Mitochondrial DNA Copy Number Variations and Serum Pepsinogen Levels for Risk Assessment in Gastric Cancer

Authors
Mehdi Alikhani 1
Samaneh Saberi 1
Maryam Esmaily 1
Valérie Michel 2
Mohammad Tashakoripour 3
Afshin Abdirad 4
Arezoo Aghakhani 5
Sana Eybpoosh 6
Massoud Vosough 7
Mohammad Ali Mohagheghi 8
Mahmoud Eshagh Hosseini 3
Eliette Touati 2
Marjan Mohammadi 1
1 HPGC Research Group, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
2 Institut Pasteur, Unit of Helicobacter Pathogenesis, CNRS UMR2001, 25-28 Rue du Dr Roux, 75724 Paris Cedex 15, France
3 Gastroenterology Department, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran
4 Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
5 Clinical Research Dept., Pasteur Institute of Iran, Tehran, Iran
6 Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
7 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
8 Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran
10.52547/ibj.25.5.323
Abstract
Background: Variations in mitochondrial DNA copy number (mtDNA-CN) of peripheral blood leukocytes (PBLs), as a potential biomarker for gastric cancer (GC) screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with serum pepsinogen (sPG) I/II ratio, as an established indicator of gastric atrophy. Methods: The study population included GC (n = 53) and non-GC (n = 207) dyspeptic patients. The non-GC group was histologically categorized into CG (n = 104) and NM (n = 103) subgroups. The MtDNA-CN of PBLs was measured by quantitative real-time PCR. The sPG I and II levels and anti-H. pylori serum IgG were measured by ELISA. Results: The mtDNA-CN was found significantly higher in GC vs. non-GC (OR = 3.0; 95% CI = 1.4, 6.4) subjects. Conversely, GC patients had significantly lower sPG I/II ratio than the non-GC (OR = 3.2; CI = 1.4, 7.2) subjects. The combination of these two biomarkers yielded a dramatic amplification of the odds of GC risk in double-positive (high mtDNA-CN-low sPGI/II) subjects, in reference to double-negatives (low mtDNA-CN-high sPGI/II), when assessed against non-GC (OR = 27.1; CI = 5.0, 147.3), CG (OR = 13.1; CI = 2.4, 72.6), or NM (OR = 49.5; CI = 7.9, 311.6) groups. Conclusion: The combination of these two biomarkers, namely mtDNA-CN in PBLs and serum PG I/II ratio, drastically enhanced the efficiency of GC risk assessment, which calls for further validations.
Keywords
Biomarkers
DNA copy number variation
Mitochondrial DNA
Stomach neoplasmsr