OBJECTIVE: To explore the diagnostic value of the serum metabolites identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A total of 126 patients admitted to Tianjin Third Central Hospital were enrolled, including 27 patients with HBV-related hepatitis with negative viral DNA (DNA-N), 24 with HBV-related hepatitis with positive viral DNA, 24 with HBV-related liver cirrhosis, 27 with HBV-related HCC undergoing surgeries or radiofrequency ablation, and 24 with HBV-related HCC receiving interventional therapy, with 25 healthy volunteers as the normal control group. Serum samples were collected from all the subjects for HPLC/MS analysis, and the data were pretreated to establish an orthogonal partial least- squares discriminant analysis (OPLS-DA) model. The differential serum metabolites were preliminarily screened by comparisons between the HBV groups and the control group, and the characteristic metabolites were identified according to the results of non-parametric test. The potential clinical values of these characteristic metabolites were evaluated using receiver operator characteristic curve (ROC) analysis. RESULTS: A total of 25 characteristic metabolites were identified in the HBV- infected patients, including 9 lysophosphatidylcholines, 2 fatty acids, 17α-estradiol, sphinganine, 5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8 metabolites with few reports. The patients with HBV- related HCC showed 22 differential serum metabolites compared with the control group, 4 differential metabolites compared with patients with HBV-related liver cirrhosis; 10 differential metabolites were identified in patients with HBV-related HCC receiving interventional therapy compared with those receiving surgical resection or radiofrequency ablation. From the normal control group to HBV-related HCC treated by interventional therapy, many metabolites underwent variations following a similar pattern. CONCLUSIONS We identified 25 characteristic metabolites in patients with HBV-related HCC, and these metabolites may have potential clinical values in the diagnosis of HBV-related HCC. The continuous change of some of these metabolites may indicate the possibility of tumorigenesis, and some may also have indications for the choice of surgical approach.
Carcinoma, Hepatocellular ; blood ; diagnosis ; virology ; Case-Control Studies ; Chromatography, High Pressure Liquid ; DNA, Viral ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; virology ; Humans ; Liver Cirrhosis ; virology ; Liver Neoplasms ; blood ; diagnosis ; virology ; Mass Spectrometry ; Metabolome ; Metabolomics ; ROC Curve

OBJECTIVETo assess the value of detecting peripheral blood circulating tumor cells (CTCs) in the diagnosis and treatment of hepatocellular carcinoma (HCC).

METHODSA total of 296 patients diagnosed with HCC admitted in our department from July 2013 to January 2015 were analyzed, with 39 patients with benign liver disease serving as the control group. The distribution of CTCs in the peripheral blood of HCC patients were detected by CanPatrol(TM) CTCs, and its relationship with the clinical features and prognosis of the patients were analyzed.

RESULTSs CTCs were detected in 64.5% (191/296) of the HCC patients but in none of the control group (P<0.05). Positive CTCs in peripheral blood of HCC patients were significantly correlated with serum AFP level, tumor number, TNM stage, BCLC stage, portal vein tumor thrombus and metastasis (P<0.05). In 127 HCC patients receiving radical surgery, the patients positive for CTCs showed significantly shorter relapse-free survival time (P<0.05).

CONCLUSIONPositive CTCs in the peripheral blood may indicate a poor prognosis in HCC patients. CTCs may serve as a indicator for monitoring the prognosis of HCC.

Carcinoma, Hepatocellular ; blood ; diagnosis ; Case-Control Studies ; Humans ; Liver Neoplasms ; blood ; diagnosis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Portal Vein ; pathology ; Prognosis

Precision medicine is becoming the goal of translational research on colorectal cancer. Accurate molecular subtyping contributes to better guidance of clinical practice. The current TNM staging system of colorectal cancer is inadequate in terms of guiding clinical practice, such as the underestimation of prognosis of with stage II( and III( colorectal cancer TNM staging, and identification of high-risk and low-risk patients with stage II( colorectal cancer. Researchers from Europe and US have proposed a number of molecular subtypings with clinicopathological phenotypes and molecular phenotypes, which has certain practical significance and is beneficial to the choice of treatment regimen and targeted drugs. But the current results of subtyping research require further validations by clinical large scale multi-center trials. Based on precision medicine, molecular subtyping gradually reveals its clinical significance and is optimized through combining genomics with various clinical phenotypes, indicating its guidance for clinical practice, which is the inevitable course of precision medicine accomplishment. In recent years, there have been many new advances in colorectal cancer liver metastasis treatment. The prognosis of colorectal cancer patients undergoing resection of liver metastasis lesion is similar to those with stage III(. Early recurrence within 6 months after translational treatment and resection occurred in about one third of the patients with initially unresectable liver metastasis, and the overall survival was poor. Thus, an evaluation system should be established in order to avoid the strong therapy and strive for better quality of life in some patients. Individualized treatment for colorectal cancer is emphasized increasingly. Body fluid (peripheral blood and urine) marker detection is a recent research hotspot, including serum protein(polypeptide), plasma miRNA, circulating tumor cells and circulating nucleic acid.
Biomarkers, Tumor ; blood ; urine ; Colorectal Neoplasms ; diagnosis ; pathology ; therapy ; Humans ; Liver Neoplasms ; secondary ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Precision Medicine ; Prognosis ; Quality of Life ; Translational Medical Research

BACKGROUND/AIMS: The aim of this study was to evaluate the feasibility of alpha-fetoprotein (AFP) as a diagnostic tool for hepatocellular carcinoma (HCC) in Korean patients. METHODS: We retrospectively reviewed the medical records of HCC and cirrhosis patients at three hospitals. For each HCC patient, a cirrhosis patient matched for age, sex, etiology, and Child-Pugh classification was selected by simple random sampling. The performance of AFP in the diagnosis of HCC was determined using receiver operating characteristic curve analysis. RESULTS: A total of 732 patients with HCC or cirrhosis were selected for each case and the control groups. The mean age was 54 years, and 72.4% of patients were male. The mean serum AFP levels in the HCC group and cirrhosis group were 3,315.6 and 117.2 ng/mL, respectively (p < 0.001). The area under the receiver operating characteristic curve for all HCC patients was 0.757. The sensitivity, specificity, and positive predictive value of AFP was 50.55%, 87.70%, and 80.43%, respectively, at a cut-off of 20 ng/mL; 37.70%, 95.90%, and 90.20%, respectively, at a cut-off of 100 ng/mL, and 30.05%, 97.27%, and 91.67%, respectively, at a cut-off of 200 ng/mL. A cut-off of 100 ng/mL was more sensitive than one of 200 ng/mL with equivalent specificity and positive predictive value. CONCLUSIONS: The cut-off AFP value for early-stage HCC was 17.4 ng/mL. Our study cautiously suggests that AFP has a role in the diagnosis of HCC, and that the appropriate value of AFP for the diagnosis of HCC may be 100 ng/mL rather than 200 ng/mL.
Aged ; Area Under Curve ; Carcinoma, Hepatocellular/*blood/*diagnosis/pathology ; Feasibility Studies ; Female ; Humans ; Liver Neoplasms/*blood/*diagnosis/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Predictive Value of Tests ; ROC Curve ; Republic of Korea ; Retrospective Studies ; alpha-Fetoproteins/*analysis

Undifferentiated embryonal sarcoma of the liver (UESL) is rare primary hepatic sarcoma and is known to occur in pediatric patients. This case is the UESL occurred in a 51-year old male patient. Multilocular cystic lesion was composed of primitive spindle cells without specific differentiation. This rare case would help to review differential diagnosis of primary sarcoma in liver and cystic neoplasm of the liver.
Abdomen/diagnostic imaging ; Biomarkers, Tumor/blood ; Desmin/metabolism ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Liver Neoplasms/blood/*pathology/surgery ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Vimentin/metabolism

BACKGROUND/AIMS: Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. METHODS: We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve. RESULTS: Plasma GPC3 levels in HCC patients were very low (0–3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729. CONCLUSION: The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted.
Aged ; Aged, 80 and over ; Area Under Curve ; Biomarkers, Tumor/blood ; Carcinoma, Hepatocellular/*diagnosis/pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Glypicans/*blood ; Humans ; Liver Neoplasms/*diagnosis/pathology ; Male ; Neoplasm Staging ; ROC Curve ; alpha-Fetoproteins/*analysis

OBJECTIVETo screen and identify serum biomarkers for childhood hepatoblastoma (HB).

METHODSThe serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins.

RESULTSAfter SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group.

CONCLUSIONSApo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.

Apolipoprotein A-I ; blood ; genetics ; Biomarkers ; blood ; Child, Preschool ; Early Detection of Cancer ; Female ; Hepatoblastoma ; blood ; diagnosis ; Humans ; Infant ; Liver Neoplasms ; blood ; diagnosis ; Male ; Real-Time Polymerase Chain Reaction ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

OBJECTIVEThe purpose of this study was to compare MRI findings of solitary hypovascular hepatic nodules, benign and malignant, to identify their MRI characteristics.

METHODSWe retrospectively assessed solitary hypovascular hepatic nodules ≤ 3 cm in 135 patients, among them there were 55 malignant nodules [29 peripheral nodules of cholangiocarcinoma, PCC, and 26 hepatic metastases, HM] and 80 benign nodules [48 inflammatory myofibroblastic tumors, IMT, and 32 hepatic hemangioma, HG], proved by surgery, biopsy or follow-up imaging. Unenhanced and dynamic enhanced MRI findings of the 135 patients were analyzed retrospectively. Statistical analysis included Chi-square test or Fisher's exact test, and receiver operating characteristic (ROC) curve.

RESULTSThere was significant difference (P < 0.05) between the malignant group and benign group in terms of location, margin, T2WI signal intensity, heterogeneity or homogeneity of the nodule, and type and degree of peritumoral and intratumoral enhancement. Area under the curve at the first film reading by three radiologists was 0.678 ± 0.047, 0.920 ± 0.022 at the second time, and there was a significant difference (Z = 5.22, P < 0.05) between them.

CONCLUSIONSOur data indicated that solitary hypovascular hepatic nodules show unenhanced and dynamic enhanced MRI features. Therefore, MR imaging combined with clinical and biochemical data does provide reliable information for a proper diagnosis of such hepatic lesions and differentiation of malignant from benign nodules.

Cholangiocarcinoma ; pathology ; Diagnosis, Differential ; Hemangioma ; pathology ; Humans ; Liver ; blood supply ; pathology ; Liver Neoplasms ; blood supply ; pathology ; Magnetic Resonance Imaging ; ROC Curve ; Retrospective Studies

PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/beta-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p<0.001). The optimum DKK-1 cutoff level was 1.01 ng/mL (AUC=0.829; sensitivity 90.7%; specificity 62.0%). Although DKK-1 had a higher AUC than alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) (AUC=0.829 vs. 0.794 and 0.815, respectively), they were statistically similar (all p>0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.
Area Under Curve ; Biomarkers/blood/metabolism ; Biomarkers, Tumor/blood ; Carcinoma, Hepatocellular/blood/*diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/*blood/*metabolism ; Liver Neoplasms/blood/*diagnosis ; Male ; Middle Aged ; Protein Precursors/blood/metabolism ; Prothrombin/metabolism ; ROC Curve ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; alpha-Fetoproteins/analysis/metabolism

Primary colorectal choriocarcinoma is a rare neoplasm. Only 19 cases have been reported worldwide, most of which involved adenocarcinomas. The prognosis is usually poor, and the standard therapy for this tumor has not been established. A 61-year-old woman presented with constipation and lower abdominal discomfort. She was diagnosed with primary adenocarcinoma with focal choriocarcinomatous differentiation in the sigmoid colon and liver metastasis. Because the serum beta-human chorionic gonadotropin level was not significantly elevated, and because only focal choriocarcinomatous differentiation was diagnosed, we selected the chemotherapy regimen that is used for the treatment of metastatic colorectal adenocarcinoma. The patient survived for 13 months after the initial diagnosis. This is the first case in Korea to assess the suppressive effects of the standard chemotherapy for colorectal adenocarcinoma against coexisting colorectal choriocarcinoma and adenocarcinoma.
Adenocarcinoma/*diagnosis/drug therapy/pathology ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; CA-19-9 Antigen/analysis ; Chorionic Gonadotropin, beta Subunit, Human/blood ; Colon, Sigmoid/pathology ; Colonic Neoplasms/*diagnosis/drug therapy/pathology ; Colonoscopy ; Constipation/etiology ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Liver Neoplasms/secondary ; Middle Aged ; Organoplatinum Compounds/therapeutic use ; Prognosis ; Tomography, X-Ray Computed