Dataset Information

FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis.

ABSTRACT: Lung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.

SUBMITTER: Lu Y

PROVIDER: S-EPMC8057988 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis.

Lu Yan Y Zheng Yushuang Y Wang Yuhong Y Gu Dongmei D Zhang Jun J Liu Fang F Chen Kai K Guo Lingchuan L

Human cell 20210212 3

Lung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify ...[more]

PMID: 33580470

Similar Datasets

Project description:Using nonenrichment-based, potentially more sensitive Epic Sciences circulating tumor cell (CTC) platform, we sought to detect and characterize CTCs in untreated, high-risk localized prostate cancer and to evaluate their clinical implication. Between 2012 and 2015, blood samples were prospectively collected from patients with National Comprehensive Cancer Network high-risk localized prostate cancer undergoing either radiotherapy (XRT) plus androgen deprivation therapy or radical prostatectomy (RP) with curative intent. Samples were analyzed with the Epic Sciences platform with 4J,6-diamidino-2-phenylindole, CD45, cytokeratin (CK), and androgen receptor (AR) N-terminal staining. CTC counts were correlated with biochemical recurrence (BCR). A diversity of CTC subtypes, including CK-positive, CK-negative, AR-positive, and CTC clusters, were observed in 73.3% (33 of 45) of patients with evaluable data. The median follow-up was 14.2 months (range, 0.5 to 43.7 months). BCR occurred more frequently in the RP group than XRT (15 of 26 v one of 19), with most patients in the XRT group continuing to receive androgen deprivation therapy. A higher proportion of metastatic events were observed in the RP group (five of 26 v one of 19). In the RP group, BCR and development of metastases were associated with a higher total number of CTCs, AR-positive CTCs, and CTC phenotypic heterogeneity. One patient who developed BCR and metastases quickly after RP had diverse phenotypical CTC subtypes, and single-cell genomic analyses of all detectable CTCs confirmed common prostate cancer copy number alterations and PTEN loss. CTCs can be identified in most patients with high-risk localized prostate cancer before definitive therapy using the Epic Sciences platform. If confirmed in a larger cohort with longer follow-up, phenotypic and genomic characterization of CTCs pretherapy may provide an additional means of risk stratifying patients with newly diagnosed high-risk disease and potentially help identify patients who could require multimodal therapy.

Project description:BackgroundVarious methods of liquid biopsy through the sampling of blood in cancer patients allow access to minuscule amounts of tumor that can easily be sampled repeatedly throughout therapy. Circulating tumor cells (CTCs) represent shed tumor cells that can be characterized by imaging or molecular techniques using an amenable enrichment platform. Here we validate the Hitachi Chemical Micro Cavity Array (MCA) for the enrichment of CTCs from the blood of patients diagnosed with stage III non-small cell lung cancer (NSCLC). MCA is a semi-automated filtration system that enriches CTCs on the basis of size and membrane deformability rather than a biased selection of surface antigens.MethodsCTCs were enriched from the peripheral blood of 38 patients diagnosed with stage III NSCLC at the start of chemoradiation. Two tubes of EDTA blood were collected from each patient and processed through MCA in parallel. In the first tube, CTCs were identified as pan-cytokeratin (CK)+ CD45- nucleated cells and enumerated. The second tube was depleted of leukocytes using CD45 antibody-coated magnetic microbeads before enrichment by MCA, followed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) to interrogate CTC-enriched lysates for expression of 16 target mRNAs from a panel of epithelial, mesenchymal, stem-like, and cancer signaling-related genes. CTC-enriched lysates from similarly prepared peripheral blood samples from 18 healthy donors were used to define positive gene expression.ResultsCTCs were identified by imaging in 30 of 38 patient samples (79%). At least 1 target gene was positively expressed in 23 of 25 (92%) patient samples that was subjected to molecular characterization. A CTC count of ≥7 was associated with poor progression-free survival (PFS) [hazard ratio (HR) 4.24, 95% confidence interval (CI), 1.73-10.40, P=0.020] and poor overall survival (HR 8.17, 95% CI, 2.87-23.26, P<0.001). Expression of BCL2 by MCA-enriched CTCs was associated with poor PFS (HR 3.11, 95% CI, 1.18-8.22, P=0.022). Individually, CTC count and expression of BCL2 each remained statistically significant predictors of disease progression and overall survival in multivariate analysis.ConclusionsThis is the first demonstration that lysates of MCA-enriched CTCs are amenable to molecular characterization. CTCs enriched by MCA are an independent prognostic marker in NSCLC.

Project description:BackgroundIt has been considered that the detection methods for circulating tumor cells (CTCs) based on epithelial cell adhesion molecule (EpCAM) underestimate the number of CTCs and may miss a metastatic subpopulation with cancer stem cell (CSC) properties. Therefore, we investigated EpCAM-positive and -negative CTCs in non-small cell lung cancer (NSCLC) patients at different stages, assessed the clinical value of these CTCs and explored their capacity in the following CSC model.MethodsCTCs were enriched by the depletion of leukocytes with bi-antibodies using a magnetic bead separation technique and then identified by the expression of EpCAM and cytokeratin 7 and 8 using multi-parameter flow cytometry. We determined the distribution of CTCs classified by the expression of EpCAM in 46 NSCLC patients with stages I to IV, assessed the diagnostic value of these CTCs by longitudinal monitoring in 4 index patients during adjuvant therapy and characterized the stemness of these CTCs by the expression of CXCR4 and CD133 in 10 patients.ResultsEpCAM-negative (E-) CTCs were detected to be significantly higher than EpCAM-positive (E+) CTCs in stage IV (p = 0.003). The patients with the percentage of E-CTCs more than 95% (r > 95%) were detected to be significantly increased from 13.3% in stage I-II to 61.1% in stage IV (p = 0.006). Kaplan-Meier analysis indicated that the patients with r > 95% had significantly shorter survival time than those with r ≤ 0.95 (p = 0.041). Longitudinal monitoring of CTCs indicated that the patients with a high percentage of E-CTCs in the blood were not responsive to either chemotherapy or targeted therapy. Further characterization of CTCs revealed that a stem-like subpopulation of CXCR4+CD133+ CTCs were detected to be significantly more prevalent in E-CTCs than that in E+CTCs (p = 0.005).ConclusionsThe enrichment of CTCs by the depletion of leukocytes with bi-antibodies is a valuable method for estimating the number of CTCs, which can be potentially applied in predicting the prognosis, monitoring the therapeutic effect of NSCLC patients and further analyzing the biology of CTCs.

Dataset Information

FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis.

Publications

FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets