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通过生物信息学分析和机器学习鉴定结直肠息肉和代谢相关脂肪性肝病(MASH)诊断的生物标志物。

Identification of biomarkers for the diagnosis in colorectal polyps and metabolic dysfunction-associated steatohepatitis (MASH) by bioinformatics analysis and machine learning.

机构信息

Department of Gastroenterology and Hepatology, China-Japan Union Hospital, Jilin University, Changchun, 130033, China.

出版信息

Sci Rep. 2024 Nov 27;14(1):29463. doi: 10.1038/s41598-024-81120-8.

DOI:10.1038/s41598-024-81120-8
PMID:39604470
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11603146/
Abstract

Colorectal polyps are precursors of colorectal cancer. Metabolic dysfunction associated steatohepatitis (MASH) is one of metabolic dysfunction associated fatty liver disease (MAFLD) phenotypic manifestations. Much evidence has suggested an association between MASH and polyps. This study investigated the biomarkers of MASH and colorectal polyps, and the prediction of targeted drugs using an integrated bioinformatics analysis method. Differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were performed on GSE89632 and GSE41258 datasets, 49 shared genes revealed after intersection. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses depicted they were mainly enriched in apoptosis, proliferation and infection pathways. Machine learning algorithms identified S100P, FOXO1, and LPAR1 were biomarkers for colorectal polyps and MASH, ROC curve and violin plot showed ideal AUC and stable expression patterns in both the discovery and validation sets. GSEA analysis showed significant enrichment of bile acid and fatty acid pathways when grouped by the expression levels of the three candidate biomarkers. Immune infiltration analysis showed a significant infiltration of M0 macrophages and Treg cells in the colorectal polyps group. A total of 9 small molecule compounds were considered as potential chemoprevention agents in MASH and colorectal polyps by using the CMap website. Using integrated bioinformatics analysis, the molecular mechanism between MASH and colorectal polyps has been further explored.

摘要

结直肠息肉是结直肠癌的前体。代谢相关脂肪性肝炎(MASH)是代谢相关脂肪性肝病(MAFLD)的一种表型表现。大量证据表明 MASH 与息肉之间存在关联。本研究通过综合生物信息学分析方法,研究了 MASH 和结直肠息肉的生物标志物,以及靶向药物的预测。对 GSE89632 和 GSE41258 数据集进行差异表达基因(DEG)分析和加权基因共表达网络分析(WGCNA),经交集后得到 49 个共有基因。GO 和 KEGG 富集分析表明,它们主要富集在凋亡、增殖和感染途径中。机器学习算法鉴定出 S100P、FOXO1 和 LPAR1 是结直肠息肉和 MASH 的生物标志物,ROC 曲线和小提琴图显示在发现集和验证集中均具有理想的 AUC 和稳定的表达模式。GSEA 分析表明,当按三个候选生物标志物的表达水平分组时,胆汁酸和脂肪酸途径显著富集。免疫浸润分析显示,M0 巨噬细胞和 Treg 细胞在结直肠息肉组中大量浸润。通过 CMap 网站,共筛选出 9 种小分子化合物作为 MASH 和结直肠息肉的潜在化学预防剂。通过综合生物信息学分析,进一步探讨了 MASH 和结直肠息肉之间的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/3e7498428320/41598_2024_81120_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/9f6419f39485/41598_2024_81120_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/418052a2119c/41598_2024_81120_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/78a2789ffb89/41598_2024_81120_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/3ffc8b1085c4/41598_2024_81120_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/3590b731f4a5/41598_2024_81120_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/6e7e969fe4a0/41598_2024_81120_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/8e152558ca0f/41598_2024_81120_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/6585799f6a6c/41598_2024_81120_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/3e7498428320/41598_2024_81120_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/9f6419f39485/41598_2024_81120_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/418052a2119c/41598_2024_81120_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/78a2789ffb89/41598_2024_81120_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/3ffc8b1085c4/41598_2024_81120_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/3590b731f4a5/41598_2024_81120_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/6e7e969fe4a0/41598_2024_81120_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/8e152558ca0f/41598_2024_81120_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/6585799f6a6c/41598_2024_81120_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/11603146/3e7498428320/41598_2024_81120_Fig9_HTML.jpg

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