Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy

Zhong, Xiaoming; Zhang, Hangtian; Zhu, Ying; Liang, Yuqing; Yuan, Zhuolin; Li, Jiachen; Li, Jing; Li, Xin; Jia, Yixin; Tian, He; Zhu, Jinxin; Sun, Yu; Jiang, Wengting; Zhang, Hui; Wang, Cheng; Ke, Zunfu

doi:10.1186/s12943-020-1141-9

Cited by 98 publications

(77 citation statements)

References 90 publications

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“…Over the past decades, CTCs have been considered as a potential candidate for the “liquid biopsy” since they act as “snapshot” of the primary tumour [ 16 , 17 ]. Recent studies showed that heterogeneous CTCs were often detected from the blood and were phenotypically and genetically different from the primary tumour [ 18 , 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Heterogeneity of Single Circulating Tumour Cells in Colorectal Carcinoma

Hamid

Gopalan

Matos

et al. 2020

IJMS

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The aim of the present study was to isolate and investigate the genetic heterogeneities in single circulating tumour cells (CTCs) from patients with colorectal carcinoma (CRC). Twenty-eight single CTCs were collected from eight patients with CRC using a negative immunomagnetic enrichment method. After validation with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expression in 3 colon cancer cell lines, a panel of 19 genes were used to analyse the single CTCs (n = 28), primary colorectal carcinoma tissues (n = 8) and colon carcinoma cells (n = 6) using real-time qPCR. Genetic heterogeneities were assessed by comparing gene expression profiles of single CTCs from the different patients and in the same patient, respectively. Genetic profiling of the single CTCs showed extensive heterogeneities of the selected genes among the CTCs. Hierarchical clustering analyses exhibited two clusters of CTCs with differentially expressed genes, which highlighted different modifications from the primary carcinomas. Further, the genetic heterogeneities were observed between different patients or in the same patient. Finally, AKT1 expression was significantly (p = 0.0129) higher in single CTCs from CRC of advanced pathological stages (III or IV) CRC than in CTCs from CRC of early stages (I or II). Our findings suggest that single-cell genetic analysis can monitor the genetic heterogeneities and guide the personalised therapeutic targets in clinical sectors.

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Section: Discussionmentioning

confidence: 99%

Genetic Heterogeneity of Single Circulating Tumour Cells in Colorectal Carcinoma

Hamid

Gopalan

Matos

et al. 2020

IJMS

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“…CTCs are considered to be responsible for the distant metastasis of tumors [ 21 ]. As a liquid biopsy, CTC enumeration could predict disease progression and treatment response, while molecular analysis may provide deep insights into mechanisms of tumor metastasis and guide the development of therapeutic strategies [ 22 , 23 , 24 ]. In recent years, advancements in microfluidic techniques have provided us lots of new tools for cellular biology studies.…”

Section: Discussionmentioning

confidence: 99%

Design and Clinical Application of an Integrated Microfluidic Device for Circulating Tumor Cells Isolation and Single-Cell Analysis

Liu

Zou

et al. 2021

Micromachines

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Circulating tumor cells (CTCs) have been considered as an alternative to tissue biopsy for providing both germline-specific and tumor-derived genetic variations. Single-cell analysis of CTCs enables in-depth investigation of tumor heterogeneity and individualized clinical assessment. However, common CTC enrichment techniques generally have limitations of low throughput and cell damage. Herein, based on micropore-arrayed filtration membrane and microfluidic chip, we established an integrated CTC isolation platform with high-throughput, high-efficiency, and less cell damage. We observed a capture rate of around 85% and a purity of 60.4% by spiking tumor cells (PC-9) into healthy blood samples. Detection of CTCs from lung cancer patients demonstrated a positive detectable rate of 87.5%. Additionally, single CTCs, ctDNA and liver biopsy tissue of a representative advanced lung cancer patient were collected and sequenced, which revealed comprehensive genetic information of CTCs while reflected the differences in genetic profiles between different biological samples. This work provides a promising tool for CTCs isolation and further analysis at single-cell resolution with potential clinical value.

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“…But it is difficult to develop CTCs as a diagnostic marker, because the number of CTCs was extremely low in the peripheral blood. Different detection methods obtained different CTC numbers in different volumes of blood [31]. Recently, Teixeira et al enriched and sequencing the CTCs collected from 7.5 mL peripheral blood of patients with pre-invasive squamous cell lung cancer lesions using Cellsearch system [32].…”

Section: Discussionmentioning

confidence: 99%

“…However, developing CTCs as a diagnostic marker is challenging because of the scarce number of CTCs in the peripheral blood. Studies using different detection methods have reported different CTC numbers in different blood volumes [32] . For example, Teixeira et al.…”

Section: Discussionmentioning

confidence: 99%

The value of circulating tumor cells with positive centromere probe 8 in the diagnosis of small pulmonary nodules

Liu

Chen

Wang³

et al. 2021

Translational Oncology

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Background Circulating cancer cells (CTCs) provide opportunities for early diagnosis and evaluation of cancer stage as a more acceptable non-invasive liquid biopsy. The advanced development and use of CTCs for diagnosis or prognosis just started in recent years. Methods Fifty three patients, diagnosed as SPNs with a diameter less than 30 mm by CT examination, was enrolled for statistical analysis based on their CTCs level, CT examination features, serum tumor marker concentrations, and histopathological characteristics. Centromere probe 8 (CEP8) was utilized as a marker for CTCs determination. Results The CTCs level was significantly different between malignant and benign SPNs, as well as between early (0/Ia) and advanced (Ib/II/III) stages of lung cancer. For the malignancy judgment and the pTNM stage diagnosis of SPNs, ROC analysis results showed that combined use of CTCs level or density feature of CT morphology significant improved diagnostic effect compared to use of these two markers solely. Moreover, in bigger, single, and solid SPNs based on CT morphology, the CTCs level significantly correlated with the malignant histopathology. Additionally, triple staining (CEP8, EpCAM and CKs) results using samples from 22 out of 53 patients showed that more CTCs was detected when CEP8 was used as a marker. Conclusion The CTCs determined by CEP8 positive would be a potential adjuvant diagnostic marker for the malignance and stage of lung cancer for patients with SPNs.

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Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy

Cited by 98 publications

References 90 publications

Genetic Heterogeneity of Single Circulating Tumour Cells in Colorectal Carcinoma

Genetic Heterogeneity of Single Circulating Tumour Cells in Colorectal Carcinoma

Design and Clinical Application of an Integrated Microfluidic Device for Circulating Tumor Cells Isolation and Single-Cell Analysis

The value of circulating tumor cells with positive centromere probe 8 in the diagnosis of small pulmonary nodules

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