Molecular medicine (Cambridge, Mass.) · 2025
Dysregulated mitochondrial homeostasis and DNA repair in the progression from colon adenoma to cancer.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
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История · было → стало
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Danesova Natalie, Horak Josef, Valickova Anna, Gil-Korilis Adrian, Ergui-Arbizu Jorge, Palek Richard, Bruha Jan, Levy Miroslav, Skrobanek Pavel, Kral Jan, Jungwirth Jiri, Neuzil Jiri, Vymetalkova Veronika, Vodicka Pavel, Vodenkova Sona, Tomasova Kristyna
Аннотация
BACKGROUND: While nuclear DNA (nDNA) damage and alterations in nDNA repair are known to play a role in colon cancer (CC), there is insufficient research investigating these processes in mitochondrial DNA (mtDNA).
METHODS: This study investigates mtDNA changes in CC, focusing on mitochondrial DNA copy number (mtDNA-CN) variations, mtDNA damage, and the expression and mutation status of DNA repair genes. Three cohorts were analyzed: healthy controls, colon adenoma patients, and CC patients, divided into a pilot and a validation set.
RESULTS: Our findings revealed that mtDNA-CN was elevated in colon adenomas compared to adenoma-adjacent mucosa (FDR = 0.04), healthy mucosa (FDR = 0.005), and tumor-adjacent mucosa (FDR = 0.005). Moreover, mtDNA-CN was elevated in adenoma-adjacent mucosa compared to healthy mucosa (FDR = 0.04). MtDNA damage was greater in tumor-adjacent mucosa compared to tumor tissue in both the pilot and validation sets (FDR = 0.031 and FDR = 2.06e-05, respectively). Additionally, we identified novel DNA repair genes associated with mtDNA damage, predominantly upregulated in adenoma and tumor tissues compared to healthy colon tissues.
CONCLUSIONS: To conclude, this study highlights the importance of mtDNA alterations in CC development and identifies potential mtDNA biomarkers.
METHODS: This study investigates mtDNA changes in CC, focusing on mitochondrial DNA copy number (mtDNA-CN) variations, mtDNA damage, and the expression and mutation status of DNA repair genes. Three cohorts were analyzed: healthy controls, colon adenoma patients, and CC patients, divided into a pilot and a validation set.
RESULTS: Our findings revealed that mtDNA-CN was elevated in colon adenomas compared to adenoma-adjacent mucosa (FDR = 0.04), healthy mucosa (FDR = 0.005), and tumor-adjacent mucosa (FDR = 0.005). Moreover, mtDNA-CN was elevated in adenoma-adjacent mucosa compared to healthy mucosa (FDR = 0.04). MtDNA damage was greater in tumor-adjacent mucosa compared to tumor tissue in both the pilot and validation sets (FDR = 0.031 and FDR = 2.06e-05, respectively). Additionally, we identified novel DNA repair genes associated with mtDNA damage, predominantly upregulated in adenoma and tumor tissues compared to healthy colon tissues.
CONCLUSIONS: To conclude, this study highlights the importance of mtDNA alterations in CC development and identifies potential mtDNA biomarkers.