Detection of GALNT13 in circulating tumor cells of non-small cell lung cancer (NSCLC) patients. A potential new liquid biopsy biomarker.

Abstract

Introduction. Protein O-glycosylation abnormalities are found in most carcinomas. Several clinically useful biomarkers detecting these changes have been developed. The synthesis of mucin-type O-glycans starts in a reaction catalyzed by a complex enzyme family (UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases; GalNAc-Ts), which has at least 20 members in humans. We previously found that GalNAc-T13 isoenzyme is a strong predictor of poor clinical outcome in neuroblastoma1 and breast cancer patients2. Given that GalNAc-T13 is also expressed in NSCLC3, this work aimed to evaluate GALNT13 expression in circulating tumor cells (CTC) as a new potential liquid biopsy biomarker in NSCLC patients. Methods. GALNT13 expression in CTC was evaluated by a nested RT-PCR method in 119 NSCLC patients from Hospital Maciel, Montevideo. Results were correlated with clinical-pathologic data and patients’ survival. Results. No expression of GALNT13 was found in 20 healthy individuals’ samples and the sensitivity of the method was established at 0.01%. GALNT13-positive CTCs were found in 72/119 (60.5%) lung cancer patients. Concerning histological types, GALNT13 expression was detected in adenocarcinoma patients (36/62; 58.1%), as well as squamous cell carcinomas patients (20/33; 60.6%). Relating to stages, the enzyme was found in 13/19 (68.4%) of patients with stages I/II, 16/33 (48.5%) of stages IIIA/IIIB, and 43/69 (62.3%) of stages IIIC/IV. In this preliminary evaluation, we attained three years of follow-up. In early-stage patients (I/II) 6/13 (46.1%) of GALNT13-positive died, in contrast to none of the negative ones (0/6). In intermediate stages (IIIA/IIIB) 10/16 (62.5%) of GALNT13-positive and 8/17 (47.1%) of negative patients died. Finally, in advanced stages (IIIC/IV) death occurred in 31/43 (72.1%) of GALNT13-positives and 20/24 (83.3) of negative patients. Conclusion. In this study, we suggest that GALNT13 expression in CTC could be a potential new biomarker in liquid biopsy for lung cancer patients.