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Gut Microbiota Mediate Periampullary Cancer Through Extracellular Matrix Proteins: A Causal Relationship Study
Zeying Cheng1,2, Liqian Du1,2, Hongxia Zhang3
1School of Pharmacy, Lanzhou University, Lanzhou, China.
Abstract:
Recent studies have reported that gut microbiota may play a role in the occurrence and development of digestive system cancers. Periampullary cancer is a relatively rare digestive system cancer which lacks effective targeted therapy and specific drugs. The purpose of this study is to elucidate the relationship between periampullary cancer and gut microbiota. This work collected public genome-wide association study (GWAS) data from 211 gut microbial taxa and three types of cancer related to periampullary cancer, which were used for two-sample Mendelian randomisation (MR) analysis. Based on the analysis of differentially expressed genes between periampullary cancer and adjacent normal tissue, extracellular matrix proteins were selected for further multivariable MR analysis. Finally, the Connectivity Map was used to screen potential therapeutic drugs for periampullary cancer. Two-sample MR results confirmed that nine microbial taxa, Tyzzerella, Alloprevotella, Holdemania, LachnospiraceaeUCG010, Terrisporobacter, Alistipes, Rikenellaceae, Anaerofilum and Dialister, were associated with periampullary cancer risk. Multivariable MR discovered extracellular matrix-related proteins [Collagen alpha-1(I) chain, Laminin, Fibronectin and Mucin] that may play a role in the association between gut microbiota and periampullary cancer. Finally, the Connectivity Map identified 27 potential candidate drugs. This study can provide theoretical basis for future prevention and diagnostic research on this rare cancer.
Insights
Gut microbes influence periampullary cancer risk, with nine taxa linked to its development. This research identifies potential therapeutic drugs and extracellular matrix proteins involved in this rare digestive cancer.
Area of Science:
- Gastroenterology
- Oncology
- Microbiology
- Genetics
Background:
- Gut microbiota dysbiosis is increasingly implicated in digestive system cancers.
- Periampullary cancer is a rare malignancy with limited therapeutic options.
- Understanding the gut microbiome's role is crucial for novel treatment strategies.
Purpose of the Study:
- To investigate the association between gut microbial composition and periampullary cancer risk.
- To identify potential therapeutic targets and drugs for periampullary cancer.
Main Methods:
- Two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data for gut microbial taxa and periampullary cancer.
- Multivariable MR analysis incorporating differentially expressed extracellular matrix proteins.
- Drug screening using the Connectivity Map.
Main Results:
- Nine gut microbial taxa (Tyzzerella, Alloprevotella, Holdemania, LachnospiraceaeUCG010, Terrisporobacter, Alistipes, Rikenellaceae, Anaerofilum, Dialister) were significantly associated with periampullary cancer risk.
- Extracellular matrix proteins, including Collagen alpha-1(I) chain, Laminin, Fibronectin, and Mucin, were identified as potential mediators.
- 27 candidate drugs were identified for potential periampullary cancer therapy.
Conclusions:
- Specific gut microbial taxa are associated with periampullary cancer risk.
- Extracellular matrix proteins may mediate the link between gut microbiota and periampullary cancer.
- This study provides a foundation for developing targeted therapies and diagnostic tools for periampullary cancer.
