Examination of lung cancer stem cell markers in tumor-derived exosomes obtained from bronchial lavage fluid and serum and their prognostic importance

ABSTRACT Examination of Lung Cancer Stem Cell Markers in Tumor-Derived Exosomes Obtained from Bronchial Lavage Fluid and Serum and Their Prognostic Importance Objective: Lung cancer is the most common cause of death in all cancer type. Due to the high mortality and morbidity of the disease and the high side effects of chemotherapy, targeted therapies have come to the fore. In this context, the detection of sensitive molecular markers will contribute greatly to the diagnosis, treatment, prognosis and follow-up of patients. Tumor-derived exosomes are small endosome vesicles that are increasingly used for cancer initiation, progression, monitoring of treatment and detection of resistance to treatment. In this study, it was aimed to examine cancer stem cell markers in tumor-derived exosomes obtained from bronchial lavage fluid and serum and to determine their prognostic importance. Material and Method: In order to isolate exosomes, bronchoalveolar lavage fluid or pleural fluid samples were taken from 104 patients with pre-diagnosis of lung cancer who applied to Çukurova University Medical Faculty Balcalı Hospital Chest Diseases Clinic. Demographic data, laboratory and pathological data and 6-month follow-up data of the patients were recorded. Proteins obtained from exosomes in 6 patients were separated into peptides by trypsin and the presence of cancer stem cell markers CD133 and ALDH1A1 was detected by mass spectroscopy analysis of peptides. Peaks-studio software program was used for analysis. Results: 104 patients were included in the study. Of the patients, 82 (78.8%) were male and 22 (21.2%) were female. The mean age of the patients was 64.3±10.5 (Med: 66, Min: 33, Max: 90) years. It was observed that 59 (56.7%) of the patients were smokers; It was determined that smokers consumed an average of 45.8±22.7 packs of cigarettes per year. In the protein analyzes performed on 6 patients, when the cancer patient group was compared with the control group, it was seen that most of the peptides were isolated from the cancer patient group and even from the lavage fluids of the small cell lung cancer (SCLC) patients. In the analysis results for cancer stem cell markers, a total of 3 peptides indicating the presence of CD133 were detected, while 1 peptide indicating ALDH1A1 was found. It was noteworthy that one of the CD133 detected samples belonged to a SCLC patient and one belonged to a patient with non- small cell lung cancer (NSCLC), while one of them was from the control sample group. The peptide sequences of ALDH1A1 were isolated only in the exosome obtained from the lavage fluid of NSCLC patient. Conclusion: In our study, which was conducted with a limited number of samples due to the pandemic and the rapid increase in the exchange rate, we demonstrated the presence of markers of cancer stem cells in exosomal proteins obtained from the lavage and serum of patients. It is thought that comprehensive studies to be conducted in larger groups will contribute to understanding the relationship of cancer stem cells detected in exosomes with the course of the disease and to revealing their prognostic importance. Key words: Lung cancer, Exosome, Cancer stemcell, CD133, ALDH1A1 IX