Mitochondria are abundant organelles containing their own genome and involved in cellular energy production. Their role in various pathological situations such as cardiovascular disease, diabetes, nephropathy, neurodegenerative diseases or cancer has been widely described. Here we tested the role of mitochondrial DNA as a prognostic tool using different matrices: plasma, whole blood and tissue samples from patients with stage IV cancer.
A two-color panel for crystal digital PCR was designed. The first probe was localized on the mitochondrial NADH-Ubiquinone Oxidoreductase Chain 1 (MT-ND1) gene. The second probe was focused on the centromeric region of chromosome 17 (CEP17). Then, a MT-ND1/CEP17 copy number ratio (MCR) was calculated. Three different matrices were evaluated. 96 plasma samples were obtained from patients with stage IV non small cell lung cancers, 110 whole blood samples from different stage IV cancers (20 (18.2%) lung, 19 (17.3%) colon, 18 (16.4%) prostate, 17 (15.4%) urothelial and pancreatic, 10 (9.1%) gastric and 9 (8.2%) cholangiocarcinoma) and 99 metastatic tissue samples (21 (21.2%) lung, 17 (17.2%) prostate, colon and pancreas, 12 (12.1%) urothelial, 8 (8.1%) cholangiocarcinoma and 7 (7.0%) gastric cancer).
Mean of MCR was variable between matrices: 19.9 (IQR: 9.0-23.5) for plasma samples, 94.5 (IQR: 78.5-108.9) for whole blood and 250.3 (IQR: 146.8-306.5) for metastatic tissues. Of note MCR also varied by metastatic site, with higher mean levels in liver metastases than in lung and lymph node metastases (330.3, 202.5, 170.1 respectively, p-value<0.001). MCR may be a useful prognostic tool for plasma and whole blood matrices, as patients with higher MCR had significantly longer median survival times compared to patients with lower MCR (HR = 3.71, 95% CI = 1.56-8.81, p=0.0029 and HR = 2.14, 95% CI = 1.08-4.25, p=0.029 for plasma and whole blood respectively). As the MCR is metastatic site-dependent, the prognostic value was not observed for tissue samples.
Our study reveals that MCR may be a useful prognostic biomarker for metastatic cancer in plasma or whole blood matrices but not in metastatic tissue.
The authors.
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All authors have declared no conflicts of interest.