The structural integrity of mitochondrial DNA reveals new molecular perspectives for early diagnosis of colorectal cancer

• Conditions: C18; C20; Malignant neoplasm of colon; Malignant neoplasm of rectum

• Registration Number: DRKS00030257
• Lead Sponsor: Medizinischen Hochschule Brandenburg (MHB) Theodor Fontane, Dezernat für Wissenschaft und Forschung

Brief Summary

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. 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. Predictive models based on different analysis and predictor sets 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-29
• Results First Posted: 2023-03-30
• Study Completion: 2023-03-31
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 81

Inclusion Criteria

1. Healthy subjects (must be available for purchase for research purposes (at Central Biobank GmbH) between the ages of 18 and 90

2. All male and female colorectal cancer patients (> 18 years) are included with the ability to understand and question the relevant patient information with a diagnosis of colorectal cancer who are referred for surgery

3. Patient's willingness to provide blood and tissue samples for scientific analysis as part of the preliminary study

4. A written declaration of consent (for healthy people and patients) must be available

Exclusion Criteria

1. Healthy subjects under 18 years of age

2. Colorectal cancer patients with manifest coronary heart disease, chronic heart failure and peripheral arterial disease

3. Colorectal cancer patients with other tumor diseases

4. Colon cancer patients with advanced renal failure

5. Colon cancer patients with chronic inflammatory diseases

6. Healthy subjects and patients who do not meet the inclusion criteria or who their Withdraw consent to participate in the study

Study & Design

• Study Type: observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The aim of this study is: 1) to analyze total cfDNA concentration in CRC patients with different histopathological stages (UICC I-IV). 2) to address the question whether the integrity index of cfDNA increases in CRC patients as a result of elevated necrotic degradation processes. Therefore, we intended to quantify short and long fragments of cfDNA via qPCR independent from total cfDNA levels by using equal template concentrations for CRC patients and healthy individuals. This approach may help to understand whether previously described diagnostic markers are either increased, decreased or unaltered in blood plasma of CRC patients compared to healthy individuals.