Abstract 2288: Cell-surface vimentin as a novel biomarker for detecting circulating tumor cells from advanced gastric cancer patients

Abstract

Abstract Background: Aberrant activation of epithelial-mesenchymal transition (EMT) is closely associated with gastric cancer (GC) progression and metastasis. However, biomarkers specifically capturing EMT-circulating tumor cells (EMT-CTCs) that can be used to noninvasively determine the disease status and prognosis in GC patients have been lacking. Patients and Methods: To fill this gap, we performed a head-to-head comparison clinical study between CSV+CTCs and EpCAM+CTCs using proprietary cell-surface vimentin (CSV) antibody 84-1 from MD Anderson and the epithelial tumor markers EpCAM and CK based on previous established CTCs detection method from 100 resectable and unresectable GC patients and 10 healthy donors. Also, freshly procured GC primary tissues and metastatic lymph nodes were obtained from five patients. Additionally, in vitro experiments were performed to investigate the role of CSV as a specific EMT marker in GC cell lines. Results: Using 84-1 antibody, we detected CSV more exclusively expressing on lymph node metastasis than primary tumor of GC. Subsequent experiments in vitro showed that the expression level of CSV was correlated with EMT phenotype and migration ability in GC cells. A dramatic increase in the levels of vimentin bound to the surface of GC cells after IGF-I stimulation using flow cytometry which indicated CSV as a specific marker in GC cell populations undergoing EMT. We further enumerated relative higher number of CSV+CTCs in unresectable advanced GC patients and EpCAM+CTCs in resectable population with early stage; none was detected from healthy donors. From our observations, we defined a cutoff of < five or ≥ five CTCs as optimal threshold with respect to therapeutic response using ROC curves. CSV+CTC counts were significant in differentiating disease stable and progression populations in comparison to the EpCAM+CTC. Notably, patients with unfavorable CTCs at baseline had a significantly shorter median PFS and OS in advanced GC populations. These results also indicated that a summation of CTCs detected from both methods increased the sensitivity and specificity of CTCs in monitoring therapeutic response and prognosis prediction compared to individual test. Conclusions: Our data demonstrate that CSV is a highly EMT-CTCs specific marker that may assist in assessing treatment efficacy and prognosis in advanced GC patients; however, an independent prospective study with a large population will be necessary to fully validate the efficiency of this method. Note: This abstract was not presented at the meeting. Citation Format: Heming Li, Yuting Liu, Zhi Wang, Shanshan Liang, Xiangyu Kong, Wenzhi Liu, Tong Zhao, Xuening Ji, Gang Wang, Fuguang Wang, Ruoyu Wang. Cell-surface vimentin as a novel biomarker for detecting circulating tumor cells from advanced gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2288.