Correlation of Short Leukocyte Telomeres and Oxidative Stress with the Presence and Severity of Lung Cancer Explored by Principal Component Analysis

Belić, Milica; Sopić, Miron; Roksandić-Milenković, Marina; Ćeriman, Vesna; Guzonijić, Azra; Vukašinović, Aleksandra; Ostanek, Barbara; Dimić, Nemanja; Jovanović, Dragana; Kotur-Stevuljević, Jelena

doi:10.14712/fb2023069020059

Folia Biologica > Archive > 2023, Vol. 69 > Issue 2 > Correlation of Short Leukocyte Telomeres…

Fol. Biol. 2023, 69, 59-68

https://doi.org/10.14712/fb2023069020059

Correlation of Short Leukocyte Telomeres and Oxidative Stress with the Presence and Severity of Lung Cancer Explored by Principal Component Analysis

Milica Belić¹, Miron Sopić², Marina Roksandić-Milenković³, Vesna Ćeriman⁴, Azra Guzonijić², Aleksandra Vukašinović⁵, Barbara Ostanek⁶, Nemanja Dimić⁷, Dragana Jovanović⁸, Jelena Kotur-Stevuljević²

¹PrimeVigilance d.o.o., Belgrade, Serbia
²Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Serbia
³Municipality Institute for Lung Diseases and Tuberculosis, Belgrade, Serbia
⁴Institute for Lung Diseases, Thoracic Surgery and Tuberculosis, Clinical Center of Serbia, Belgrade, Serbia
⁵Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy
⁶Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Slovenia
⁷University Clinical-Hospital Center Dr. Dragisa Misovic, Belgrade, Serbia
⁸Internal Medicine Clinic “Akta Medica”, Belgrade, Serbia

Received June 2023
Accepted October 2023

Lung cancer (LC) is the second most common malignancy and leading cause of cancer death. The potential “culprit” for local and systemic telomere shortening in LC patients is oxidative stress. We investigated the correlation between the peripheral blood leukocyte (PBL) telomere length (TL) and the presence/severity of LC and oxidative stress, and its usefulness as LC diagnostic marker. PBL TL was measured in 89 LC patients and 83 healthy subjects using the modified Cawthon RTq-PCR method. The relative PBL TL, found to be a potential diagnostic marker for LC with very good accuracy (P < 0.001), was significantly shorter in patients compared to the control group (CG) (P < 0.001). Significantly shorter telomeres were found in patients with LC TNM stage IV than in patients with stages I-III (P = 0.014), in patients without therapy compared to those on therapy (P = 0.008), and in patients with partial response and stable/progressive disease compared to those with complete response (P = 0.039). The total oxidant status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB) and C-reactive protein (CRP) were significantly higher in patients compared to CG (P < 0.001) and correlated negatively with TL in both patients and CG (P < 0.001). PCA showed a relation between PAB and TL, and between the EGFR status and TL. Oxidative stress and PBL telomere shortening are probably associated with LC development and progression.

Keywords

lung cancer, peripheral blood telomere length, oxidative stress.

Funding

This study was supported by the Ministry of Education, Science and Technological Development, Republic of Serbia through Grant Agreement with the University of Belgrade – Faculty of Pharmacy No.: 451-03-9/2021-14/200161 and CEEPUS project Novel Diagnostic and Therapeutic Approaches to Complex Genetic Disorders CIII-SI-0611-08-1819.