Exploration of the proteomic landscape of small extracellular vesicles in serum as biomarkers for early detection of colorectal neoplasia
學年 110
學期 1
出版（發表）日期 2021-09-13
作品名稱 Exploration of the proteomic landscape of small extracellular vesicles in serum as biomarkers for early detection of colorectal neoplasia
作品名稱（其他語言）
著者 Li-Chun Chang; Yi-Chiung Hsu; Han-Mo Chiu; Koji Ueda; Ming-Shiang Wu; Chiun-How Kao; Tang-Long Shen
單位
出版者
著錄名稱、卷期、頁數 Frontiers in Oncology 11, 732743
摘要 Background: Patient 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 Methods: We 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. Results: The 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. Conclusion: Patients 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.
關鍵字 colorectal cancer;blood test;small extracellular vesicle;proteome, biomarker
語言 en
ISSN 2234-943X
期刊性質 國外
收錄於 SCI
產學合作
通訊作者 Chiun-How Kao, Tang-Long Shen
審稿制度 是
國別 CHE
公開徵稿
出版型式 ,電子版
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