Circulating Tumor Cells Versus Circulating Tumor DNA in Colorectal Cancer: Pros and Cons

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials. This review covers CTC- and ctDNA-related technologies and their application in colorectal cancer. The promise of CTC- and ctDNA-based liquid biopsies is envisioned.     

Parallel Evaluation of Circulating Tumor DNA and Circulating Tumor Cells in Metastatic Colorectal Cancer

Background

Tissue biopsy is the gold standard for tumor genotyping, but it is an invasive procedure providing a single snapshot into tumor heterogeneity. Liquid biopsy approaches, encompassing the analysis of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs), have been proposed as an alternative, with the potential of providing a comprehensive portrait of the tumor molecular landscape. In metastatic colorectal cancer (mCRC), both CTCs and ctDNA analysis have been investigated, but comparative analyses are limited.

The Clinical Potential of Circulating Tumor Cells and Circulating Tumor-Associated Cellular Elements in Colorectal Cancer

Colorectal cancer (CRC) remains one of the commonest types of cancer in the USA. Effective treatment and potential curative resection is dependent on early detection, prior to the development of distant metastases. Radiologic and endoscopic evaluations are operator-dependent and limited by macroscopic detection when the relative cellular tumor burden is already high. Also, use of serum biomarkers such as carcinoembryonic antigen may not correlate with the extent of disease involvement. Circulating tumor cells (CTCs) continue be a prominent area of investigation, despite having been described first by Ashworth in 1869. As methods for detection expand and improve, CRC is increasingly characterized by the properties of CTCs and tumor-associated cellular elements (TACEs), such as circulating tumor DNA, cell-free DNA, and microRNA. This review serves to highlight the clinical implications of CRC CTCs and TACEs for prognostication, monitoring for disease recurrence, and response to therapy.     

Role of Circulating Tumor Cells in Metastatic Colorectal Cancer: Clinical Challenges and Opportunities

Circulating tumour cells (CTCs) have been presumed critical to the metastatic process since 1800. These epithelial cells are disseminated from the primary or metastatic tumor site and can be identified in the peripheral blood of patients. Nowadays, technical advances have rendered it easier to reproducibly and repeatedly sample this population of cells with an acceptable degree of accuracy. Therefore, these cells could become an attractive surrogate for phenotypic and genotypic markers in correlation with the development of molecular targeted therapies. In metastatic colorectal cancer several prospective studies have demonstrated the independent prognostic significance of CTCs and identified the number of CTCs before and during treatment as a predictor for overall survival and disease free survival. However, the underlying molecular characteristics of CTCs associated with outcome remain largely unknown. In this review, the role of CTCs in metastatic colorectal cancer is discussed. The variety of assays that can be used for enrichment and detection steps in CTC detection will be described and the clinical utility of these cells for assessing prognosis and monitoring response to therapy will be analyzed. We will also address the shortcomings of current detection methods that fail to identify a mesenchymal subgroup of CTCs, and briefly address how characterization of these cells can help elucidate the biology of cancer metastases.     

Correlation between Cancer Stem Cells and Circulating Tumor Cells and Their Value

Background

The scientific community has proven the value of circulating tumor cells (CTCs) as a prognostic factor in the development of cancer and progress to metastases [1, 2, 3, 4]. Simultaneously, a new type of cancer stem cell-like (CSC-like) cells has also been established as a progenitor of metastases and relapses in cancer patients [5, 6]. The present research attempts to support the hypothesis that CTCs have all the cellular hallmarks of CSC-like cells which play a crucial role in cancer spreading.

Materials and Methods

Two methods have been chosen: a cellular-based and a molecular-based method. The first method is based on the fact that CSCs form microspheres in culture. In the second method, microspheres develop in the presence of specific markers that define the CSC phenotype [6].

Results

In cellular-based assays, it has been shown that microspheres form in semi-suspension in a culture flask. In the second panel of the test, Nanog was chosen as a marker and the tested sample was positive when grown under specific conditions.

Conclusion

Our analysis has demonstrated that in this particular case, CSCs-like cells are included in the vast majority of CTCs.Key Words: Breast cancer, Cancer stem cell-like cells, Circulating tumor cells     

循环肿瘤细胞与乳腺癌患者预后相关性的Meta分析

  目的  评估循环肿瘤细胞（circulating tumor cell,CTC）在预测乳腺癌患者预后中的作用。  方法  检索Medline、Embase、中国数字化期刊全文数据库（CNKI）、万方数据库及维普全文网中国内外相关文献,收集检测外周血肿瘤细胞在乳腺癌患者预后中的研究,使用Review Manager 5.1.4中的方差倒数法对无进展生存期（progression-free survival,PFS）和总生存期（overall survival,OS）进行Meta分析。  结果  共纳入33篇英文文献,总计5 393例乳腺癌患者。Meta分析结果提示CTC阳性组较CTC阴性组在PFS [HR=2.09（95%CI:1.72~2.55）,n=23,I2=57%]和OS[HR=2.49（95%CI:2.18~2.85）,n=24,I2=0]方面差异均有统计学意义（P < 0.01）。根据UICC（International Union Against Cancer）肿瘤分期进行亚组分析,结果显示CTC对不同期别肿瘤的PFS和OS也均有预测价值（P < 0.01）。  结论  外周血CTC阳性的乳腺癌患者与CTC阴性患者相比预后较差,CTC可以作为乳腺癌患者的预后预测指标。      

肺癌循环肿瘤细胞的研究进展

转移是导致肺癌患者死亡的主要因素,积极防治转移的发生是提高患者疗效的关键.循环肿瘤细胞(CTCs)是启动远处转移的重要环节,自原发灶脱落开始即触发一系列转移级联反应,最终在远处靶器官定植和增殖.近年来,肺癌CTCs的检测技术手段不断优化,不仅可以对CTCs进行计数,还可鉴定不同亚群.肺癌CTCs检测可用于早期筛查、手术...     

肺癌循环肿瘤细胞的临床意义

循环肿瘤细胞(circulating tumor cells,CTCs)是指自发地或因诊疗操作由实体瘤或转移灶释放入血的恶性肿瘤细胞.目前,CTCs在恶性肿瘤诊断、分期、评效、治疗、预后中的意义及其富集分离、检测技术已成为研究热点.     

循环肿瘤细胞在肺癌中的研究进展

肺癌是我国发病率及死亡率最高的恶性肿瘤,其早期诊断和监测复发与转移,对提高肺癌5年生存率尤为重要循环肿瘤细胞(circulating tumor cells,CTCs)作为一种代表原发肿瘤的“液态活检标本”,有助于实时、无创性地进行组织学鉴定.CTCs检测有助于肺癌早期诊断、监测肿瘤复发与转移、判定疗效和预后,而且可能成为检测临床分子、分析耐药分子机制及解决肿瘤异质性的一种手段.本文就近年来CTCs在肺癌领域的研究进展进行综述.     

Circulating Tumor Cells in the Management of Breast Cancer

Most deaths from breast cancer are from metastatic disease. Tests that predict an individual's risk of developing metastatic disease could be useful. There is growing evidence that circulating tumor cells (CTC) could help predict recurrence and effectiveness of therapy. However, there are unresolved issues with CTC detection methods and their implementation in the community. The utility of CTC testing in the management of breast cancer is unclear based on current studies. This article reviews the role of CTC testing in the management of early and metastatic breast cancer.     

循环肿瘤细胞在肺癌中的应用

摘 要：肺癌是目前发病率和死亡率最高的恶性肿瘤,严重危害了人类的健康,转移和复发是肺癌患者死亡及治疗失败的主要原因。循环肿瘤细胞（CTCs）在肺癌的复发和转移中起重要作用,可评价患者预后、监测病情进展、评价治疗疗效、指导临床用药、体现肿瘤生物学行为,对提高肺癌患者生存率有重要作用。     

肺癌循环肿瘤细胞的研究进展

转移和复发是肺癌患者死亡的主要原因。研究发现循环肿瘤细胞(circula tingtumo rcells,CTCs)在肺癌转移和复发中起着重要作用。而且随着靶向治疗的不断进步,对于晚期无法取得肺癌实体组织的患者,CTCs作为一种肺癌组织替代物可以决定治疗方案。所以CTCs在早期发现肺癌患者的微转移、检测肿瘤复发、评估预后和选择个体化治疗方案方面有着重要作用。本文针对CTCs的研究进展及肺癌领域的应用进行综述。     

循环肿瘤细胞在肺癌中的临床研究进展

摘 要：循环肿瘤细胞（CTCs）作为“液体活检”的方法之一,在肺癌的早期检测、复发、预后评估和监测治疗反应有重要的指导作用。由于CTCs在数量上及异质性的限制,其检测方法仍有待统一的标准技术。全文对CTCs在肺癌中的检测方法和临床应用进行综述。     

结直肠癌干细胞和肿瘤微环境的相互影响及靶向策略

肠癌干细胞是结直肠癌中少量的具有恶性表型特征的未分化致瘤细胞,具有自我更新和分化克隆等独特的特征,被认为是肿瘤复发、耐药、转移的主要原因。肠癌干细胞与肿瘤微环境中各成分之间互相依存,互相影响,了解肿瘤微环境中肿瘤干细胞和其他成分之间的联系,可能对结直肠癌的治疗具有重要作用。本文就肠癌干细胞和肿瘤微环境的关系及靶向治疗进行综述。     

Circulating Tumor Cells are Associated with Bone Metastasis of Lung Cancer

Lung cancer (LC) is the leading cause of cancer mortality worldwide, predominantly due to the difficulty of early diagnosis and its high metastatic potential. Recently, increasing evidence suggests that circulating tumour cells (CTCs) are responsible for cancer metastatic relapse, and CTCs have attracted interest in cancer metastasis detection and quantification. In present study, we collected blood samples from 67 patients with bone metastasis, and 30 patients without such metastasis, and searched for CTCs. Then the association of CTC numbers with bone metastasis and other clinico-pothological variants was analyzed. Results demonstrated that when 5 or 1 was taken as a threshhold for the CTC number, there were significantly higher positivity of CTCs in the bonemetastasis group than in the non-metastasis group. While the increase in CTC number was not significantly associated with any other clinicopathological factor, including age, gender, pathological type, intrapulmonary metastasis and lymph node metastasis, the CTC number in patients with positivity of the last above mentioned variants was obviously higher than in patients with negativity of the two variants. Taken together, the CTC number appears to be significantly associated with the bone metastasis from lung cancer.