Abstract

Abstract Background: Early diagnosis is associated with a better prognosis, and improved survival rates for lung cancer patients. Exosomes of liquid biopsy is rapidly introduced in clinical practice, providing possibilities to offer accurate information. We previously reported that tumor draining pulmonary vein blood (TDVP) derived exosomes were increased than the periphery, and GRIP and coiled-coil domain containing 2 (GCC2) in exosomes act as potential lung adenocarcinoma biomarkers. The purpose of this study to evaluate the diagnostic value of exosome enriched GCC2 in peripheral blood and TDPV in patients with lung cancer who underwent surgery. Methods: The utilization of exosome GCC2 in the TDPV of lung cancer for clinically informative diagnosis was investigated using rabbit lung cancer model, healthy control rabbits, patients with surgically resected lung adenocarcinoma, and healthy controls. Exosome GCC2 levels were measured using an enzyme-linked immunosorbent assay (ELISA) and receiver operating characteristic curves were used to calculate the diagnostic efficiency of carcinoembryonic antigen (CEA), exosome CD63, plasma GCC2, and exosome GCC2. Results: In the rabbit lung cancer model, the expression of exosome GCC2 from the TDPV significantly increased compared with that in the periphery, as determined by western blotting. Of the 70 patients included in the study, and the mean age of all patients was 65.8 ± 9.0 years. The AUC values of CEA according to the blood sampling sites were not significant (all p > 0.05). By contrast, the AUC values of CD63 were 80.0% for TDPV (p < 0.0001) and 55.0% for the periphery (p = 0.42), respectively. The AUC values of plasma GCC2 in the periphery and TDPV were 68.0% (p > 0.05) and 74.0% (p < 0.0001), respectively. Importantly, the diagnostic accuracy values of exosome GCC2 in the periphery and TDPV were 81.0% (p < 0.0001) and 90.0% (p < 0.0001), respectively. The increasing trend of exosome GCC2 in the TDPV had a significantly higher correlation with pathological stages than that of the periphery (periphery, p < 0.05; TDPV, p < 0.0001). Moreover, exosome GCC2 in the TDPV was associated with pathological stage (p < 0.001), lymph node metastasis (p < 0.01), and lymphatic invasion (p < 0.05). Conclusion: Exosome enriched GCC2 in the TDPV was significantly correlated with pathological stages and accurate AUL value than that in the periphery. Exosome GCC2 in TDPV may be a promising and clinically informative biomarker for patients with lung cancer who have undergone surgery. Citation Format: Byeong Hyeon Choi, Yu Hua Quan, Jiyun Rho, Kyungsu Kim, Jun Hee Lee, Yeonho Choi, Yong Park, Ji-Ho Park, Sunghoi Hong, Hyun Koo Kim. Exosome enriched GCC2 in tumor draining pulmonary blood plasma as a clinically informative biomarker in patients with surgically resected lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB517.

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