Bile acid distributions, sex-specificity, and prognosis in colorectal cancer

Yuping Cai, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, 06510, USA.Follow
Xinyi Shen, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, 06510, USA.Follow
Lingeng Lu, Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, 06510, USA.Follow
Hong Yan, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, 06510, USA.Follow
Huang Huang, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, 06510, USA.Follow
Patricia Gaule, Department of Pathology, Yale University School of Medicine, New Haven, CT, 06510, USA.
Engjel Muca, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Follow
Casey M. Theriot, North Caroline State University, Raleigh, NC, USA.
Zahra Rattray, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.Follow
Nicholas J. Rattray, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.Follow
Jun Lu, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, 06520, USA.Follow
Nita Ahuja, Department of Pathology, Yale University School of Medicine, New Haven, CT, 06510, USA.Follow
Yawei Zhang, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, 06510, USA.Follow
Philip B. Paty, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Follow
Sajid A. Khan, Department of Surgery, Division of Surgical Oncology, Yale University School of Medicine, New Haven, CT, 06510, USA. sajid.khan@yale.edu.Follow
Caroline H. Johnson, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, 06510, USA. caroline.johnson@yale.edu.Follow

Document Type

Article

Publication Title

Biology of sex differences

Abstract

BACKGROUND: Bile acids are known to be genotoxic and contribute to colorectal cancer (CRC). However, the link between CRC tumor bile acids to tumor location, patient sex, microbiome, immune-regulatory cells, and prognosis is not clear. METHODS: We conducted bile acid analysis using targeted liquid chromatography-mass spectrometry (LC-MS) on tumor tissues from CRC patients (n = 228) with survival analysis. We performed quantitative immunofluorescence (QIF) on tumors to examine immune cells. RESULTS: Twelve of the bile acids were significantly higher in right-sided colon tumors compared to left-sided colon tumors. Furthermore, in male patients, right-sided colon tumors had elevated secondary bile acids (deoxycholic acid, lithocholic acid, ursodeoxycholic acid) compared to left-sided colon tumors, but this difference between tumors by location was not observed in females. A high ratio of glycoursodeoxycholic to ursodeoxycholic was associated with 5-year overall survival (HR = 3.76, 95% CI = 1.17 to 12.1, P = 0.026), and a high ratio of glycochenodeoxycholic acid to chenodeoxycholic acid was associated with 5-year recurrence-free survival (HR = 3.61, 95% CI = 1.10 to 11.84, P = 0.034). We also show correlation between these bile acids and FoxP3 + T regulatory cells. CONCLUSIONS: This study revealed that the distribution of bile acid abundances in colon cancer patients is tumor location-, age- and sex-specific, and are linked to patient prognosis. This study provides new implications for targeting bile acid metabolism, microbiome, and immune responses for colon cancer patients by taking into account primary tumor location and sex.

First Page

61

DOI

10.1186/s13293-022-00473-9

Publication Date

10-23-2022

Identifier

36274154 (pubmed); PMC9590160 (pmc); 10.1186/s13293-022-00473-9 (doi); 10.1186/s13293-022-00473-9 (pii)

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