Exploration of the Proteomic Landscape of Small Extracellular Vesicles in Serum as Biomarkers for Early Detection of Colorectal Neoplasia
BackgroundPatient participation in colorectal cancer (CRC) screening via a stool test and colonoscopy is suboptimal, but participation can be improved by the development of a blood test. However, the suboptimal detection abilities of blood tests for advanced neoplasia, including advanced adenoma (AA...
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doaj-e78246e72f3842fbac0e5d9f624ccad22021-09-13T05:20:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.732743732743Exploration of the Proteomic Landscape of Small Extracellular Vesicles in Serum as Biomarkers for Early Detection of Colorectal NeoplasiaLi-Chun Chang0Li-Chun Chang1Yi-Chiung Hsu2Han-Mo Chiu3Han-Mo Chiu4Koji Ueda5Ming-Shiang Wu6Chiun-How Kao7Tang-Long Shen8Tang-Long Shen9Tang-Long Shen10Department of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanHealth Management Center, National Taiwan University Hospital, Taipei, TaiwanDepartment of Biomedical Science and Engineering, National Central University, Taoyuan, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanHealth Management Center, National Taiwan University Hospital, Taipei, TaiwanCancer Precision Medicine Center, Japanese Foundation of Cancer Research, Tokyo, JapanDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanDepartment of Statistics, Tamkang University, New Taipei City, TaiwanDepartment of Plant Pathology and Microbiology, National Taiwan University, Taipei, TaiwanCenter for Biotechnology, National Taiwan University, Taipei, TaiwanGenome and Systems Biology Degree Program, National Taiwan University, Taipei, TaiwanBackgroundPatient participation in colorectal cancer (CRC) screening via a stool test and colonoscopy is suboptimal, but participation can be improved by the development of a blood test. However, the suboptimal detection abilities of blood tests for advanced neoplasia, including advanced adenoma (AA) and CRC, limit their application. We aimed to investigate the proteomic landscape of small extracellular vesicles (sEVs) from the serum of patients with colorectal neoplasia and identify specific sEV proteins that could serve as biomarkers for early diagnosis.Materials and MethodsWe enrolled 100 patients including 13 healthy subjects, 12 non-AAs, 13 AAs, and 16 stage-I, 15 stage-II, 16 stage-III, and 15 stage-IV CRCs. These patients were classified as normal control, early neoplasia, and advanced neoplasia. The sEV proteome was explored by liquid chromatography-tandem mass spectrometry. Generalized association plots were used to integrate the clustering methods, visualize the data matrix, and analyze the relationship. The specific sEV biomarkers were identified by a decision tree via Orange3 software. Functional enrichment analysis was conducted by using the Ingenuity Pathway Analysis platform.ResultsThe sEV protein matrix was identified from the serum of 100 patients and contained 3353 proteins, of which 1921 proteins from 98 patients were finally analyzed. Compared with the normal control, subjects with early and advanced neoplasia exhibited a distinct proteomic distribution in the data matrix plot. Six sEV proteins were identified, namely, GCLM, KEL, APOF, CFB, PDE5A, and ATIC, which properly distinguished normal control, early neoplasia, and advanced neoplasia patients from each other. Functional enrichment analysis revealed that APOF+ and CFB+ sEV associated with clathrin-mediated endocytosis signaling and the complement system, which have critical implications for CRC carcinogenesis.ConclusionPatients with colorectal neoplasia had a distinct sEV proteome expression pattern in serum compared with those patients who were healthy and did not have neoplasms. Moreover, the six identified specific sEV proteins had the potential to discriminate colorectal neoplasia between early-stage and advanced neoplasia. Collectively, our study provided a six-sEV protein biomarker panel for CRC diagnosis at early or advanced stages. Furthermore, the implication of the sEV proteome in CRC carcinogenesis via specific signaling pathways was explored.https://www.frontiersin.org/articles/10.3389/fonc.2021.732743/fullcolorectal cancerblood testsmall extracellular vesicleproteomebiomarker |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li-Chun Chang Li-Chun Chang Yi-Chiung Hsu Han-Mo Chiu Han-Mo Chiu Koji Ueda Ming-Shiang Wu Chiun-How Kao Tang-Long Shen Tang-Long Shen Tang-Long Shen |
spellingShingle |
Li-Chun Chang Li-Chun Chang Yi-Chiung Hsu Han-Mo Chiu Han-Mo Chiu Koji Ueda Ming-Shiang Wu Chiun-How Kao Tang-Long Shen Tang-Long Shen Tang-Long Shen Exploration of the Proteomic Landscape of Small Extracellular Vesicles in Serum as Biomarkers for Early Detection of Colorectal Neoplasia Frontiers in Oncology colorectal cancer blood test small extracellular vesicle proteome biomarker |
author_facet |
Li-Chun Chang Li-Chun Chang Yi-Chiung Hsu Han-Mo Chiu Han-Mo Chiu Koji Ueda Ming-Shiang Wu Chiun-How Kao Tang-Long Shen Tang-Long Shen Tang-Long Shen |
author_sort |
Li-Chun Chang |
title |
Exploration of the Proteomic Landscape of Small Extracellular Vesicles in Serum as Biomarkers for Early Detection of Colorectal Neoplasia |
title_short |
Exploration of the Proteomic Landscape of Small Extracellular Vesicles in Serum as Biomarkers for Early Detection of Colorectal Neoplasia |
title_full |
Exploration of the Proteomic Landscape of Small Extracellular Vesicles in Serum as Biomarkers for Early Detection of Colorectal Neoplasia |
title_fullStr |
Exploration of the Proteomic Landscape of Small Extracellular Vesicles in Serum as Biomarkers for Early Detection of Colorectal Neoplasia |
title_full_unstemmed |
Exploration of the Proteomic Landscape of Small Extracellular Vesicles in Serum as Biomarkers for Early Detection of Colorectal Neoplasia |
title_sort |
exploration of the proteomic landscape of small extracellular vesicles in serum as biomarkers for early detection of colorectal neoplasia |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-09-01 |
description |
BackgroundPatient participation in colorectal cancer (CRC) screening via a stool test and colonoscopy is suboptimal, but participation can be improved by the development of a blood test. However, the suboptimal detection abilities of blood tests for advanced neoplasia, including advanced adenoma (AA) and CRC, limit their application. We aimed to investigate the proteomic landscape of small extracellular vesicles (sEVs) from the serum of patients with colorectal neoplasia and identify specific sEV proteins that could serve as biomarkers for early diagnosis.Materials and MethodsWe enrolled 100 patients including 13 healthy subjects, 12 non-AAs, 13 AAs, and 16 stage-I, 15 stage-II, 16 stage-III, and 15 stage-IV CRCs. These patients were classified as normal control, early neoplasia, and advanced neoplasia. The sEV proteome was explored by liquid chromatography-tandem mass spectrometry. Generalized association plots were used to integrate the clustering methods, visualize the data matrix, and analyze the relationship. The specific sEV biomarkers were identified by a decision tree via Orange3 software. Functional enrichment analysis was conducted by using the Ingenuity Pathway Analysis platform.ResultsThe sEV protein matrix was identified from the serum of 100 patients and contained 3353 proteins, of which 1921 proteins from 98 patients were finally analyzed. Compared with the normal control, subjects with early and advanced neoplasia exhibited a distinct proteomic distribution in the data matrix plot. Six sEV proteins were identified, namely, GCLM, KEL, APOF, CFB, PDE5A, and ATIC, which properly distinguished normal control, early neoplasia, and advanced neoplasia patients from each other. Functional enrichment analysis revealed that APOF+ and CFB+ sEV associated with clathrin-mediated endocytosis signaling and the complement system, which have critical implications for CRC carcinogenesis.ConclusionPatients with colorectal neoplasia had a distinct sEV proteome expression pattern in serum compared with those patients who were healthy and did not have neoplasms. Moreover, the six identified specific sEV proteins had the potential to discriminate colorectal neoplasia between early-stage and advanced neoplasia. Collectively, our study provided a six-sEV protein biomarker panel for CRC diagnosis at early or advanced stages. Furthermore, the implication of the sEV proteome in CRC carcinogenesis via specific signaling pathways was explored. |
topic |
colorectal cancer blood test small extracellular vesicle proteome biomarker |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.732743/full |
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