Circulating micro RNAs as diagnostic and prognostic tools for hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is an aggressive malignancy and the second leading cause of cancerrelated deaths worldwide. Conventional biomarkers exhibit poor performance in the surveillance,diagnosis,and prognosis of HCC. Micro RNAs(mi RNAs) are a class of evolutionarily conserved small non-coding RNAs that are involved in the regulation of gene expression and protein translation,and they play critical roles in cell growth,differentiation,and the development of various types of cancers,including HCC. Recent evidence revealed the role of mi RNAs as potential novel and ideal biomarkers for HCC. mi RNAs are released to extracellular spaces,and they are extremely stable in bodily fluids,including serum or plasma,where they are packaged into various microparticles or associated with RNA-binding proteins. Numerous studies have demonstrated that circulating mi RNAs have potential applications as minimally invasive biomarkers for HCC diagnosis and prognosis. The present review highlights current understanding of mi RNA biogenesis and the origins and types of circulating mi RNAs. We summarize recent progress in the use of circulating mi RNAs as diagnostic and prognostic biomarkers for HCC. We also discuss the challenges and perspectives of the clinical utility of circulating mi RNAs in HCC.     

miRNAs 与肝细胞癌发生研究进展

MicroRNAs（miRNAs）是一类长度为21～25个核苷酸的非编码小分子 RNA,参与基因转录后调控。研究发现, miRNAs 的异常表达与疾病,尤其是恶性肿瘤的发生发展密切相关。 miRNAs 在不同癌症中水平不同。研究证明,miRNAs 可以作为肝细胞癌分类、预后和早期诊断的生物学标志,并有望成为体内治疗的新靶点。本文对各类 miRNAs 小分子与肝细胞癌发生的关系,及其在临床上的应用潜能等进行了介绍。     

尾状叶肝癌的诊断与治疗进展

尾状叶肝癌是位于肝脏尾状叶的一种特殊部位的恶性肿瘤,复杂的解剖结构和较多的血管及胆管毗邻结构导致外科切除治疗困难,且病死率高。目前比较常用的治疗方法很多,包括外科手术、介入治疗、局部消融、放疗等,但是效果均较差。本文就尾状叶肝癌微创治疗的方式及理念进行了讨论。     

Novel serum microRNAs panel on the diagnostic and prognostic implications of hepatocellular carcinoma

AIM To determine a panel of serum micro RNAs(mi RNAs) that could be used as novel biomarkers for diagnosis of hepatocellular carcinoma(HCC).METHODS We initially screened 9 out of 754 serum mi RNAs by Taq Man Low Density Array in two pooled samples respectively from 35 HCC and 35 normal controls, and then validated individually by RT-qP CR in another 114 patients and 114 controls arranged in two phases. The changes of the selected mi RNAs after operation and their prognostic value were examined.RESULTS miR-375, miR-10 a, miR-122 and miR-423 were found to be significantly higher in HCC than in controls(P 0.0001), and the area under the receiver-operating-characteristic curve for the 4-miR NA panel was 0.995(95%CI: 0.985-1). All the four mi RNAs were significantly reduced after surgical removal of the tumors(P 0.0001), while still higher than normal controls(at least P 0.05)CONCLUSION The four serum miR NAs(miR-375, miR-10 a, miR-122 and miR-423) could potentially serve as novel biomarkers for the diagnostic and prognostic of HCC.     

Role of biomarkers in the prediction and diagnosis of hepatocellular carcinoma

The prevalence of hepatocellular carcinoma (HCC) has progressively increased in recent years and is now the fifth and the second most common cancer in the World and in Egypt, respectively. Much work has focused in the development of assays for detecting hepatic carcinogensis before the observance of hepatic focal lesions. Particular attention has been directed towards HCC-specific biomarkers for use in the early diagnosis of HCC and in the confirmation of radiological studies. Although a number of biomarkers have been identified, none have been considered reliable indicators of early HCC lesions. This review presents a few of the most relevant HCC biomarkers and suggests improvements to the accuracy of diagnostic assays through their combined use. Furthermore, we present an algorithm for the biomarker-based diagnosis of HCC and highlight its important role in the early prediction of HCC.     

高尔基体糖蛋白-73异常表达与肝癌诊断

高尔基体糖蛋白-73（GP73）为经糖基化修饰的膜蛋白,肝癌患者中GP73上调表达。外周血中较高水平的GP73与肝癌相关,在肝癌早期诊断方面,GP73优于AFP,是一具有较高临床诊断价值的新的肝癌标志物。     

Current biomarkers for hepatocellular carcinoma: Surveillance,diagnosis and prediction of prognosis

Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma(HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and specificity. Especially for the early detection of small HCC novel biomarkers are needed to improve the current effectiveness of screening performed byultrasound. The use of high-throughput technologies in hepatocellular research allows to identify molecules involved in the complex pathways in hepatocarcinogenesis. Several invasive and non-invasive biomarkers have been identified already and have been evaluated in different clinical settings. Gene signatures with prognostic potential have been identified by gene expression profiling from tumor tissue. However, a single "all-in-one" biomarker that fits all-surveillance, diagnosis, prediction of prognosis-has not been found so far. The future of biomarkers most probably lies in a combination of non-invasive biomarkers, imaging and clinical parameters in a surveillance setting. Molecular profiling of tumorous and non-tumorous liver tissue may allow a prediction of prognosis for the individual patient and hopefully clear the way for individual treatment approaches. This article gives an overview on current developments in biomarker research in HCC with a focus on currently available and novel biomarkers, in particular on micro RNA.     

循环microRNA作为肝细胞癌标志物的研究现状

肝细胞癌(HCC)是最常见的原发性肝癌,其高死亡率与当前对HCC的诊断和监测手段不理想密切相关。microRNA(miRNA)在HCC的发生和进展过程中发挥重要作用,其异常表达是HCC病理中的常见现象,且miRNA能被细胞释放到循环血中稳定存在。通过讨论miRNA在HCC中作用的研究进展,提出循环miRNA有望成为HCC早期诊断、监测治疗和评估预后的潜在标志物,并分析了现阶段该潜在标志物在临床验证中所面临的问题。     

肝细胞癌患者肝内病灶超声造影参数变化*

目的 探讨超声造影参数诊断肝细胞癌的应用价值。方法 2018年1月～2021年5月我院收治的HCC患者50例和乙型肝炎肝硬化患者50例,经肝穿组织病理学检查诊断,使用超声造影检查,获得病灶峰值强度(PI)、达峰时间(TTP)、渡越时间(MTT)和上升时间(RT)等参数,记录动脉期、静脉期和延迟期局部血容量和局部血流量。结果 HCC组动脉期局部血容量和局部血流量分别为(3399.7±783.7)rBV和(64.1±18.7)rBF,显著高于肝硬化组【分别为(1363.8±773.5)rBV和(41.9±10.6)rBF,P<0.05】;静脉期和延迟期局部血容量分别为(1325.8±546.3)rBV和(463.2±143.2)rBF,显著低于肝硬化组 【分别为(1775.4±541.3)rBV和(721.2±242.5)rBF,P<0.05】;HCC组病灶RT、TTP和mTT分别为(15.7±8.3)s、(22.6±5.4)s 和(133.5±92.3)s,显著低于肝硬化组【分别为(26.3±6.4)s、(32.3±7.6)s和(160.4±112.8)s,P<0.05】,而PI为(85.2±48.2)dB,显著大于肝硬化组【(31.5±3.5)dB,P<0.05】;以病理学检查诊断为金标准,超声造影定量分析检测诊断的灵敏度为92.0%,特异度为92.0%,准确度为80.0%。结论 应用超声造影定量参数诊断HCC病灶具有很高的临床价值。     

AFP阴性肝癌的肿瘤标志物诊断的研究进展

甲胎蛋白(alpha-fetoprotein,AFP)是肝细胞癌(hepatocellular carcinoma,HCC)的主要标志物,测定血清AFP水平是目前诊断HCC的主要手段.约1/3的HCC患者血清AFP水平正常,即所谓的AFP阴性肝癌,这部分患者的诊断是目前肝癌诊断中需解决的关键问题.多年来,人们一直在寻找能弥补AFP不足的肝癌标志物,以提高HCC的诊断水平.本文综述了有关AFP阴性肝癌的肿瘤标志物诊断研究进展,主要内容包括传统肝癌标志物对AFP阴性肝癌的诊断价值,新肝癌标志物对AFP阴性肝癌的诊断价值,以及对AFP阴性HCC具有潜在诊断价值的生物标志物.     

肝细胞癌早期诊断中的生物标志物

晚期肝细胞癌(HCC)患者预后通常较差,如若能早期诊断,并采取行之有效的治疗措施则可显著提高患者生存率。目前,AFP是检测HCC应用最广泛的血清标志物。然而,在一些HCC患者中并未发现AFP的升高。分析了AFP、乙型肝炎核心相关抗原、液体活检技术、微小RNA、长链非编码RNA及外泌体在HCC早期诊断中的应用潜力,通过探讨其研究进展,为HCC早期诊断方法的探索提供依据。     

Diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma （HCC） is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.     

2010年肝细胞癌处理指南更新

美国肝病学会(American Association for the Study ofLiver Diseases,AASLD)2010年7月在线发布了由Bruix和Sherman共同执笔的肝细胞癌(heaptocellular carcino-ma,HCC)监测和诊治的临床实践指南(http://www.aasld.org/practiceguidelines/Pages/NewUpdatedGuide-lines.aspx)。现翻译全文如下。序言本指南对肝细胞癌(HCC)患者的诊断、分期、治疗提供有数据支持的建议。建议来源于以下证据:     

循环microRNA早期诊断肝细胞癌研究现状及方法学探讨

肝细胞癌（HCC）是发病率和死亡率很高的恶性肿瘤,对高危人群的筛查和监测十分重要。定期检查肝脏超声和血清AFP是目前主要的筛查手段,但灵敏度和准确性仍不尽如人意。microRNA与HCC的发生、转移、复发等病理过程密切相关,相关研究也方兴未艾。循环microRNA是HCC血清学标志物中的重要成员,在HCC诊断和筛查方面具有广阔的应用前景。选择合适的microRNA和确定高效的诊断方法是相关研究的重点,更多高质量的研究还在持续进行中。     

肝脏超声造影诊断肝癌术后肝内肿瘤复发的价值探讨

目的探讨超声造影在肝癌术后肝内肿瘤复发中的诊断价值。方法48例肝癌切除术后患者经常规超声检查发现肝内直径≤2.0 cm的单发病灶患者进行超声造影检查和血清AFP检测。结果在术后平均（32.86±7.54）个月,常规超声检查发现48例肝癌术后患者肝内出现直径≤2.0 cm单发病灶,48个单发病灶呈圆形或者类圆形占位性病变,其中44个呈低回声,4个呈高回声;超声造影检查判断肿瘤复发病灶35个,良性结节13个;在32例血清AFP>200 μg/L患者,肝内肿瘤发生率为87.50%,明显高于16例血清AFP≤200 μg/L患者的43.75%,具有统计学差异（x²=10.338,P=0.001）;在48个单发病灶中,超声造影诊断正确44个（91.67%）,包括复发病灶33个和良性结节11个;超声造影对肝癌术后患者肝内直径≤2.0 cm单发病灶诊断的准确度为91.67%（44/48）,灵敏度为94.29%（33/35）,特异度为84.62%（11/13）。结论超声造影可以对肝癌术后患者肝内复发病灶进行早期诊断,对于提高患者的治疗疗效和生存期具有重要的临床意义。     

超声造影对肝细胞癌与肝转移癌的鉴别诊断价值分析

目的 研究超声造影(CEUS)检查肝转移癌(LM)与肝细胞癌(HCC)的表现特征和鉴别诊断价值。方法 2016年～2019年就诊于我院的肝脏占位患者117例,常规行CEUS检查,分析比较HCC与LM病灶在增强模式、开始增强时间、达峰时间和减退时间等方面的异同。结果 在77例HCC 患者中,有79个病灶,在40例LM患者中,有41个病灶;HCC病灶呈I型 增强为2.5%,II型为26.6%,III型为70.9%,而LM病灶分别为36.6%、9.8%和53.7%,差异显著(P＜0.05);HCC病灶增强达峰时间和减退时间分别为(29.16±7.87)s和(51.89±22.80)s,与LM病灶的【(25.98±5.30)s和(37.49±10.68)s,P＜0.05 】。结论 HCC与LM病灶在CEUS表现有一定的差异,对鉴别诊断具有很大的价值。     

肝癌患者血清microRNA-21水平变化

目的：分析不同肝病患者血清microRNA-21（miR-21）水平,以探讨miR-21对肝细胞癌（HCC）的诊断价值。方法以实时定量逆转录PCR法检测正常人、慢性乙型肝炎（CHB）、肝硬化和HCC患者（各组均为25例）血清miR-21水平,分析miR-21水平与HCC临床病理学特征的关系。结果正常人、CHB和肝硬化患者血清miR-21相对水平分别为（1.1±1.7）、（2.3±2.6）和（2.8±2.5）,而HCC患者为（22.6±4.4）,显著高于前三组（P〈0.001）;HCC患者术后1w和1m血清miR-21相对水平分别为（18.4±3.5）和（3.1±2.7）,均较术前显著降低（P＜0.001）;HCC患者血清miR-21水平与肿瘤大小、癌栓以及HBV感染相关,与肿瘤分化程度、数目和血清AFP水平无相关性。结论 miR-21在HCC患者血清中显著升高,可能作为HCC早期诊断的潜在标志。     

Exosomal microRNAs as a potential therapeutic strategy in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the fifth most com-mon cancer and the second cause of cancer-related death worldwide. The incidence of HCC is constantly increasing in correlation with the rise in diabetes and obesity, arguing for an urgent need for new developments in the treatment of this lethal cancer. Exosomes are small double-membrane vesicles loaded with distinct cargos, particularly small non-coding RNAs called microRNAs, representative of each donor cell and secreted to affect the features of neighboring cells or recipient cells located further away, like in the case of metastasis. A better understanding of the role of exosomes with a microRNA signature in cancer pathogenesis gave rise to the concept of their use as a noninvasive diagnostic biomarker and in the treatment of cancer, including HCC. In this communication, we review recent works that demonstrate that hepatic stellate cells establish an epigenetic communication with liver cancer cells, which affects their pro-malignant features. If naturally secreted patient-derived exosomes show major limitations concerning their clinical use, bio-engineered exosome mimetics that incorporate controlled components and exhibit no protumoral properties could be promising carriers for the treatment of liver cancers, which is the organ preferentially targeted by systemic injection of exosomes.