Diagnostic Tool For Hepatocellular Carcinoma Research Articles

Significance of Serum Biomarkers in Early Diagnosis of Hepatocellular Carcinoma in Patients with Fisher Groups

Introduction: This study investigates the relationship between serum biomarkers and the detection of hepatocellular carcinoma (HCC) in different fisher groups in Bangladesh. The research adopts a descriptive and experimental approach to demonstrate the health risks faced by fishermen, including tobacco consumption, polluted drinking water, and insufficient sunlight exposure. Method: We used serum biomarkers such as vitamin D, alpha-fetoprotein (AFP), creatinine (Cr), and hemoglobin A1C (HbA1c) to evaluate their significance in distinguishing between different categories and sexes. Result: We determined a strong and direct correlation between insufficient vitamin D levels and an increased risk of liver cancer. The combination of AFP, vitamin D, and Cr (AFP+Vit-D+Cr) emerges as a highly predictive tool, enhancing diagnostic accuracy and providing a reliable means of identifying hepatocellular carcinoma. Conclusion: The identified correlation showed the significance of addressing lifestyle factors and promoting nutritional support to mitigate the risk of liver cancer among fisher groups. The AFP+Vit-D+Cr combination is a promising diagnostic tool for hepatocellular carcinoma, offering an improved early detection and intervention approach.

Galad Score as a Prognostic Marker for Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for more than 75% of primary liver cancers, which are the second leading cause of cancer-related deaths. The GALAD (gender, age, AFP-L3, AFP, and des-carboxy-prothrombin) score is a diagnostic tool developed based on gender, age, alpha-fetoprotein, alpha-fetoprotein L3, and des-gamma-carboxy prothrombin, originally designed as a diagnostic tool for HCC in high-risk patients. We analyzed 212 patients with and without cirrhosis. The population study was divided into patients with liver cirrhosis without evidence of HCC at the time of serum sample collection for GALAD score determination and patients with liver cirrhosis and a confirmed diagnosis of HCC at the time of serum sample collection for GALAD score determination. Patients were followed up until death or liver transplantation. The association between variables and HCC mortality risk was performed, and the results were presented as hazard ratio (HR). The receiver operating characteristic (ROC) curve was used to assess the performance of the GALAD HCC diagnosis. The survival probability was explored using the non-parametric test, and the equality of survival amongst categories was assessed with the log-rank test. Biomarkers were higher in the HCC group compared to cirrhosis. Kaplan-Meier survival probability analysis for individual GALAD categories revealed that a high GALAD level was associated with decreased survival during follow-up, and the difference between the curves was statistically significant (p = 0.01). Our findings suggest that the GALAD score has promise as a prognostic tool, with implications for improving patient management and treatment strategies for HCC.

Investigating Up-to-Seven Criteria and APRI (AST Platelet Ratio) as Prognostic Factors in Intermediate-Stage Hepatocellular Carcinoma Patients Who Received Transarterial Chemoembolization.

Transarterial chemoembolization (TACE) is one of the locoregional treatments for intermediate-stage hepatocellular carcinoma (HCC). Multidetector computed tomography (MDCT) is a widely used diagnostic tool for HCC. It can also evaluate tumor size, tumor number, and tumor invasion. This study aimed to determine the median survival time in intermediate-stage HCC patients who underwent TACE and to find out prognostic factors influencing patients' survival time after TACE. A computerized search of medical record database in Maharaj Nakorn ChiangMai Hospital from January 2016 to December 2019 revealed 187 intermediate-stage HCC patients who received TACE as the first-line treatment. The median survival time of patients in this study was 9.9 months (95% CI: 8.3-11.6). The patients with aspartate aminotransferase-to-platelet ratio (APRI) less than 0.5 had a significantly better median survival time as compared with patients with APRI ratio more than 0.5; (13.2 months versus 9.9 months, p-value < 0.05). Univariate and multivariate Cox regression analysis demonstrated that tumor number > 7 and tumor size > 5 centimeters (cm) could be considered as independent parameters predicting poor overall survival time in the sufferers (HR 2.64 95%CI 1.68-4.15 and HR 2.38 95%CI 1.32-4.31, respectively). Based on our findings, patients with intermediate-stage HCC who received TACE had a lower median survival time compared to previous studies. However, we identified APRI less than 0.5, tumor size less than 5 cm, and tumor number less than 7 as prognostic factors improving survival time in intermediate-stage HCC patients.

Exosomal microRNA panel as a diagnostic biomarker in patients with hepatocellular carcinoma.

Background: Diagnostic tools for hepatocellular carcinoma (HCC) are critical for patient treatment and prognosis. Thus, this study explored the diagnostic value of the exosomal microRNA panel for HCC. Methods: Expression profiles of microRNAs in exosomes and plasma of HCC and control groups were assessed using microRNA microarray analysis. Reverse transcription-quantitative PCR was applied to evaluate the expression of candidate microRNAs in blood samples from 50 HCC patients, 50 hepatic cirrhosis patients, and 50 healthy subjects. The area calculated the diagnostic accuracy of the microRNAs and microRNA panel under the receiver operating characteristic curve (AUC). Results: MicroRNA microarray analysis revealed that there were more differentially expressed microRNAs in the exosome HCC group than plasma HCC group. Among the 43 differentially expressed microRNAs contained in both exosomes and plasma, we finally decided to testify the expression and diagnostic significance of microRNA-26a, microRNA-29c, and microRNA-199a. The results indicated that expression of the microRNA-26a, microRNA-29c, and microRNA-199a in both exosomes and plasma was significantly lower in HCC patients compared with hepatic cirrhosis and healthy group. Interestingly, exosomal microRNAs were substantially more accurate in diagnosing HCC than microRNAs and alpha-fetoprotein in plasma. Moreover, the exosomal microRNA panel containing microRNA-26a, microRNA-29c, and microRNA-199a showed high accuracy in discriminating HCC from healthy (AUC = 0.994; sensitivity 100%; specificity 96%) and hepatic cirrhosis group (AUC = 0.965; sensitivity 92%; specificity 90%). Conclusion: This study revealed that the exosomal microRNA panel has high accuracy in diagnosing HCC and has important clinical significance.

Salivary orosomucoid 1 as a biomarker of hepatitis B associated hepatocellular carcinoma

Saliva is rich in proteins, DNA, RNA and microorganisms, and can be regarded as a biomarker library. In order to explore a noninvasive and simple means of early screening for liver cancer, proteomics was used to screen salivary markers of hepatitis B associated liver cancer. We used mass spectrometry coupled isobaric tags for relative and absolute quantitation (iTRAQ)-technology to identify differentially expressed proteins (DEPs). Western blot, immunohistochemistry and enzyme linked immunosorbent assay were used to detect marker expression of in tissues and saliva. Statistical analysis was used to analyze the diagnostic efficacy of the markers was analyzed through statistical analyses. By comparing the hepatocellular carcinoma (HCC) group with non-HCC groups, we screened out 152 salivary DEPs. We found orosomucoid 1(ORM1) had significantly higher expression in saliva of HCC patients compared with non-HCC groups (p < 0.001) and the expression of ORM1 in liver cancer tissues was significantly higher than that in adjacent normal tissues (p < 0.001). The combination of salivary ORM1 and alpha-fetoprotein (AFP) showed reasonable specificities and sensitivities for detecting HCC. In a word, salivary ORM1 as a new biomarker of hepatitis B associated hepatocellular carcinoma, combination of salivary ORM1 and AFP as an improved diagnostic tool for hepatocellular carcinoma.

Prognostic value of preoperative protein-induced vitamin K absence or antagonist II after liver resection for hepatitis B-related hepatocellular carcinoma: a nationwide multicenter study.

Although protein-induced vitamin K absence or antagonist II (PIVKA-II) has been used as a diagnostic tool for hepatocellular carcinoma (HCC), its prognostic value remains unclear. This was a nationwide multicenter study using the database of the Korean Liver Cancer Association. Patients with hepatitis B-related HCC who underwent liver resection as the first treatment after initial diagnosis (2008-2014) were selected randomly. Propensity score matching (1:1) was performed for comparative analysis between those with low and high preoperative PIVKA-II. Univariable and multivariable Cox proportional-hazards regression were used to identify prognostic factors for HCC-specific survival. Among 6,770 patients, 956 patients were included in this study. After propensity score matching, the 2 groups (n = 245, each) were well balanced. The HCC-specific 5-year survival rate was 80.9% in the low PIVKA-II group and 78.7% in the high PIVKA-II group (P = 0.605). In univariable analysis, high PIVKA-II (>106.0 mAU/mL) was not a significant predictor for worse HCC-specific survival (hazard ratio [HR], 1.183; 95% confidence interval [CI], 0.76-1.85; P = 0.461). In multivariable analysis, hyponatremia of <135 mEq/L (HR, 4.855; 95% CI, 1.67-14.12; P = 0.004), preoperative ascites (HR, 4.072; 95% CI, 1.59-10.43; P = 0.003), microvascular invasion (HR, 3.112; 95% CI, 1.69-5.74; P < 0.001), and largest tumor size of ≥5.0 cm (HR, 2.665; 95% CI, 1.65-4.31; P < 0.001), but not preoperative high PIVKA-II, were independent predictors for worse HCC-specific survival. Preoperative PIVKA-II is not an independent prognostic factor for HCC-specific survival after liver resection for hepatitis B-related HCC.

Circulating Long and Circular Noncoding RNA as Non-Invasive Diagnostic Tools of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide, partially due to late diagnosis of the disease. Growing evidence in the field of biomarker discovery has shown the promising use of nucleic acid in the early detection of many cancers, including HCC. Here, we review data on how various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) could be used as a diagnostic tool for HCC being differentially expressed in HCC compared to non-HCC patients. These non-coding RNAs (ncRNAs) showed high stability in the blood being present as free-circulating molecules or encapsulated into exosomes. This review reports some recent evidence on the use of lncRNAs and circRNAs as possible diagnostic biomarkers for HCC. Further, their pathophysiological mechanism in liver carcinogenesis was also described, elucidating the complex regulatory networks making these ncRNAs of particular relevance for the study of liver malignancy cancer.

HCC and Tumor Biomarkers: Does One Size Fits All?

Hepatocellular carcinoma (HCC) is a highly malignant disease and early diagnosis rates remain to be unsatisfactory. Owing to this limitation, advances in treatment options including liver transplantation (LT) are limited to improve survival. Recent HCC guidelines no longer recommend alpha-fetoprotein (AFP) as a surveillance and diagnostic tool for HCC. Hence, utilization of novel biomarkers has become imperative to improve disease management strategies. Noninvasive, serum-based biomarkers are potential options to aid early diagnosis as well as prompting treatment. However, further studies are required to find out the accuracy and potential of these approaches and introduce into clinical practice.

Golgi Protein 73 as a Diagnostic Tool for Hepatocellular Carcinoma in Cirrhotic Hepatitis C Patients

Background and study aim: Hepatocellular carcinoma (HCC) is the commonest primary liver cancer originating from the hepatocytes. HCC nowadays considered the 3rd cause of malignancy related mortality allover the world. Small HCC, means that size of hepatic focal lesions did not exceed 5 centimeters in patients with solitary hepatoma, typically have no clinical manifestations. This makes cirrhotic liver patients a perfect target population for HCC surveillance.This study was designed to evaluate the clinical use of serum GP73 levels as a good diagnostic biomarkers for malignant liver tumours in cirrhotic patients due to HCV infection. Subjects and Methods: The study was designed as a Descriptive - Analytic study at Suez Canal University Hospital. The study included 87 individuals who were divided into four groups (healthy, chronic hepatitis, cirrhosis and HCC patients). All patients were clinically evaluated, had routine laboratory investigations and measurements of circulating levels of AFP and GP73. Abdominal ultrasonography and Triphasic CT abdomen was done for detection of hepatic focal lesions and hepatobiliary system. Results: The maximum cutoff levels for GP73 was 534.5 ng/L and in comparison the cutoff AFP level was 32 ng/mL. For GP73, the sensitivity was 88% and specificity 88% while the sensitivity of AFP was 72% and the specificity of AFP was 80%. The +v predictive value of GP73 and the -ve predictive value of GP73 were 84.6% and 87.5% while the same values of AFP were 75% and 73.1%, respectively. Conclusion: It was found that serum GP73 was up-regulated in HCC and we can use it as a good biomarker for early detection and for screening of malignant liver lesions in cirrhotic patients due chronic HCV infection and it would be more accurate and effective tool than serum AFP in discriminating the malignant liver lesion from the chronic hepatitis.

Serum Clusterin as a Diagnostic Tool for HCV Related Hepatocellular Carcinoma

AbstractBackground: Hepatocellular carcinoma (HCC) is consid-ered one of the major malignant tumors in the world. The number of cases increases every years and HCC almost always has a fulminant course with grave prognosis.Aim of Study: Was to evaluate the clinical use of serum clusterin levels as a diagnostic tool for HCC with hepatitis C virus related cirrhosis.Subjects and Methods: A total of 100 subjects, 80 patients and 20 healthy controls were enrolled in this study. Patients were divided into 2 groups; group I: (30 patients) with HCV related liver cirrhosis, group II: (50 patients) with hepatocel-lular carcinoma. Serum levels of alpha fetoprotein (AFP) and clusterin (CLU) were measured. Alpha fetoprotein based on Chemiluminescent microparticle immunoassay (CMIA). Serum CLU concentration was performed using enzyme linked immunosorbent assay technique (ELISA).Results: The mean values of serum clusterin increase significantly among HCC patients than controls and cirrhotic patients. The cirrhotic patients show significant decrease than controls group. The sensitivity and specificity for clusterin was 72.5% and 92% and for AFP was 77.3% and 100%, respectively. The AUC for clusterin was 0.8 (p<0.001) com-pared with 0.9 (p<0.001) for AFP. The combined parallel approach improved the diagnostic sensitivity to 96.5%. We found positive correlation between AFP and sCLU (r=0.31 and p=0.003).Conclusion: Serum CLU levels should be a useful potential biomarker for HCC diagnosis.

Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major public health problem worldwide. Hepatocarcinogenesis is a complex multistep process at molecular, cellular, and histologic levels with key alterations that can be revealed by noninvasive imaging modalities. Therefore, imaging techniques play pivotal roles in the detection, characterization, staging, surveillance, and prognosis evaluation of HCC. Currently, ultrasound is the first-line imaging modality for screening and surveillance purposes. While based on conclusive enhancement patterns comprising arterial phase hyperenhancement and portal venous and/or delayed phase wash-out, contrast enhanced dynamic computed tomography and magnetic resonance imaging (MRI) are the diagnostic tools for HCC without requirements for histopathologic confirmation. Functional MRI techniques, including diffusion-weighted imaging, MRI with hepatobiliary contrast agents, perfusion imaging, and magnetic resonance elastography, show promise in providing further important information regarding tumor biological behaviors. In addition, evaluation of tumor imaging characteristics, including nodule size, margin, number, vascular invasion, and growth patterns, allows preoperative prediction of tumor microvascular invasion and patient prognosis. Therefore, the aim of this article is to review the current state-of-the-art and recent advances in the comprehensive noninvasive imaging evaluation of HCC. We also provide the basic key concepts of HCC development and an overview of the current practice guidelines.

Investigating the breath metabolome as a diagnostic tool for hepatocellular carcinoma in cirrhotic patients

Background: Non-invasive diagnostic testing for hepatocellular carcinoma in cirrhotic patients is attractive since cirrhotic patients often exhibit marginal renal function and coagulopathy which complicates their ability to undergo imaging with contrast medium and/or needle biopsy. Selective ion flow tube mass spectrometry (SIFT-MS) is a non-invasive test that can be used to identify trace gases in human breath. This study investigated the level of volatile organic compounds (VOCs) in cirrhosis patients and evaluated the difference of VOCs according to the presence of hepatocellular carcinoma (HCC). Methods: Cirrhotic patients without HCC (n = 22) and with HCC (n = 57) were included in this study. Cirrhosis and HCC were diagnosed based on imaging studies or biopsy. Clinical characteristics were compared between the groups using Fisher's exact and the Mann–Whitney test. Analysis of covariance (ANCOVA) was used to estimate age and gender adjusted average VOC levels between the two groups. Receiver operating characteristic (ROC) analysis was performed to assess discriminatory ability of VOCs. Results: Baseline characteristics were similar between the groups. Median age was significantly higher in HCC group (67 yo vs 58 yo, p < 0.001). In ANCOVA analysis, the mean breath concentrations of 3 VOCs (acetone, isoprene and pentane) were significantly lower in HCC group (all p < 0.05). The ROC analyses were performed in those 3 VOCs and an area under the curve of acetone, isoprene and pentane were 0.841 (95%CI: 0.752–0.929), 0.789 (95%CI: 0.691, 0.886), and 0.828 (95%CI: 0.734–0.922), respectively. Conclusion: Breath metabolome analysis could be a potential non-invasive diagnostic tool for HCC in cirrhotic patients. This observation warrants further investigation in larger cohorts.

Circulating microRNA\u2019s as a diagnostic tool for hepatocellular carcinoma in a hyper endemic HIV setting, KwaZulu-Natal, South Africa: a case control study protocol focusing on viral etiology

BackgroundA wide range of studies has investigated the diagnostic proficiency of extracellular microRNAs (miRNAs) in hepatocellular cancer (HCC). HCC is expected to increase in Sub-Saharan Africa (SSA), due to endemic levels of viral infection (HBV/HIV), ageing and changing lifestyles. This unique aetiological background provides an opportunity for investigating potentially novel circulating miRNAs as biomarkers for HCC in a prospective study in South Africa.MethodsThis study will recruit HCC patients from two South African cancer hospitals, situated in Durban and Pietermaritzburg in the province of KwaZulu-Natal. These cases will include both HBV mono-infected and HBV/HIV co-infected HCC cases. The control group will consist of two (2) age and sex-matched healthy population controls per HCC case randomly selected from a Durban based laboratory. The controls will exclude patients if they have any evidence of chronic liver disease. A standardised reporting approach will be adopted to detect, quantify and normalize the level of circulating miRNAs in the blood sera of HCC cases and their controls. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) will be employed to quantity extracellular miRNAs. Differences in concentration of relevant miRNA by case/control status will be assessed using the Wilcoxon rank-sum (Mann-Whitney U) test. Adjustment for multiple testing (Bonferroni correction), receiver operating curves (ROC) and optimal breakpoint analyses will be employed to identify potential thresholds for the differentiation of miRNA levels of HCC cases and their controls.DiscussionAlthough there is a growing base of literature regarding the role of circulating miRNAs as biomarkers, this promising field remains a ‘work in progress’. The aetiology of HBV infection in HCC is well understood, as well as it’s role in miRNA deregulation, however, the mediating role of HIV infection is unknown. HCC incidence in SSA, including South Africa, is expected to increase significantly in the next decade. A combination of factors, therefore, offers a unique opportunity to identify candidate circulating miRNAs as potential biomarkers for HBV/HIV infected HCC.

Value of contrast enhanced ultrasound in evaluation of small hepatomas: a case series review

Purpose: Contrast enhanced ultrasound (CEUS) is currently well recognised as an imaging modality for evaluation of hepatic lesions. There are various published guidelines which have recognised its use as a definitive diagnostic tool for hepatocellular carcinoma (HCC) in high risk patients.

Hepatic B cell leukemia-3 suppresses chemically-induced hepatocarcinogenesis in mice through altered MAPK and NF-κB activation.

The transcriptional nuclear factor kappa B (NF-κB)-coactivator B cell leukemia-3 (Bcl-3) is a molecular regulator of cell death and proliferation. Bcl-3 has been shown to be widely expressed in different cancer types including hepatocellular carcinoma (HCC). Its influence on hepatocarcinogenesis is still undetermined. To examine the role of Bcl-3 in hepatocarcinogenesis mice with hepatocyte-specific overexpression of Bcl-3 (Bcl-3Hep) were exposed to diethylnitrosamine (DEN) and phenobarbital (PB). Hepatic Bcl-3 overexpression attenuated DEN/PB-induced hepatocarcinogenesis. Bcl-3Hep mice exhibited a lower number and smaller tumor nodules in response to DEN/PB at 40 weeks of age. Reduced HCC formation was accompanied by a lower rate of cell proliferation and a distinct expression pattern of growth and differentiation-related genes. Activation of c-Jun N-terminal kinase (JNK) and especially extracellular-signal regulated kinase (ERK) was reduced in tumor and tumor-surrounding liver tissue of Bcl-3Hep mice, while p38 and NF-κB p65 were phosphorylated to a higher extent compared to the wild type. In parallel, the absolute number of intrahepatic macrophages, CD8+ T cells and activated B cells was reduced in DEN/PB-treated Bcl-3Hep mice mirroring a reduction of tumor-associated inflammation. Interestingly, at the early time point of 7 weeks following tumor initiation, a higher rate of apoptotic cell death was observed in Bcl-3Hep mice. In summary, hepatocyte-restricted Bcl-3 overexpression reduced hepatocarcinogenesis related to prolonged liver injury early after tumor initiation likely due to decreased survival of DEN/PB-damaged, premalignant cells. Therefore, Bcl-3 could become a novel player in the development of therapeutic and diagnostic tools for HCC.

Value of quantitative and qualitative analyses of circulating cell-free DNA as diagnostic tools for hepatocellular carcinoma: a meta-analysis.

Qualitative and quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of hepatocellular carcinoma (HCC). Many studies have evaluated these approaches, but the results have been variable. This meta-analysis is the first to synthesize these published results and evaluate the use of circulating cfDNA values for HCC diagnosis. All articles that met our inclusion criteria were assessed using QUADAS guidelines after the literature research. We also investigated 3 subgroups in this meta-analysis: qualitative analysis of abnormal concentrations of circulating cfDNA; qualitative analysis of single-gene methylation alterations; and multiple analyses combined with alpha-fetoprotein (AFP). Statistical analyses were performed using the software Stata 12.0. We synthesized these published results and calculated accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratios [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence intervals [95% CIs]). Data were pooled using bivariate generalized linear mixed model. Furthermore, summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize overall test performance. Heterogeneity and publication bias were also examined. A total of 2424 subjects included 1280 HCC patients in 22 studies were recruited in this meta-analysis. Pooled sensitivity and specificity, PLR, NLR, DOR, AUC, and CIs of quantitative analysis were 0.741 (95% CI: 0.610-0.840), 0.851 (95% CI: 0.718-0.927), 4.970 (95% CI: 2.694-9.169), 0.304 (95% CI: 0.205-0.451), 16.347 (95% CI: 8.250-32.388), and 0.86 (95% CI: 0.83-0.89), respectively. For qualitative analysis, the values were 0.538 (95% CI: 0.401-0.669), 0.944 (95% CI: 0.889-0.972), 9.545 (95% CI: 5.298-17.196), 0.490 (95% CI: 0.372-0.646), 19.491 (95% CI: 10.458-36.329), and 0.87 (95% CI: 0.84-0.90), respectively. After combining with AFP assay, the values were 0.818 (95% CI: 0.676-0.906), 0.960 (95% CI: 0.873-0.988), 20.195 (95% CI: 5.973-68.282), 0.190 (95% CI: 0.100-0.359), 106.270 (95% CI: 22.317-506.055), and 0.96 (95% CI: 0.94-0.97), respectively. The results in this meta-analysis suggest that circulating cfDNA have potential value for HCC diagnosis. However, it would not be recommended for using independently, which is based on the nonrobust results. After combining with AFP, the diagnostic performance will be improved. Further investigation with more data is needed.

Mass spectrometry-based serum peptide profiling in hepatocellular carcinoma with bone metastasis

To investigate the potential of serum peptides as a diagnostic tool for hepatocellular carcinoma (HCC) with bone metastasis. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) was used to characterize the serum peptide profile of HCC patients with bone metastasis. Serum samples from 138 HCC patients (66 cases with and 72 cases without bone metastasis) were randomly assigned into a training set (n = 76) and a test set (n = 62). Differential serum peptides were examined using ClinProt magnetic bead-based purification followed by MALDI-TOF-MS. The sequences of differentially expressed serum peptides were identified using liquid chromatography-mass spectrometry. A diagnostic model was established using a learning algorithm of radial basis function neural network verified by a single blind trial. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of the established model. Ten peptide peaks were significantly different between HCC patients with or without bone metastasis (P < 0.001). Sequences of seven peptides with mass to charge ratios (m/z) of 1780.7, 1866.5, 2131.6, 2880.4, 1532.4, 2489.8, and 2234.3 were successfully identified. These seven peptides were derived from alpha-fetoprotein, prothrombin, serglycin, isoform 2 of inter-alpha-trypsin inhibitor heavy chain H4, isoform 1 of autophagy-related protein 16-2, and transthyretin and fibrinogen beta chains, respectively. The recognition rate and predictive power of a diagnostic model established on the basis of six significant peptides (m/z for these six peptides were 1535.4, 1780.7, 1866.5, 2131.6, 2880.4, and 2901.9) were 89.47% and 82.89%, respectively. The sensitivity and specificity of this model based upon a single blind trial were 85.29% and 85.71%, respectively. ROC analysis found that the AUC (area under the ROC curve) value was 0.911. Our study suggested that serum peptides may serve as a diagnosis tool for HCC bone metastasis.

Circulating microRNA-122a as a diagnostic marker for hepatocellular carcinoma

BackgroundThe purpose of this study was to evaluate the potential value of circulating miRNA-122a and miRNA-221 in the diagnosis of hepatocellular carcinoma.MethodsSerum samples were obtained from 85 patients with hepatocellular carcinoma and 85 age-matched and sex-matched healthy volunteers. miRNAs were isolated from the serum samples, and alfa-fetoprotein levels were determined. Expression of miRNA-122a and miRNA-221 in cases and controls was quantified using U6 sn RNA as the internal control. The diagnostic value of miRNA-122a, miRNA-221, and alfa-fetoprotein was compared by receiver operating characteristic analysis.ResultsThe serum miRNA-122a level in patients with hepatocellular carcinoma was significantly reduced in comparison with healthy controls and correlated with known risk factors for hepatocellular carcinoma. Circulating miRNA-221 in patients with hepatocellular carcinoma was higher compared with the control group, but the difference was not statistically significant. Receiver operating characteristic analysis revealed that the diagnostic power of miRNA-122a was suboptimal compared with serum alfa-fetoprotein. Further, the serum alfa-fetoprotein and miRNA-122a combined classifier resulted in performance similar to that of alfa-fetoprotein alone.ConclusionThe serum miRNA-122a level correlates with risk factors for hepatocellular carcinoma. However, use of miRNA-122a as a diagnostic tool for hepatocellular carcinoma is not superior to alfa-fetoprotein. Further analysis is needed to evaluate the diagnostic power of plasma miRNA-122a for hepatocellular carcinoma.

Prognostic value of α-fetoprotein and des-γ-carboxy prothrombin responses in patients with hepatocellular carcinoma treated with transarterial chemoembolization

Background/AimsAlpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) have been used as diagnostic tools for hepatocellular carcinoma (HCC). However, prediction of outcome using AFP and DCP has not been elucidated. We investigated the clinical role of AFP and DCP as predictors of treatment outcome in patients with HCC undergoing trans-arterial chemoembolization (TACE).MethodsBetween January 2003 and December 2005, we enrolled 115 treatment-naïve patients who received TACE as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 50% from the baseline level 1 month after TACE. Patients with AFP < 20 ng/mL or DCP < 20 mAU/mL were excluded.ResultsThe median age was 59 years and the male gender predominated (n = 81, 70.4%). AFP and DCP response was identified in 91 (79.1%) and 77 (66.9%) patients after TACE. Although progression-free survival (PFS) did not differ according to AFP response (P = 0.150), AFP responders showed significantly better overall survival (OS) than non-responders (34.9 vs. 13.2 months; P = 0.002). In contrast, DCP response did not influence either PFS or OS (all P > 0.05). Multivariate analyses showed that gamma-glutamyltranspeptidase and baseline AFP were predictors of PFS (all P < 0.05) and that male gender, the presence of liver cirrhosis, baseline DCP, number of measurable tumors and AFP response were independent predictors of OS (all P < 0.05).ConclusionsAFP response and higher baseline DCP level are significant predictors of OS in treatment-naïve patients with HCC receiving TACE who showed pretreatment elevation of both AFP and DCP.

Dickkopf-1 and hepatocellular carcinoma

e410 www.thelancet.com/oncology Vol 13 October 2012 evidence exists to suggest that DKK1 was better than AFP for diagnosis of hepatocellular carcinoma of 5 cm or smaller. Finally, Shen and colleagues did not assess hepatocellular carcinoma related to hepatitis C virus infection, heavy alcohol consumption, cholangio carcinoma, or metastatic cancer. More studies are needed before DKK1 can be accepted as a diagnostic tool for hepatocellular carcinoma.