186/s12953-022-00188-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Lingling
Liu, Hui
Li, Yan
Guo, Chunmei
Wang, Bing
Shen, Dan
Zhang, Qiao
Ding, Chen
Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer
title Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer
title_full Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer
title_fullStr Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer
title_full_unstemmed Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer
title_short Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer
title_sort integrative proteomic characterization of trace ffpe samples in early-stage gastrointestinal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994365/
https://www.ncbi.nlm.nih.gov/pubmed/35397555
http://dx.doi.org/10.1186/s12953-022-00188-0
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