Serum ferritin in hepatocellular carcinoma

The serum ferritin level was detected by radioimmunoassay in 142 patients with hepatocellular carcinoma (HCC). Serum ferritin level was raised (greater than ng/ml) in 38% (54/142) of patients with HCC. There was no difference in serum ferritin levels between stages 1, 2 and 3 HCC. None of the 4 patients with stage 1 HCC had serum ferritin levels above 300 ng/ml. In this small group of patients, measurement of serum ferritin was not a satisfactory indicator of stage 1 HCC. A combination of serum ferritin alpha fetoprotein (AFP) measurements may be useful for a rising suspicion of HCC. We found that a correct diagnosis of HCC was made in 38% (54/142) of patients by measurement of ferritin alone, and in 83.8% (119/142) by measurement of AFP alone, but in 92.3% (131/142) by measurement of a combination of these two markers. Serum ferritin estimation may be helpful in detection of HCC without elevated AFP. Among 12 cases of HCC with serum AFP less than 500 ng/ml, 6 cases (50%) had serum ferritin levels greater than ng/ml. There was no correlation between serum ferritin and AFP, nor between serum ferritin and HBsAg. However, among 12 patients with very high ferritin levels (range 992-3000 ng/ml), 11 (91.7%) had AFP levels of more than 500 ng/ml (mean = 4800 ng/ml, range 500-32000 ng/ml).     

Specific molecular markers in hepatocellular carcinoma

BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost importance. Circulating diagnostic and prognostic biomarkers could be used in proper postoperative treatment of patients at an early stage of HCC development. This review summarizes recent studies of the specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An English-language literature search was conducted using MEDLINE (June 1998 to September 2006) on researches of some valuable specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma tissues can synthesize various tumor-related proteins, polypeptides, and isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early diagnostic and prognostic biomarkers could predict the development and metastases of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP subfraction, transforming growth factor (TGF)-β1, HS-GGT, and free insulin-like growth factor (IGF)-Ⅱ may be more specific markers than total AFP level for early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF-β1-mRNA, IGF-Ⅱ-mRNA, etc from peripheral blood mononuclear cells of HCC patients have been most extensively used in monitoring distal metastasis or postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and secrete valuable molecular markers into blood. The analyses of circulating hepatoma-specific biomarkers are usefulto early diagnosis of HCC or monitoring metastasis or postoperative recurrence of HCC.     

The prognostic molecular markers in hepatocellular carcinoma

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.     

Serum tumor markers in patients with hepatocellular carcinoma: diagnosis of alpha-fetoprotein -low or -negative patients

The presence of specific gamma-glutamyl transpeptidase isoenzyme (gamma-GTPI) and variant alkaline phosphatase (VAALP) were concurrently determined, and levels of basic fetoprotein (BFP) and carcinoembryonic antigen (CEA) in addition to alpha-fetoprotein (AFP) were measured in 144 hepatocellular carcinoma (HCC) patients in order to evaluate the diagnostic value of these tumor markers with respect to AFP-low or -negative patients and the tumor stage. Serum AFP levels below 400 ng/ml, commonly seen in sera of hepatobiliary diseases other than HCC, were noted in 42% of the patients. The diagnostic usefulness was increased by combination assay of these markers except for CEA. A definitive diagnosis of HCC could be made in 78% of the patients by a combination of gamma-GTPI, VAALP and AFP. Moreover, a diagnosis of malignancy could be made in 87% of cases by the inclusion of BFP. The prevalence of BFP and CEA increased in proportion to the tumor stage, whereas that of AFP and gamma-GTPI were independent of stage and were high even in patients in comparatively early stages. Furthermore, secreting type markers such as AFP and gamma-GTPI were relatively useful for diagnosis of HCC when the lesions were still small.     

肝细胞癌肿瘤标志物的研究进展

肿瘤标志物检测是目前协助诊断、监测肝细胞癌(HCC)及评估预后的重要方法之一。总结了肿瘤标志物对HCC的诊断、预测肿瘤生物学特性及预后等方面的价值,以及多项肿瘤标志物联合诊断的价值。新的肿瘤标志物不断被发现,有助于提高HCC的早期诊断率和评估治疗效果。     

肝癌早期诊断分子标志物的研究进展

腹部超声、CT、数字减影血管造影的检查，虽能发现肝癌(HCC)，但对监测单个癌细胞较难。肝癌诊断特异蛋白及相关基因分析，有助于肝癌诊断、疗效观察、术后随访、复发或转移监测。     

Serum manganese superoxide dismutase and thioredoxin are potential prognostic markers for hepatitis C virus-related hepatocellular carcinoma

AIM:To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus(HCV)related hepatocellular carcinoma(HCC).METHODS:Sixty-four consecutive patients who were admitted to Kagoshima University Medical and Dental Hospital were enrolled in this retrospective study.All patients had chronic liver disease(CLD) due to infection with HCV.Thirty patients with HCV-related HCC,34 with HCV-related CLD without HCC(non-HCC),and 20 healthy volunteers(HVs) were enrolled.Possible associa...     

Serum N-acetylglucosaminyltransferase III activities in hepatocellular carcinoma

N-Acetylglucosaminyltransferase III (GnT III) catalyses the addition of N-acetylglucosamine through a β 1–4 linkage to the mannose of the trimannosyl core, resulting in conversion of the concanavalin A (Con A)-reactive glycan into a non-reactive state. In this study, we measured GnT III activity to evaluate its diagnostic efficacy and its therapeutic effect on hepatocellular carcinoma (HCC). Concanavalin A-non-reactive fraction of serum transferrin (Tf) was also determined since the sugar chains of Tf are one of the possible candidates for the product of GnT III. Serum samples (159) were used from patients with HCC (89), liver cirrhosis (30), chronic hepatitis (19), alpha-fetoprotein (AFP) producing gastric carcinoma metastatic to the liver (five) and healthy controls (16). N-Acetyl-glucosaminyltransferase III activity was determined by high performance liquid chromatography. The reactivity of serum Tf to Con A was also analysed in 21 paired HCC samples before and after treatment by crossed immuno-affinoelectrophoresis. N-Acetylglucosaminyltransferase III activity from the HCC group (153 ± 72 pmol/mL/h) was significantly higher than that from liver cirrhosis (99 ± 67 pmol/mL per h), chronic hepatitis (84 ± 39pmol/mL per h) and the normal controls (62 ± 16pmol/mL per h). N-Acetylgiucosaminyltransferase III activity of 21 patients with HCC was significantly reduced after treatment such as transcatheter arterial chemoembolization and/or percutaneous ethanol infection therapy, (123 ± 77 to 100 ± 60pmol/mL per h). Commensurate decreases of AFP and des-γ-carboxy prothrombin with GnT III activity were also observed after treatment. The Con A-non-reactive fraction (n= 21; 6.4 ± 2.3%) in patients with HCC after treatment was significantly lower than before (8.2 ± 2.4%). The present study suggests that GnT III activity is a possible and in the diagnosis and evaluation of HCC, especially when other tumour markers are negative.     

基因标志物在肝癌诊断中的临床价值

肝癌的发生与肝炎病毒感染、致癌物作用、癌基因或癌相关基因激活、抗癌基因失活或胚胎期某些癌基因重新复活等诸多因素有关，并经启动、促进、演变多阶段的发病过程。临床匕肝癌确诊时已多属中、晚期，缺乏有效治疗，术后易复发及远处转移，预后较差，早诊断、早治疗至关重要。早期诊断和术后复发监测仍是临床研究的重点。[第一段]     

肝癌早期诊断标志物研究进展

肝癌 (HCC)是我国常见的恶性肿瘤 ,其死亡率位于第二位。所有HCC几乎都有肝硬化基础 ,确诊时已多属中、晚期 ,缺乏有效治疗 ,预后差。虽HCC非手术疗法有进展 ,但手术切除仍是目前最有效的治疗方法[1 ,2 ] 。晚期HCC切除后复发率高 ,易转移 ,早期诊断极为重要。肝癌血清标志物众多 ,尚无单一标志物能够诊断所有肝癌。敏感而特异如甲胎蛋白AFP L3、异常凝血酶原 (PIVKA Ⅱ )、肝癌特异性GGT等标志物 ,它们间无相关性并起互补作用。肝癌标志物分析有助于肝癌早期诊断、疗效观察及术后随访、复发或转移监测[3 ] 。本文就早期诊断有价…