Exploring the relationship between anal fistula and colorectal cancer based on Mendelian randomization and bioinformatics

Author:

Liu Yicheng1ORCID,Zhao Wenjun1,Hu Weiye2,Xu Jin1,Zhang Haiyan1,Huang Ting1,Wu Chuang1,Yang Jiajia1,Mao Wenjing1,Yao Xiaobing3,Lu Yafeng4,Wang Qingming14

Affiliation:

1. Department of Anorectal Surgery Shanghai Baoshan Hospital of Intergrated Traditonal Chinese and Western Medicine Shanghai China

2. Department of Liver, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine Shanghai China

3. Department of Gastrointestinal Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine Shanghai China

4. Department of Anorectal Surgery, Shuguang Hospital Shanghai University of Traditional Chinese Medicine Shanghai China

Abstract

AbstractThe association between anal fistula patients and colorectal cancer, as well as the potential pathophysiological mechanisms, remains unclear. To explore the relationship between anal fistula and colorectal cancer and its potential mechanisms. Analysis of GEO and TCGA databases. Disease‐related genes were also referenced from Coremine Medical, GeneCard and OMIM. Core hub genes were identified through protein–protein interaction analysis by intersecting differentially expressed genes from the datasets with disease data. On one hand, a prognostic model was developed using genes and its prognostic role was validated. On the other hand, the optimal diagnostic genes were selected through machine learning. Mendelian randomization (MR) analysis was conducted to explore the potential causal link between anal fistula and colorectal cancer. Thirteen core genes were identified (TMEM121B, PDGFRA, MID2, WNT10B, HOXD13, BARX1, SIX2, MMP1, SNAL1, CDKN2A, ITGB3, TIMP1, CALB2). Functional enrichment analysis revealed that the intersecting genes between anal fistula and colorectal cancer were associated with extracellular matrix components, signalling pathways, cell growth, protein modification, as well as important roles in cellular activities, tissue and organ development, and biological function maintenance. These genes were also involved in pathways related to Wnt signalling and colorectal cancer development. Prognostic analysis and immune infiltration analysis indicated a close relationship between core hub genes and the prognosis and immune infiltration in colorectal cancer. Machine learning showed that core genes played an essential role in the diagnostic differentiation of colorectal cancer. MR results suggested no causal relationship between anal fistula and colorectal cancer. This study identified shared core genes between anal fistula and colorectal cancer, involved in various pathways related to tumour development. These genes play crucial roles in prognosis and diagnosis.

Publisher

Wiley

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