Prognostic value of the DNA integrity index in patients with malignant lung tumors

Abstract

// Dimple Y. Chudasama 1, 2 , Zeynep Aladag 2 , Mayla I. Felicien 2 , Marcia Hall 2 , Julie Beeson 1 , Nizar Asadi 1 , Yori Gidron 3 , Emmanouil Karteris 2 and Vladimir B. Anikin 1 1 Division of Thoracic Surgery, The Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, London, UK 2 Division of Biosciences, Brunel University London, London, UK 3 Scalab, Lille University, Oncolille, Lille, France Correspondence to: Vladimir B. Anikin, email: V.Anikin@rbht.nhs.uk Keywords: circulating tumour DNA; Alu repeats; DNA integrity index; malignant lung tumours; liquid biopsy Received: August 12, 2017     Accepted: March 06, 2018     Published: April 20, 2018 ABSTRACT Introduction: Lung cancer survival remains poor in the western world due to late presentation in most cases, leading to difficulty of treatment in these advanced and metastatic patients. Therefore, the development of a robust biomarker for prognosis and to monitor treatment response and relapse would be of great benefit. The use of Alu repeats and DNA Integrity Index has been shown to hold both diagnostic and prognostic value, and as it is obtained from the plasma of patients, it can serve as a non-invasive tool for routine monitoring. This study evaluates the efficiency of this technique in malignant lung cancer patients. Methods: Plasma samples were collected from 48 patients, consisting of 29 lung cancer patients and 19 non-cancer controls. Alu repeat ratio and confounders were measured. Results: Observations showed a higher Alu repeat ratio amongst the cancer group compared to controls ( p=0.035) , mean Alu ratio 0.38 (range 0.01-0.93) and 0.22 (0.007-0.44) respectively, ROC curve analysis AUC 0.61 (p=0.22) . Analysis by staging was more promising, whereby a higher DNA Integrity Index was seen in advanced cases compared to both early stage and controls, p<0.0001; AUC: 0.92 (P=0.0002) and p=0.0006, AUC – 0.88 (p=0.0007) respectively, however no significant difference was observed in the early stage compared to controls. Short term survival data also showed a DNA Integrity Index of >0.5 to be associated with poorer overall survival p=0.03 . Conclusion: The results of this study show a potential use of Alu repeats ratios for prognostic purposes in the advanced setting for lung cancer patients.