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BACKGROUND: PD-L1 in pathological tissue samples is known as a biomarker for immune checkpoint inhibitors (ICI) to unresectable non-small cell lung cancer (NSCLC) patients. However, collecting pathological tissue is highly invasive, and lower invasive test is needed. As an alternative diagnostic target, circulating cancer cells (CTCs) that are known to exist in the peripheral blood of cancer patients are garnering attention. PURPOSE: The goal of this study is to verify the utility of CTC analysis isolated by a novel system (Sysmex, Hyogo) against pathological testing of tumor samples. The primary objective is to determine whether CTCs can be detected in unresectable NSCLC patients, and the secondary objective is to evaluate the relationship between CTCs and clinicopathological features or clinical outcome. METHODS: Blood samples were collected from 45 patients with unresectable NSCLC and 17 healthy controls. CTCs were size-dependently enriched from whole blood, immunofluorescent stained with pan-CK (AE1/AE3), PD-L1, CD45/34/16, and Hoechst, and analyzed by Molecular Imaging Flow Cytometry (MI-1000). Fluorescence intensity and cell images of each marker were obtained by MI-1000. RESULTS: Cells positive for Hoechst but negative for blood cell markers were defined as non-blood cells (NBCs). Pan-CK positive NBCs were defined as CTCs. A similar number of NBCs were detected in both patients and healthy controls. When using a threshold set at two standard deviations above the mean fluorescence intensity of pan-CK and PD-LI of NBCs in healthy controls, 28.9% of patients had two or more CTCs. On the other hands, PD-L1 positive NBCs were only detected in patients, and the sensitivity of detecting CTCs or PD-L1 positive NBCs was 86.7%. Concordance with PD-L1 expression of tumor tissue was evaluated for three parameters: the number of PD-L1 positive NBCs, the median and the mean fluorescence intensities. The AUC in each case was low, indicating no concordance between PD-L1 expression of tumor tissue and CTCs. Additionally, no relation was found with the overall survivals and progression-free survival when comparing patients divided into two groups: those with two or more PD-L1 positive cells and those with less than two. CONCLUSION: The detected rate of pan-CK positive cells was low ( Citation Format: Mami Onishi, Eri Morita, Tetsuya Sakai, Yoshitaka Zenke, Masatoshi Yanagida, Koichi Goto. Development of a CTC-based novel diagnostic technology for unresectable non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3321. |
