胰腺癌循环肿瘤细胞检测技术及临床应用前景

胰腺癌是消化系统高度恶性的肿瘤之一,其早期即可发生远处转移,患者生存期较短、预后较差。循环肿瘤细胞(circulating tumor cells, CTCs)是一类可进入血液循环的肿瘤细胞,不仅具有与原发肿瘤细胞相似的特征,且与肿瘤远处转移的关系更为密切。体外定量检测CTCs对胰腺癌的早期诊断、辅助分期、疗效及预后评估均具有重要意义。本文对胰腺癌CTCs富集方法及CTCs检测在胰腺癌筛查、远处转移与预后评估中的应用进行综述。     

循环肿瘤细胞在结直肠癌预后及疗效评价中的研究进展

结直肠癌（CRC）是常见的消化道肿瘤,其发病率逐年上升,复发及转移是结直肠癌患者死亡的主要原因。循环肿瘤细胞（CTCs）是起源于原发肿瘤或转移灶的完整肿瘤细胞,作为一种新型生物标志物,其存在与复发风险上升和预后不良密切相关。本文将从CTCs检测技术、CTCs应用于结直肠癌的疗效评估及预后评价等方面展开论述,以期为结直肠癌循环肿瘤细胞领域的研究提供参考。     

循环肿瘤细胞检测及其特性

肿瘤转移是导致肿瘤患者死亡的重要原因,现有影像学手段及传统肿瘤标志物不能辅助医生尽早发现肿瘤转移并判断预后。外周血循环肿瘤细胞（circulating tumor cells,CTCs）存在于肺癌、乳腺癌、前列腺癌、结直肠癌、膀胱癌和卵巢癌等多种恶性肿瘤中,     

循环肿瘤细胞在肝癌精准诊疗中的研究进展

精准医疗时代背景下的新型分子诊断技术和方法为肝癌的个体化诊疗提供了新的契机,通过检测原发或转移性肝癌自发脱落或外源因素诱导脱落进入外周血液循环系统中的肿瘤细胞,即循环肿瘤细胞(CTCs),可为肝癌的早期筛查、辅助诊断、预后判断、疗效评估和复发转移等提供重要的指导。与传统检测方法相比,CTC检测具有无创、实时、方便、高效等显著特点,有望为肝癌患者开辟一条个性化的精准治疗之路。本文将对CTC在肝癌精准诊疗中的研究进展作一概述和展望,以期为临床提供重要的参考。     

乳腺癌循环肿瘤细胞的临床应用进展

循环肿瘤细胞可能在肿瘤发生的早期侵入血液循环系统中,并在恶性肿瘤转移过程中发挥着重要作用,本文将从乳腺癌循环肿瘤细胞的富集和检测技术在临床中的应用,以及循环肿瘤细胞的遗传和分子特征进行探讨,为患者的个体化治疗提供重要依据。     

循环肿瘤DNA的临床应用及展望

<正>癌症严重威胁着人类的生命健康。中国人口众多,医疗设备及医护人员配置暂时无法与发达国家相比,大部分癌症患者在确诊时病情已经进展到中晚期,错过了最佳的治疗时机。随着医学水平的发展和提高,人们已经意识到有同样病症的患者对于同样的治疗手段的获益各异。导致患者获益效果不同的原因有多种,解决问题的关键在于以更精细的手段对癌症进行分类,针对每个     

循环肿瘤细胞的检测及其在肺癌诊疗中的应用

肺癌的高转移率和高复发率是导致肺癌患者病死率居高不下的主要原因。循环肿瘤细胞(CTCs)是存在于肿瘤患者外周血中的一类特殊细胞,可以作为肿瘤标志物用于监测肿瘤状态。CTCs检测可应用于肿瘤患者早期诊断、疗效评价、预后评估以及个体化治疗等方面。该文阐述CTCs的生物学特性,同时比较不同CTCs检测技术的原理及优缺点,探讨CTCs在肺癌临床诊疗中的应用价值。随着科学研究的不断深入,CTCs将为肺癌的诊断治疗提供新的方向。     

循环肿瘤细胞技术临床应用的前沿进展

循环肿瘤细胞(CTC)是从恶性肿瘤组织中脱落,进入外周血循环的肿瘤细胞.恶性肿瘤重要的特征之一是具有较强的转移侵袭能力,而CTC是肿瘤转移的种子,在肿瘤转移过程中起到关键作用.相比有创性组织活检,CTC检测具有非侵入性、实时性以及可以反复取样的特点,可实现无创、更灵敏的监测肿瘤动态变化,以便在治疗过程中评价治疗疗效、复...     

循环肿瘤细胞的检测与临床应用

循环肿瘤细胞(CTCs)是指由实体肿瘤原发病灶中脱落出来,进入血液循环和(或)淋巴系统的细胞,具有与原发肿瘤相似的特征,能够反映肿瘤发生发展情况并可能介导肿瘤转移.近年来,CTCs 的检测技术得到飞速发展.随着检测技术的提高,越来越多的研究发现,CTCs在多种恶性肿瘤的诊断、治疗、疗效评估和预后方面有着重要作用.     

循环肿瘤细胞的检测及临床应用

<正>恶性肿瘤目前已成为威胁全世界人民健康的主要疾病之一,肿瘤的高病死率不得不引起我们的重视,其中我国以肺癌、胃癌、直肠癌、乳腺癌、前列腺癌等高发。虽然近年来在肿瘤的诊断、治疗上已有了很大的进步,但是肿瘤的高复发、高转移率     

Circulating tumor cells as biomarkers in head and neck cancer: recent advances and future outlook

Introduction: Assessment of circulating tumor cells (CTCs) in peripheral blood from solid cancer patients including head and neck squamous cell carcinoma (HNSCC) has proven useful for detection of subclinical disease that otherwise remains invisible for current staging techniques. Based on large cohort studies, diagnostic tests for enumeration of CTCs have been developed, which can be used for tumor staging, prognosis, treatment monitoring, and post-treatment surveillance.

Areas covered: Here, we briefly summarize the history of CTC discovery. We review the current evidence of a diagnostic potential of CTCs in HNSCC. We present recent technical advancements in the tools for enrichment, detection, and molecular characterization of CTCs. We also discuss potential clinical applications of CTC detection for personalized treatment strategies.

Expert commentary: Recent technical advances in the platforms for enrichment, detection, and comprehensive molecular characterization of CTC represent a great opportunity to improve our understanding in the biology of CTCs and will allow to expand the clinical utility of CTCs in HNSCC. Especially, HNSCC patients with recurrent/metastatic disease associated dismal prognosis and little improvement in treatment outcome over the past decade might benefit in the future from incorporation of CTC assays in clinical management.     

Classifying circulating tumor cells to monitor cancer progression

Introduction: The term ‘liquid biopsy’ refers to molecular analysis of a tumor’s genetic features based on circulating genetic material in the peripheral blood derived from circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and circulating miRNAs, and has emerged as a minimally invasive tool in early cancer diagnosis and disease monitoring. CTCs are believed to originate from the primary tumor and obtain genetic heterogeneity during evolution.

Areas covered: The presence of CTCs has been associated with poor clinical outcome in patients with metastatic breast cancer, lung cancer, colorectal cancer and prostate cancer. In addition, the detection of CTCs in patients with early breast cancer has been shown to represent an independent prognostic factor associated with an unfavorable clinical outcome. Moreover, the longitudinal evaluation of CTCs in patients with early breast cancer may reveal the presence of chemo- and hormone-therapy resistant CTCs which are associated with an increased risk for disease relapse and disease-related death.

Expert commentary: The molecular characterization of CTCs may provide an important tool for the monitoring and the evaluation of treatment efficacy in patients with different tumor types such as breast, prostate, colon, and non-small cell lung cancer.     

循环肿瘤DNA检测--从发现到临床

循环肿瘤DNA检测是目前临床研究的热点,有一些标志物已在临床上开始使用,部分标志物尚处于研究发现阶段。本文主要探讨肿瘤游离DNA检测从发现到临床的过程中,临床实验室需注意的关键点,包括实验室应选择具有临床有效性和临床有用性证据的预期用途,重视检测过程的质量保证以及结果的报告和解释。     

Liquid biopsy in germ cell tumors: biology and clinical management

ABSTRACT

Introduction: Liquid biopsy is an increasingly studied approach for optimal and minimally invasive diagnostics of malignant tumors. The aim of this review is to provide evidence and discuss the utility of liquid biopsy in the management of germ cell tumors (GCTs).

Areas covered: Herein, we summarize the evidence on liquid biopsy in GCTs including serum tumor markers, circulating tumor cells, microRNA and cell-free DNA. The search of literature was conducted from Pubmed/Medline, ASCO-meeting library searching for terms ‘liquid biopsy’, ‘germ cell tumors’, ‘circulating tumor cells’, ‘microRNA’, ‘cell-free DNA’. Obtained original studies were included. Reference lists of review articles and key original articles were searched for additional original studies. We included articles published between1990 and 2019.

Expert opinion: Liquid biopsy is a minimally invasive tool using body fluids for diagnostic purposes in cancer. The established value of serum tumor markers may be already considered a liquid biopsy technique in diagnosis of GCTs. Possible near-future refinements in diagnosis of GCTs are emerging. Further information on diagnosis, prognosis and resistance is added with recently described microRNAs, circulating tumor cells and cell-free DNA. While great promise is shown, further large-scale validation is needed to incorporate these novel liquid biopsies into clinical practice.     

Liquid biopsy in the clinical management of bladder cancer: current status and future developments

ABSTRACT

Introduction: The use of liquid biopsy on the blood from solid malignancies provides a convenient way of detecting actionable mutations, monitoring treatment response, detecting early recurrence and prognosticating outcomes. The aim of this review is to discuss the current status and future direction of serum biomarkers in the clinical management of urinary bladder cancer.

Areas covered: This review provides an overview of blood liquid biopsy and bladder cancer using methods of circulating tumors cells, circulating RNA, serum metabolites and cell-free DNA. Recent clinical studies and advances in methodology are emphasized. We performed a literature search using PMC/PubMed with keywords including ‘liquid biopsy’, ‘circulating tumor DNA’, ‘cell-free DNA’, ‘biomarkers’, ‘bladder cancer’ ‘precision medicine’. Additional articles were obtained from the cited references of key articles. An emphasis was placed on recent studies published since 2018.

Expert opinion: Liquid biopsies represent a potential biomarker using cell-free DNA, metabolomic profiles of altered cellular metabolism, circulating cancer cells and RNA. Despite displaying tremendous clinical promise, the current status of the blood liquid biopsies has not reached fruition. However, future investigations should lead the evolution of liquid biomarker into clinical utility for the management of bladder cancer.     

循环肿瘤DNA检测在非小细胞肺癌早期预警及监测管理中的研究进展

非小细胞肺癌(non-small cell lung cancer,NSCLC)约占肺癌的85%,发病率和病死率位居全球前列,由于其起病与进展的隐匿性,被发现时患者已丧失最佳的治疗时机。国内外课题组致力于NSCLC早期检测技术的研发及精准化治疗方法学的探寻,以期延长患者的无进展生存期和总存活时间。液体活检即通过血液、尿液或唾液等进行疾病特异性生物学标志物检测,具有微创性、高敏感性、可重复性等优势。该手段有助于癌症基因图谱的全面反映,极大克服了病灶组织学活检在时空上的异质性,对耐药靶点的发现、新药疗效预测及临床用药方案的调整意义深远。本文就液体活检中的环肿瘤DNA(circulating tumor DNA,ctDNA)检测在NSCLC早期诊断及监测管理的研究进展进行综述,以促进该技术临床应用价值的开拓。     

应用广谱抗体CK3-6H5检测细胞角蛋白在人类上皮组织来源的肿瘤细胞系中的表达

目的 应用广谱抗细胞角蛋白（Cytokeratin,CK）抗体CK3-6H5检测上皮组织来源的肿瘤细胞系中CK的表达,并研究应用此抗体检测血液循环中此类肿瘤细胞的敏感性。方法 应用CK3-6H5标记QGY-7703等26种人类上皮组织来源的肿瘤细胞系、人Burkitt淋巴瘤细胞系Raji、人T淋巴细胞白血病细胞株Jurkat以及健康志愿者外周血单个核细胞,通过免疫荧光显色和免疫细胞化学技术检测其中CK的表达情况;以表达CK的人肝癌细胞系QGY-7703作为靶细胞,以不同的比例分别掺入到健康志愿者PBMC中,以免疫磁珠去除CD45^＋的白细胞,对肿瘤细胞进行富集,流式细胞仪检测其中CK^＋CD45^-肿瘤细胞数目,分析用CK3-6H5检测外周血循环肿瘤细胞（circulating tumor cell,CTC）的敏感性。结果 所有上皮组织来源肿瘤细胞系均表达CK,而健康志愿者和淋巴瘤细胞系Raji、T淋巴细胞白血病细胞株中未检测到CK表达。当向2×10^8个PBMC中掺入20个QGY-7703细胞时,经免疫磁珠富集后,行FACS分析,仍能检测到12个肿瘤细胞。结论 CK3-6H5抗体复合物可以识别常见的上皮来源的肿瘤,应用CK3-6H5抗体标记肿瘤细胞,采用免疫磁珠富集技术以及流式细胞技术,可以用于有效检测外周血中上皮来源的肿瘤细胞。     

Circulating tumor DNA for triple-negative breast cancer diagnosis and treatment decisions

Triple-negative breast cancer (TNBC) is a highly aggressive disease characterized by a high number of relapses and poor overall survival. The heterogeneity of the disease and the limited treatment options compared to other breast cancer subtypes mainly explain these clinical outcomes. New biomarkers are urgently needed to improve the management of TNBC. Circulating tumor DNA, identified by tumor-related molecular alterations, could be used in the context of non-invasive “liquid biopsy” and help in TNBC diagnosis and treatment decisions. In this review, we discuss the key issues related to the potential of circulating tumor DNA to improve the management of this disease and the future steps to overcome before its implementation into clinical routine within the next 5 years.     

外周血叶酸受体阳性循环肿瘤细胞检测在非小细胞肺癌筛查中的应用价值

目的观察非小细胞肺癌患者外周血叶酸受体阳性循环肿瘤细胞(circulating tumor cells,CTCs)水平变化,探讨外周血叶酸受体阳性CTCs在非小细胞肺癌筛查中的应用价值。方法非小细胞肺癌患者136例为肺癌组,肺部良性病变患者10例为良性病变组,健康志愿者54例为对照组。3组均采用以叶酸受体为靶点的免疫磁珠阴性富集+实时荧光定量PCR法检测外周血叶酸受体阳性CTCs水平;采用化学发光免疫分析法检测血清癌胚抗原(carcino-embryonic antigen,CEA)、糖链抗原(carbohydrate antigen,CA)125、CA724、细胞角蛋白19片段(cytokeratin 19fragment,CYFRA21-1)、神经元特异性烯醇化酶(neuron-specific enolase,NSE)水平。比较3组CTCs水平;比较不同临床特征非小细胞肺癌患者CTCs水平;绘制ROC曲线,评价CTCs及血清CEA、CA125、CA724、CYFRA21-1、NSE 5项指标联合诊断非小细胞肺癌的价值。结果肺癌组CTCs水平[11.21(8.58,15.30)FU/3mL]高于良性病变组[7.55(5.23,10.25)FU/3mL]和对照组[4.95(3.55,7.62)FU/3mL](P<0.05),良性病变组高于对照组(P<0.05)。TNM分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期非小细胞肺癌患者CTCs水平[11.00(8.58,13.30)、13.25(10.48,16.88)、14.77(11.47,16.55)、17.89(17.07,19.22)FU/3mL]两两比较差异均有统计学意义(H=16.443,P<0.05);不同年龄、性别、肿瘤最大径、T分期、分化等级、病理类型非小细胞肺癌患者CTCs水平比较差异均无统计学意义(P>0.05)。ROC曲线分析结果显示,CTCs以8.70FU/3mL为最佳截断值,诊断非小细胞肺癌的AUC为0.953(95%CI:0.926~0.979,P<0.05),灵敏度为79.40%,特异度为98.10%,诊断效能优于CEA、CA125、CA724、CYFRA21-1、NSE联合检测。结论非小细胞肺癌患者外周血叶酸受体阳性CTCs水平升高,且增高程度与TNM分期有关;外周血叶酸受体阳性CTCs可用于非小细胞肺癌的早期筛查。     

肿瘤患者外周血循环内皮细胞的检测及其临床意义

目的探讨循环内皮细胞（CEC）在肿瘤患者外周血中的变化及其临床意义。方法用流式细胞术检测48例健康对照者和80例肿瘤患者外周血中CEC的数量,并观察肿瘤缓解患者CEC数量的变化。结果（1）与健康对照组（2．42±1．33／μL）比较,肿瘤组CEC数量（4．38±3．52／μL）显著升高,差异有统计学意义（t=3．698,P〈0．001）;（2）肿瘤缓解组CEC数量（2．73±1．00／μL）显著低于未缓解组（4．33±2．17／μL）（t=3．488,P〈0．05）。结论CEC变化可能与肿瘤的发生、发展有密切的关系,有望作为肿瘤疗效观察的指标。