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一项基于蛋白质芯片的血清蛋白质组学研究揭示了结直肠癌中独特的自身抗体特征。

A protein microarray-based serum proteomic investigation reveals distinct autoantibody signature in colorectal cancer.

作者信息

Barpanda Abhilash, Tuckley Chaitanya, Ray Arka, Banerjee Arghya, Duttagupta Siddhartha P, Kantharia Chetan, Srivastava Sanjeeva

机构信息

Centre for Research in Nanotechnology & Science (CRNTS), Indian Institute of Technology Bombay, Mumbai, India.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.

出版信息

Proteomics Clin Appl. 2023 Mar;17(2):e2200062. doi: 10.1002/prca.202200062. Epub 2022 Nov 29.

Abstract

PURPOSE

Colorectal cancer (CRC) has been reported as the second leading cause of cancer death worldwide. The 5-year annual survival is around 50%, mainly due to late diagnosis, striking necessity for early detection. This study aims to identify autoantibody in patients' sera for early screening of cancer.

EXPERIMENTAL DESIGN

The study used a high-density human proteome array with approximately 17,000 recombinant proteins. Screening of sera from healthy individuals, CRC from Indian origin, and CRC from middle-east Asia origin were performed. Bio-statistical analysis was performed to identify significant autoantibodies altered. Pathway analysis was performed to explore the underlying mechanism of the disease.

RESULTS

The comprehensive proteomic analysis revealed dysregulation of 15 panels of proteins including CORO7, KCNAB1, WRAP53, NDUFS6, KRT30, and COLGALT2. Further biological pathway analysis for the top dysregulated autoantigenic proteins revealed perturbation in important biological pathways such as ECM degradation and cytoskeletal remodeling etc. CONCLUSIONS AND CLINICAL RELEVANCE: The generation of an autoimmune response against cancer-linked pathways could be linked to the screening of the disease. The process of immune surveillance can be detected at an early stage of cancer. Moreover, AAbs can be easily extracted from blood serum through the least invasive test for disease screening.

摘要

目的

据报道,结直肠癌(CRC)是全球癌症死亡的第二大主要原因。其5年生存率约为50%,主要归因于诊断较晚,因此早期检测极为必要。本研究旨在鉴定患者血清中的自身抗体以进行癌症的早期筛查。

实验设计

该研究使用了包含约17,000种重组蛋白的高密度人类蛋白质组芯片。对健康个体、印度裔CRC患者以及中东裔CRC患者的血清进行了筛查。进行生物统计学分析以鉴定发生显著改变的自身抗体。进行通路分析以探究该疾病的潜在机制。

结果

全面的蛋白质组学分析揭示了包括CORO7、KCNAB1、WRAP53、NDUFS6、KRT30和COLGALT2在内的15组蛋白质的失调。对失调最严重的自身抗原性蛋白质进行的进一步生物学通路分析显示,重要的生物学通路如细胞外基质降解和细胞骨架重塑等受到了干扰。结论与临床意义:针对癌症相关通路产生的自身免疫反应可能与该疾病的筛查相关。免疫监视过程可在癌症早期被检测到。此外,通过侵入性最小的检测从血清中轻松提取自身抗体可用于疾病筛查。

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