ArticleJournal of the American College of Surgeons2025
Survival Disparity and the Unique Genomic and Microbiome Profiles of Colon Cancer in Appalachian Kentucky.
Article in Journal of the American College of Surgeons, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundColon cancer is a leading cause of mortality in Appalachian Kentucky. Studies suggest that the microbiome may influence cancer outcomes. We investigate differential gene expression, the tumor microbiome, and their association as potential drivers of disparities in colon cancer outcomes. STUDY
designThis study analyzed patients diagnosed with colon adenocarcinoma between 2010 and 2023. Demographic data were extracted from Kentucky Cancer Registry. Somatic mutations and significantly mutated genes were identified using Fisher's exact t -test. RNASeq data were processed for gene expression analysis and Holm-Bonferroni method was used to adjust p values for multiple comparisons. The STAR aligner (exotic), v2.1 pipeline, and KrakenUniq database were used to classify microbes in human samples. The R package (exotic) was then used to decontaminate the results.
resultsThe final cohort included 2,276 patients, 321 of which had available somatic mutation sequencing data. Demographic differences between Appalachian and non-Appalachian patients included marital status (p = 0.0005), race (p < 0.0001), insurance status (p = 0.0005), BMI (p = 0.001), type 2 diabetes (p < 0.0001), and Charlson Comorbidity Index (p = 0.03). There was no difference in gene mutation frequency. There was differential expression of 228 genes. Differential abundance analysis revealed differences in 381 bacterial species. Importantly, 3 microbiota significantly correlated with survival disparities between Appalachian and non-Appalachian patients: Clostridium cadaveris (adjusted p = 0.009), Ligilactobacillus salivarius (adjusted p = 0.048), and Sutterella wadsworthensis (adjusted p = 0.009).
conclusionsThis is the first report of the distinct tumor microbiome in Appalachian Kentucky and its impact on survival. Further studies are needed to better characterize the unique tumor and gut microbiome of Appalachian patients with colon cancer.
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