Gene expression profiling and DNA methylation analyses of CTCs

Lianidou, Evi

doi:10.1016/j.molonc.2016.01.011

Cited by 50 publications

(31 citation statements)

References 105 publications

(143 reference statements)

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“…Other salient forms of information can be gleaned from individual CTCs, including epigenetics, proteomics and metabolomics. Single-CTC methylation analysis was recently demonstrated by Huang and colleagues, indicating at a gross level that DNA was hypomethylated and RNA was hypermethylated [162,163]. Along similar lines, methylation patterns in ctDNA has been used to identify tissue-specific cell death [164], and ctDNA detection of aberrant promoter methylation in a six-gene panel has been used for diagnosing breast cancer [165].…”

Section: Conclusion and Future Perspectivementioning

confidence: 89%

The Promise of Circulating Tumor Cells for Precision Cancer Therapy

Hwang

Miyamoto

2016

Biomark. Med.

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The rapidly growing array of therapeutic options in cancer requires informative biomarkers to guide the rational selection and precision application of appropriate therapies. Circulating biomarkers such as circulating tumor cells have immense potential as noninvasive, serial 'liquid biopsies' that may be more representative of the complete spectrum of a patient's individual malignancy than spatially and temporally restricted tumor biopsies. In this review, we discuss the current state-of-the-art in the isolation and molecular characterization of circulating tumor cells as well as their utility in a wide range of clinical applications such as prognostics, treatment monitoring and identification of novel therapeutic targets and resistance mechanisms to enable real-time adjustments in the clinical management of cancer. The evolving landscape of cancer therapy creates an urgent need for minimally invasive biomarkers to facilitate early detection, prognosis and prediction of therapeutic response and resistance to enable highly adaptable, real-time precision therapy [1]. The conventional gold standard of using single biopsies of the primary tumor to inform all downstream therapeutic decisions may no longer be adequate given increasing evidence of significant spatial and temporal hetero geneity in tumors [2], especially when placed under the selection pressure of various treatments. Moreover, serial biopsies are often impractical, morbid and technically challenging.In this review, we focus on the emerging role of circulating tumor cells (CTCs), which can be serially obtained from minimally invasive blood draws or 'liquid biopsies'. CTCs are cancer cells that have been shed into the peripheral circulation from primary or metastatic tumors [3,4]. The first reported observation of CTCs was in 1869 by Australian pathologist Thomas Ashworth at the autopsy of a patient with metastatic cancer [5]. By comparing the morphology of circulating cells with those from different cancerous lesions, Ashworth came to the prescient conclusion that 'cells identical with those of the cancer itself being seen in the blood may tend to throw some light upon the mode of origin of multiple tumors existing in the same person' [5]. Indeed, molecular analyses of CTCs may be superior to individual tumor biopsies because these circulating cells likely provide a sampling of different regions of the primary tumor as well as metastatic deposits, and therefore are more likely to capture the genetic heterogeneity of a patient's cancer.While cell-free circulating tumor DNA (ctDNA) is an important, complementary biomarker to CTCs, it has been reviewed extensively elsewhere and will not be discussed in this review [4,6]. Moreover, although ctDNA may in some cases be more reliably [7], they are largely limited to genomic mutational analysis. In contrast, CTC analysis can provide a wealth of other information including cell morphology, immunocytochemical phenotype, presence of important epitopes, presence of multiple mutations within a single cell to decode ...

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Section: Conclusion and Future Perspectivementioning

confidence: 89%

The Promise of Circulating Tumor Cells for Precision Cancer Therapy

Hwang

Miyamoto

2016

Biomark. Med.

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“…Molecular assays take advantage of the extreme sensitivity and specificity of polymerase chain reaction (PCR), can be in silico designed, and are high throughput and subjected to internal and external quality control systems. After isolation of total RNA from viable CTCs, and subsequent real‐time (RT)‐PCR amplification, important information on the expression of a variety of tumor or epithelial‐specific targets can be derived . Many groups have verified the importance of using molecular assays for CTC molecular characterization.…”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

“…After isolation of total RNA from viable CTCs, and subsequent real-time (RT)-PCR amplification, important information on the expression of a variety of tumor or epithelialspecific targets can be derived. 29,30 Many groups have verified the importance of using molecular assays for CTC molecular characterization. Molecular assays based on RT-PCR performed in nucleic acids material (RNA or genomic DNA) isolated from the EpCAM-positive CTC fraction can give valuable information for the molecular characterization of CTC at the gene expression level, 22,31-36 and even at the single-cell level.…”

Section: Analytical Systems For Ctc Isolation Enumeration and Detmentioning

confidence: 99%

Liquid biopsies

Lianidou

Pantel

2019

Genes Chromosomes & Cancer

131

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Liquid biopsy is based on minimally invasive blood tests and has a high potential to significantly change the therapeutic strategy in cancer patients, providing an extremely powerful and reliable noninvasive clinical tool for the individual molecular profiling of patients in real time. Liquid biopsy approaches include the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating miRNAs, and tumor‐derived extracellular vesicles (EVs) that are shed from primary tumors and their metastatic sites into peripheral blood. The major advantage of liquid biopsy analysis is that it is minimally invasive, and can be serially repeated, thus allowing extracting information from the tumor in real time. Moreover, the identification of predictive biomarkers in peripheral blood that can monitor response to therapy in real time holds a very strong potential for novel approaches in the therapeutic management of cancer patients. In this review, we summarize recent knowledge on CTCs and ctDNA and discuss future trends in the field.

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“…TTF-1 is considered as highly specific marker for lung adenocarcinomas (56). The utilization of gene expression profiling is well-established in breast cancer; expression levels of ER, PR and HER2 in the primary tumor, but also possibly in CTCs, are used to choose appropriate hormone treatment (57).…”

Section: Morphology and Biological Features Morphological Evaluationmentioning

confidence: 99%

Circulating Tumor Cells in Diagnosis and Treatment of Lung Cancer

Malý

Kološtová

et al. 2019

In Vivo

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Circulating tumor cells (CTCs), detached from the primary tumor or metastases and shed in the patient's bloodstream, represent a relatively easily obtainable sample of the cancer tissue that can indicate the actual state of cancer, and their evaluation can be repeated many times during the course of treatment. As part of liquid biopsy, evaluation of CTCs provides a lot of clinically relevant information, which reflects the actual, real-time conditions of the disease. CTCs can be used in cancer diagnosis or screening, real-time longterm disease monitoring and even therapy guidance. Their analysis can include their number, morphology, and biological features by using immunocytochemistry and all "-omic" technologies. This review describes methods of CTC isolation and potential clinical utilization in lung cancer. Despite major advances in the diagnostics and treatment, lung cancer remains the most lethal cancer disease on a global scale. According to a WHO estimate, there were 2.09 million new lung cancer cases and 1.76 million lung cancer-related deaths in 2018 (1). Therefore, similarly to other cancer diagnoses, a significant effort is dedicated on the potential use of circulating tumor cells (CTCs) in prognosis assessment, disease monitoring and even in therapy management. CTCs, detached from the primary tumor or metastases and shed in patient's bloodstream, represent a relatively easily obtainable sample of cancer tissue. As a liquid biopsy, evaluation of CTCs provides a lot of clinically relevant information, which reflects the actual, real-time conditions of the disease (2). CTCs are very rare in the bloodstream; therefore, a number of different enrichment and isolation methods have been developed (2). Also, the evaluation of CTCs can be performed on many levels providing different kinds of information. The CTCs enrichment methods as well as their potential clinical use in lung cancer is introduced below. CTC Isolation and Detection Methods-Basic Principles Exploration of CTCs can provide a lot of clinically-relevant information; however, CTCs are very rare in the bloodstream. Every single CTC is surrounded by 10 6-10 7 mononuclear white blood cells (2, 3). Therefore, in order to be able to study and assess CTC-number and characteristics, it is necessary to separate them from the ambient blood cells. Although many methods have been developed to isolate CTCs, there are only two basic approaches to isolate CTCs: a) isolation methods based on detection of specific surface markers of the CTCs (and/or white blood cells), also called "label-dependent systems/methods" and b) methods independent of specific markers, based on physical or biological properties of the CTCs, "label-independent systems/methods" (2).

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Gene expression profiling and DNA methylation analyses of CTCs

Cited by 50 publications

References 105 publications

The Promise of Circulating Tumor Cells for Precision Cancer Therapy

The Promise of Circulating Tumor Cells for Precision Cancer Therapy

Liquid biopsies

Circulating Tumor Cells in Diagnosis and Treatment of Lung Cancer

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