Low
mitochondrial DNA (
mtDNA) copy number in
tumors has been associated with worse prognosis in
colorectal cancer (CRC). This study further deciphers the role of
mtDNA copy number in CRC by comparing
mtDNA copy number between healthy,
adenoma and
carcinoma tissue, by investigating its association according to several clinicopathological characteristics in CRC, and by relating it to CRC-specific survival in CRC patients. A hospital-based series of samples including
cancer,
adenoma and adjacent histologically normal tissue from primary CRC patients (n = 56) and recurrent CRC (n = 16) was studied as well as colon mucosa samples from healthy subjects (n = 76). Furthermore,
mtDNA copy number was assessed in
carcinomas of 693 CRC cases identified from the population-based Netherlands Cohort Study (NLCS).
MtDNA copy number was significantly lower in
carcinoma tissue (P = 0.011) and adjacent tissue (P < 0.001) compared to earlier resected
adenoma tissue and in primary CRC tissue compared to recurrent CRC tissue (P = 0.011). Within both study populations,
mtDNA copy number was significantly lower in mutated BRAF (P = 0.027 and P = 0.006) and in microsatellite unstable (MSI)
tumors (P = 0.033 and P < 0.001) and higher in KRAS mutated
tumors (P = 0.004). Furthermore, the association between
mtDNA and survival seemed to follow an inverse U-shape with the highest HR observed in the second quintile of
mtDNA copy number (HR = 1.70, 95% CI = 1.18, 2.44) compared to the first quintile. These results might reflect an association of
mtDNA copy number with various malignant processes in
cancer cells and warrants further research on
tumor energy metabolism in CRC prognosis.