Candidate molecular markers for histological diagnosis of early hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. HCC occurs mainly in chronically diseased livers, e.g. following hepatitis B and C infection. These high-risk patients are closely followed up, and increasing numbers of small equivocal lesions are detected by imaging diagnosis. They are now widely recognized as precursor or early-stage HCCs and are classified as dysplastic nodule or early HCC. These lesions lack typical imaging and histology of ordinary HCC and do not show elevated serum markers of alpha-fetoprotein and PIVKA-II, for example. Molecular analysis of these lesions would help to develop molecular markers for objective histological diagnosis of early HCC and possibly new serum markers for early detection of HCC. It has been reported that HSP70, CAP2, glypican 3 and glutamine synthetase could serve as molecular markers for early HCC. Further analysis is expected to evaluate their usefulness in routine pathological diagnosis including biopsy diagnosis and also as serum markers for early detection of HCC.     

超声造影在早期肝癌诊断和消融术治疗中的应用研究进展

随着肝癌患病率的逐年增加,肝癌诊治的时机对患者的预后显得尤为重要,肝癌的早期诊治也得到越来越多医护人员和患者的重视。超声造影技术在肝癌患者的早期诊断、早期治疗以及消融术后疗效评估方面起到重要作用。本文就超声造影在早期肝癌诊断和消融术治疗中的临床应用进展方面予以系统综述。     

微小肝癌早期诊断关键分子的研究进展

肝癌是消化系统的常见恶性肿瘤之一，因大多数患者在肝癌早期并无临床症状，在就诊时已多是晚期，死亡率高特点决定了早期诊断和早期治疗是提高生存率最有效手段。如何提高微小肝癌的早期诊断成为我们亟待解决的重要问题，而微小肝癌早期新生血管关键分子则成为早期诊断至关重要的一步。本文通过查阅近几年国内外相关文献，对部分微小肝癌早期诊断关键分子-Prox1、Glypican-3、上皮细胞黏附因子、趋化因子受体4的研究现状和不足进行综述，旨在为微小肝癌的早期筛查和诊断提供的新方向及思路。      

Biomarkers vs imaging in the early detection of hepatocellular carcinoma and prognosis

Hepatocellular carcinoma (HCC) is the 5^th most frequently diagnosed cancer in the world, according to the World Health Organization. The incidence of HCC is between 3/100000 and 78.1/100000, with a high incidence reported in areas with viral hepatitis B and hepatitis C, thus affecting Asia and Africa predominantly. Several international clinical guidelines address HCC diagnosis and are structured according to the geographical area involved. All of these clinical guidelines, however, share a foundation of diagnosis by ultrasound surveillance and contrast imaging techniques, particularly computed tomography, magnetic resonance imaging, and sometimes contrast-enhanced ultrasound. The primary objective of this review was to systematically summarize the recent published studies on the clinical utility of serum biomarkers in the early diagnosis of HCC and for the prognosis of this disease.     

Application of CT radiomics in prediction of early recurrence in hepatocellular carcinoma

Abdominal Radiology - To appraise the ability of the computed tomography (CT) radiomics signature for prediction of early recurrence (ER) in patients with hepatocellular carcinoma (HCC). A set of...     

甲胎蛋白异质体在原发性肝癌早期诊断的临床意义

目的探讨甲胎蛋白异质体(AFP-L3)对原发性肝癌(primary hepatocellular carcinoma,PHC)早期诊断的意义。方法根据小扁豆凝集素对甲胎蛋白(AFP)的亲和力不同,采用亲和免疫电泳印迹法检测52例原发性肝癌和57例良性肝病患者的AFP-L3的血清含量;以AFP-L3>15%作为PHC阳性的诊断标准。结果PHC患者的AFP-L3阳性率明显高于良性肝病组,差别有统计学意义(P<0.01);PHC患者的AFP-L3阳性率与AFP水平无正相关。AFP≤400μg/L和>400μg/L的PHC病例,AFP-L3阳性率分别是76.9%和84.6%,AFP-L3含量与血清AFP浓度无关;AFP含量与癌肿直径大小呈正相关(r=0.453,P<0.01)。在癌肿直径>2 cm的PHC病例,AFP-L3阳性率与癌肿直径无相关性(r=0.012,P>0.05)。结论AFP-L3对于低水平AFP的PHC,尤其是小肝癌的诊断具有重要的临床意义。     

Fibrolamellar hepatocellular carcinoma

Fibrolamellar hepatocellular carcinoma is a primary malignant tumor of the liver that usually affects adolescents and young adults. If detected early, this cancer is frequently resectable, with a much longer survival time than in classic hepatocellular carcinoma. Fibrolamellar hepatocellular carcinoma has distinct radiographic and pathologic features. Serum unsaturated vitamin B12 binding capacity and plasma neurotensin may be used as tumor markers.     

Danazol-induced hepatocellular carcinoma

Sir, Danazol, an inhibitor of pituitary gonadotropin with weak androgeniceffects, is currently used in the treatment of endometriosis,hereditary angio-oedema, systemic lupus erythematosus, and idiopathicthrombocytopenic purpura (ITP). Its hepatological side-effectshave been well documented. These include reversible elevationsof serum aminotransferase values,¹ cholestatic hepatitis,² hepaticpeliosis³ and hepatocellular adenomas.⁴ Only a few     

血清热休克蛋白90早期诊断肝细胞癌的价值

目的 探讨血清热休克蛋白90(HSP90)在肝细胞癌(HCC)早期诊断中的价值.方法 检测240例HCC患者血清HSP90及甲胎蛋白(AFP)水平.采用受试者工作特征(ROC)曲线评估HSP90和AFP对HCC的敏感性.结果 HSP90诊断HCC的敏感性和特异性分别为89.38％和42.86％,而血清AFP诊断HCC的...     

Screening serum biomarkers for early primary hepatocellular carcinoma using a phage display technique

Hepatocellular carcinoma (HCC) occurs mainly in chronically diseased livers following hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Early detection and diagnosis of HCC would be of great clinical benefit. In this study, we used a random phage display peptide library and sera from early-stage primary HCC patients (n = 30) to screen potential serum biomarkers for early primary HCC. Age- and sex-matched patients with HBV and/or HCV infection were used as controls. In the screening phase, 19 out of 20 randomly selected phage clones exhibited specific reaction with purified sera IgG from early primary HCC patients, among them 14 coming from the same phage clone with inserted peptidesequence RGWCRPLPKGEG (named HC1). In the validation phase, phage ELISA results showed that the positive reaction rate of the HC1 phage clone was 91.4% with the early HCC group (n = 70), significantly higher than that with the HBV infection group (20.0%) (n = 70), the HCV infection group (12.9%) (n = 70), the HBV + HCV infection group (24.3%) (n = 70), the cirrhosis group (17.1%) (n = 70), and the healthy control group (10.0%) (n = 70). In conclusion, the HC1 mimic peptide showed high diagnostic validity for early primary HCC, and thereby could be a candidate serum biomarker for early primary HCC.     

预测肝癌微血管侵犯及早期复发的临床研究

目的探讨预测肝癌患者微血管侵犯的因素,并探讨影响肝癌患者术后早期复发的因素。方法回顾性分析147例肝癌根治性切除患者的临床病理特征。其中,有微血管侵犯的患者93例(甲组),无微血管侵犯的患者54例(乙组)。单因素及多因素分析预测微血管侵犯及早期复发的因素,随访患者术后无瘤生存期,分析预测术后早期复发的因素,ROC曲线评价预测微血管侵犯和预测术后早期复发的因素。结果 Logistic回归分析提示肿瘤直径是预测肝癌微血管侵犯的独立因素;ROC曲线下面积为0.823,肿瘤直径越大越容易出现微血管侵犯(P<0.001)。Cox回归分析提示肿瘤大体分型、微血管侵犯是预测肝癌患者术后早期复发(<2年)的独立因素,ROC曲线下面积分别为0.695,0.727。肿瘤大体分型级别越高或存在微血管侵犯的患者,手术后易早期复发(P<0.001)。结论术前明确肿瘤分型,预测肝癌微血管侵犯可以推测患者预后,并对术后治疗有一定的指导作用。     

肝癌自发性破裂早期死亡的危险因素分析及治疗

目的 探讨影响肝癌自发性破裂早期死亡的危险因素以及有效的治疗方法.方法 回顾性分析1998年1月至2008年1月我院收治的34例肝癌自发性破裂患者的临床资料,分析18项临床、病理等指标对患者30 d内病死率的影响.结果 13例(38%,13/34)在治疗后30 d内死亡.单因素分析显示肝硬化、Child C级、休克、输血、甲胎蛋白(AFP)、ALP及AST与早期死亡有关,多因素分析显示休克是早期死亡的独立危险因素.8例行急诊肝切除,中位生存时间14.4个月,1、3年生存率分别为63%(5/8)和13%(1/8).26例急诊止血成功后有5例行二期肝切除,中位生存时间为44.4个月,1、3年生存率分别为80%(4/5)和60%(3/5).结论 肝脏储备功能差、肿瘤恶性程度高及出血量大提示肝癌自发性破裂患者预后差,休克及输血是影响早期死亡的独立危险因素.肝切除术具有确切的疗效,止血成功后二期肝切除更加安全合理.     

利用芯片技术筛选肝癌早期复发密切相关的microRNA

目的:应用miRNA芯片技术筛选肝癌早期复发密切相关的miRNA,为进一步深入探讨miRNA在介导肝癌高侵袭性及术后早期复发中的作用打下基础。方法:从本院肝癌标本库中选取10例肝癌患者进入本研究,其中早期复发组(术后第1年出现肝内复发病灶)和非早期复发组(术后2年以上未出现肝癌复发或转移)各5例,抽提总RNA并分离出小分子RNA进行Cy3荧光标记,将标记的小分子RNA与miRNA芯片进行杂交反应,分析差异表达的miRNA。结果:相对于非早期复发组,早期复发组肿瘤标本中有miR-602、miR-451、miR-144和miR-486-5p等4个miRNAs表达显著上调(上调倍数>2.0);有miR-551b、miR-96和miR-502-3p等3个miRNAs表达显著下调(下调倍数<0.5)。结论:筛选得到肝癌早期复发的miRNA差异表达谱,其可能与肝癌的早期复发发生发展有关。     

Biomarkers: evaluation of clinical utility in surveillance and early diagnosis for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of death from cancer worldwide. Strategies to surveil and diagnose HCC in an earlier stage are urgently needed since this is when curable interventions can be offered to achieve long-term disease-free survival. Over the past few decades, research has suggested measuring alpha-fetoprotein (AFP) concentration and performing abdominal ultrasound (US) as part of routine surveillance of HCC every 6 months for high-risk patients, and many HCC guidelines worldwide have also recommended these examinations. Over the past 5 years, however, the role of serum biomarkers in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by some Western countries. In Asian countries, serum biomarkers such as AFP, the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) are still recommended for HCC surveillance and are being used as an adjunctive diagnostic tool in accordance with HCC guidelines. Moreover, novel biomarkers including Dickkopf-1 (DKK1), midkine (MDK), and microRNA (miRNA) are being studied in this regard. China accounts for 50% of HCC cases worldwide, so identifying biomarkers of HCC is paramount. Recent studies have indicated the clinical utility of simultaneous measurement of AFP and DCP for the early detection of HCC in China. They are predominantly used for cases caused by HBV infection. Additional large-scale prospective studies should be conducted to establish the utility of these biomarkers.     

Metastasis-related miR-185 is a potential prognostic biomarker for hepatocellular carcinoma in early stage

We previously reported that miR-185 is associated with hepatocellular carcinoma (HCC) venous metastasis analysed by miRNA-array profile. The aim of this study is to further investigate the clinicopathological significance and prognostic value of miR-185 in early stage HCC. We classified 95 patients with early stage HCC into treated recurrence group (TR) and none treated recurrence group (NTR), and detected the miR-185 expression levels in TR and NTR groups. We found that low miR-185 expression correlated with more tumor recurrence (37/46), while high miR-185 level led to lower recurrence rate (17/49) (P < 0.05). There was no direct relationship between miR-185 and clinicopathological features, including age, gender, ALT, AFP, liver cirrhosis, tumor size, tumor encapsulation, tumor differentiation (P > 0.05). Kaplan–Meier analysis showed that low miR-185 group had a remarkable lower survival rate and shorter time to recurrence than high miR-185 group (P < 0.05). Univariate and multivariate analysis, using Cox's proportional hazards model, also indicated that low miR-185 expression was a sensitive prognostic factor for survival and recurrence in early stage HCC (P < 0.05). We upregulated or downregulated miR-185 expression by transfected miR-185 mimics or inhibitor into HCC cell lines, and observed the influence of miR-185 on HCC cells in vitro. Our results manifested that miR-185 could suppress the tumor cell growth and invasive ability (P < 0.05). Therefore, miR-185 might be an effective and sensitive biomarker of HCC in early stage, and the upregulation of miR-185 might be considered to be a potentially important molecular treatment strategy for patients with HCC.     

Immunotherapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, with over a million new cases annually. It is generally advanced upon detection due to underlying liver disease, which further complicates treatment. Most of the therapeutic strategies in current use (surgery, transplantation, irradiation or chemotherapy) are either palliative or only of benefit to a small percentage of patients. This article reviews the biology of HCC, including many of the molecular changes and mechanisms leading to HCC development. This article discusses the recent innovative strategies to interfere with the progression of HCC, including novel gene therapy strategies. The most recent data supporting the use of immunotherapy for hepatocellular cancer is reviewed in detail.     

Immunotherapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, with over a million new cases annually. It is generally advanced upon detection due to underlying liver disease, which further complicates treatment. Most of the therapeutic strategies in current use (surgery, transplantation, irradiation or chemotherapy) are either palliative or only of benefit to a small percentage of patients. This article reviews the biology of HCC, including many of the molecular changes and mechanisms leading to HCC development. This article discusses the recent innovative strategies to interfere with the progression of HCC, including novel gene therapy strategies. The most recent data supporting the use of immunotherapy for hepatocellular cancer is reviewed in detail.     

乙型肝炎病毒相关早期肝细胞癌影像学

早期肝细胞癌(eHCC)病理诊断标准已建立并于2009年更新,但目前国内外均未确定eHCC影像学诊断标准。中华医学会放射学分会传染病学组联合中国医师协会放射医师分会感染影像专业委员会、中国研究型医院学会感染与炎症放射学专业委员会、中国性病艾滋病防治协会感染(传染病)影像工作委员会、中国医院协会传染病分会传染病影像学组和北京影像诊疗技术创新联盟组织国内10余省市40多名专家共同努力形成本共识,旨在为相关专业医生诊断eHCC提供帮助。