TY - JOUR
T1 - Survival Disparity and the Unique Genomic and Microbiome Profiles of Colon Cancer in Appalachian Kentucky
AU - McDonald, Hannah G.
AU - Reagan, Anna M.
AU - Faisal, Abu Saleh Mosa
AU - Goettl, Ryan
AU - Wang, Chi
AU - Hoyd, Rebecca
AU - Spakowicz, Daniel
AU - Evers, B. Mark
AU - Kim, Joseph
AU - Bhakta, Avinash S.
N1 - Publisher Copyright:
Copyright © 2025 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.
PY - 2025/4/1
Y1 - 2025/4/1
N2 - BACKGROUND: Colon 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 DESIGN: This 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. RESULTS: The 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). CONCLUSIONS: This 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.
AB - BACKGROUND: Colon 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 DESIGN: This 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. RESULTS: The 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). CONCLUSIONS: This 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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U2 - 10.1097/XCS.0000000000001299
DO - 10.1097/XCS.0000000000001299
M3 - Article
C2 - 39868697
AN - SCOPUS:105001679984
SN - 1072-7515
VL - 240
SP - 612
EP - 624
JO - Journal of the American College of Surgeons
JF - Journal of the American College of Surgeons
IS - 4
ER -
