scholarly journals Epithelial circulating tumor cells with a heterogeneous phenotype are associated with metastasis in NSCLC

Author(s):  
Yujuan Zhang ◽  
Yu Men ◽  
Jianyang Wang ◽  
Puyuan Xing ◽  
Jun Zhao ◽  
...  

Abstract Objectives To analyze the clinical relevance of heterogeneous phenotypes of peripheral circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC). Materials and Methods CTCs in 5 mL venous blood were enriched using the Canpatrol™ CTC technique in 82 NSCLC patients. And then, CTCs were subjected to RNA in situ hybridization with a combination of epithelial (EpCAM and CK8/18/19) and mesenchymal (vimentin and TWIST1) markers. Results According to the fluorescent dots, CTCs were classified into three groups, including epithelial CTCs (E-CTC), hybrid epithelial/mesenchymal phenotypes (E/M-CTCs) and mesenchymal CTCs (M-CTCs). In 82 NSCLC cohort, only 2 patients didn’t detect CTCs, the overall CTCs detection rate was 97.5% (80/82). For 60 treatment naïve NSCLC, only one patient didn’t detect CTCs. The median number of total CTCs, hybrid E/M phenotype CTCs, E-CTCs and M-CTCs per 5 mL blood was 22 (range 1–90), 13 (range 0–83), 1 (range 0–17 and 0–47), respectively. Hybrid E/M CTCs, especially the e = m-CTCs, significantly differed between patients with and without distant metastasis. M-CTCs in advanced NSCLC patients were significantly more than the numbers observed in early stage patients. Patients with pure hybrid E/M-CTCs showed a lower proportion in distant metastasis positive cohort compared to negative ones (7% vs 22%), while patients with E + E/M CTCs (20% vs 9%) and E/M + M CTCs (33% vs 20%) showed a higher proportion. CTCs dynamic changes after treatment in 12 advanced NSCLC patients suggested that hybrid E/M-CTCs were related to the primary tumor size at baseline, while M-CTCs may suggest the progression of NSCLC. Conclusion We concluded that E-CTCs with a hybrid E/M phenotype are associated to metastasis in therapy-naïve NSCLC patients.

Cancers ◽  
2014 ◽  
Vol 6 (1) ◽  
pp. 153-165 ◽  
Author(s):  
Laura Muinelo-Romay ◽  
Maria Vieito ◽  
Alicia Abalo ◽  
Marta Nocelo ◽  
Francisco Barón ◽  
...  

2016 ◽  
Vol 151 (3) ◽  
pp. 852-858 ◽  
Author(s):  
Rishindra M. Reddy ◽  
Vasudha Murlidhar ◽  
Lili Zhao ◽  
Svetlana Grabauskiene ◽  
Zhuo Zhang ◽  
...  

2020 ◽  
Author(s):  
Jun Liu ◽  
Yongping Liu ◽  
Cheng Gu ◽  
Lei Zhang ◽  
Xujing Lu

Abstract Background: This study aimed to investigate the association of circulating tumor cells (CTCs) change during chemoradiation with the treatment response and survival profiles in advanced non-small cell lung cancer (NSCLC) patients.Methods: 58 advanced NSCLC patients underwent concurrent chemoradiation were enrolled, then their peripheral blood samples were collected pre-chemoradiation and at 1 months post-chemoradiation to assess the CTCs using a CTC-Biopsy system. Moreover, CTCs were classified as CTCs positive and CTCs negative according to CTCs’ count, and CTCs’ change was calculated. Additionally, response of chemoradiation was evaluated at 1 months post-chemoradiation, then progression-free survival (PFS) and overall survival (OS) were assessed. Results: Pre-chemoradiation CTCs positive was associated with increased TNM stage, but not correlated with other clinicopathologic characteristics. After chemoradiation, the CTCs’ number (1.0 (0.0-3.0) vs. 4.0 (2.0-10.0)) and the percentage of CTCs positive cases (37.9% vs. 77.6%) were both decreased compared with those prior to chemoradiation. Regarding treatment response, pre-chemoradiation CTCs positive was associated with lower partial response; post-chemoradiation CTCs positive was associated with reduced disease control rate; while CTCs’ change during chemoradiation was not associated with treatment response. Kaplan–Meier curves showed that post-chemoradiation CTCs positive and increased CTCs’ number during chemoradiation were associated with reduced PFS, then multivariate Cox’s regression analysis disclosed that they independently predicted decreased PFS. However, no correlation of CTCs status or CTCs’ change with OS was observed. Conclusions: Longitudinal monitoring of CTCs may provide important reflection for the prognosis in chemoradiation treated advanced NSCLC patients.


Human Cell ◽  
2021 ◽  
Author(s):  
Yan Lu ◽  
Yushuang Zheng ◽  
Yuhong Wang ◽  
Dongmei Gu ◽  
Jun Zhang ◽  
...  

AbstractLung 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.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3294
Author(s):  
Wen-Sy Tsai ◽  
Tsung-Fu Hung ◽  
Jia-Yang Chen ◽  
Shu-Huan Huang ◽  
Ying-Chih Chang

Background: This study used NeuN transgenic (NTTg) mice with spontaneous breast tumor development to evaluate the dynamic changes of circulating tumor cells (CTCs) prior to and during tumor development. Methods: In this longitudinal, clinically uninterrupted study, we collected 75 μL of peripheral blood at the age of 8, 12, 16, and 20 weeks in the first group of five mice, and at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability in the second group of four mice. Diluted blood samples were run through a modified mouse-CMx chip to isolate the CTCs. Results: The CTC counts of the first group of mice were low (1 ± 1.6) initially. The average CTC counts were 16 ± 9.5, 29.0 ± 18.2, and 70.0 ± 30.3 cells per 75 μL blood at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability, respectively. There was a significant positive correlation between an increase in CTC levels and tumor vascular density (p-value < 0.01). This correlation was stronger than that between CTC levels and tumor size (p-value = 0.076). The captured CTCs were implanted into a non-tumor-bearing NTTg mouse for xenografting, confirming their viability and tumorigenesis. Conclusion: Serial CTCs during an early stage of tumor progression were quantified and found to be positively correlated with the later tumor vascular density and size. Furthermore, the successful generation of CTC-derived xenografts indicates the tumorigenicity of this early onset CTC population.


Sign in / Sign up

Export Citation Format

Share Document