Nonhematogenic circulating aneuploid cells confer inferior prognosis and therapeutic resistance in gliomas. Issue 10 (8th August 2022) - Li, Mingxiao
Abstract: Aneuploidy is the hallmark of malignancy. Our previous study successfully detected nonhematogenic circulating aneuploidy cells (CACs) in types of gliomas. The current prospective clinical study aims to further precisely subcategorize aneuploid CACs, including CD31 − circulating tumor cells (CTCs) and CD31 + circulating tumor endothelial cells, and thoroughly investigate the clinical utilities of these different subtypes of cells. Co‐detection and analysis of CTCs and circulating tumor‐derived endothelial cells (CTECs) expressing CD133, glial fibrillary acidic protein (GFAP), or epidermal growth factor receptor variant III (EGFR vIII) were performed by integrated subtraction enrichment and immunostaining fluorescence in situ hybridization (SE‐iFISH) in 111 preoperative primary diffuse glioma patients. Aneuploid CACs could be detected in most de novo glioma patients. Among detected CACs, 45.6% were CD31 − /CD45 − aneuploid CTCs and the remaining 54.4% were CD31 + /CD45 − aneuploid CTECs. Positive detection of CTECs significantly correlated with disruption of the blood–brain barrier. The median number of large CTCs (L CTCs, >5 μm, 2) in low‐grade glioma (WHO grade 2) was less than high‐grade glioma (WHO grades 3 and 4) (3, p = 0.044), but this difference was not observed in small CTCs (S CTCs, ≤5 μm), CTECs or CACs (CTCs + CTECs). The numbers of CTCs, CTECs, or CACs in patients with contrast‐enhancing (CE) lesions considerably exceeded that of non‐CE lesions ( p < 0.05). Receiver operating characteristic curves demonstrated that CD31 + CTECs, especially L CTECs, exhibited a close positive relationship with CE lesions. Survival analysis revealed that the high number of CD31 − CTCs could be an adverse factor for compromised progression‐free survival and overall survival. Longitudinal surveillance of CD31 − CTCs was suitable for evaluating the therapeutic response and for monitoring potential emerging treatment resistance. Abstract : For the first time, our study demonstrated that quantified CD31+CTECs correlated with contrast‐enhancing lesions and blood‐brain barrier disruption, whereas the specific subtype of pre‐operative CD31‐CTCs was resistant to chemoradiotherapy, and may function as an effective prognosticator in prognosticating inferior prognosis. Our study provided a novel and fresh perspective to comprehensively detect and characterize aneuploid circulating rare cells in glioma patients and revealed their relevant unique clinical significance.