SEARCHCOHORToncology, gastroenterology

cohort·oncology, gastroenterology, clinical trial, observational study·PMC10064655

Quantification of mitochondrial cfDNA reveals new perspectives for early diagnosis of colorectal cancer

BMC Cancer · 5 authors, 3 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This cohort study measured nuclear and mitochondrial cell-free DNA (cfDNA) fragments in plasma from colorectal cancer patients and healthy individuals. It found that total cfDNA levels increased with tumor stage, while mitochondrial cfDNA (MTCO3) fragments were significantly reduced, especially in early stages, suggesting potential for improved early diagnosis.

Full summary

757 CHARS

This observational cohort study analyzed plasma cfDNA from 80 colorectal cancer patients (stratified by UICC stage I-IV) and 50 healthy controls. Using qPCR, researchers quantified total cfDNA and fragments of nuclear (KRAS, Alu) and mitochondrial (MTCO3) markers under two conditions: equal template concentration (ETC) and normalized to total concentration (NTC). Total cfDNA levels were significantly higher in cancer patients and increased with tumor stage. Nuclear long fragment levels and integrity indices were significantly lower in cancer patients under ETC. Mitochondrial cfDNA fragment quantities were strongly reduced in early and late-stage patients under ETC. Diagnostic models based on ETC or NTC predictor sets showed comparable performance.

STUDY TYPE

cohort

SPECIALTY

oncology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10064655

Quantification of mitochondrial cfDNA reveals new perspectives for early diagnosis of colorectal cancer

BMC Cancer

READ THE FULL PAPER

ABSTRACT

Abstract Background To unravel how the integrity of nuclear and mitochondrial circulating cell-free DNA (cfDNA) contributes to its plasma quantity in colorectal cancer (CRC) patients. Methods CfDNA from plasma samples of 80 CRC patients stratified by tumour stage and 50 healthy individuals were extracted. Total cfDNA concentration was determined and equal template concentrations (ETC) were analyzed by quantitative real-time PCR (qPCR) resulting in small and long fragments of KRAS, Alu and MTCO3. The obtained data was also examined relative to the total cfDNA concentration (NTC) and diagnostic accuracy was estimated using receiver operating characteristics. Results Total cfDNA levels were significantly higher in CRC group compared to healthy control and increased with tumour stage. Long nuclear fragment levels were significantly lower in CRC patients in ETC but not NTC condition. The integrity indices of nuclear cfDNA decreased from controls to patients with highly malignant tumor. Mitochondrial cfDNA fragment quantities were strongly reduced in early and late stages of tumor patients and prognostic value was higher in ETC. Predictive models based on either ETC or NTC predictor set showed comparable classification performance. Conclusion Increased blood cfDNA concentration in late UICC stages inversely correlate with nuclear cfDNA integrity index and suggest that necrotic degradation is not a major cause for higher total cfDNA quantity. The diagnostic and prognostic value of MTCO3 is highly significant in early stages of CRC and can be evaluated more comprehensively, using ETC for qPCR analysis. Trial registration The study was registered retrospectively on DRKS, the german register for clinical trials (DRKS00030257, 29/09/2022). Supplementary Information The online version contains supplementary material available at 10.1186/s12885-023-10748-y. Keywords: Colorectal cancer, cfDNA, Tumour marker, Predictive model, Diagnostic accuracy

CITATION EXPORT

Christian Linke, Richard Hunger, Mark Reinwald et al.. Quantification of mitochondrial cfDNA reveals new perspectives for early diagnosis of colorectal cancer. BMC Cancer. (2023). https://doi.org/10.1186/s12885-023-10748-y

AUTHORS

5 · 3 CENTRES

Christian Linke, Richard Hunger, Mark Reinwald, Markus Deckert, René Mantke

1Department of General and Gastrointestinal Surgery, University Hospital Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg, Germany
2Department of Hematology, Oncology and Palliative Medicine, University Hospital Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg, Germany
3Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus – Senftenberg, the Brandenburg Medical School Theodor Fontane and the University of Potsdam, Potsdam, Germany