Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.
Humans ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/pathology* ; Prognosis ; Carnosine ; alpha-Fetoproteins/metabolism* ; Biomarkers, Tumor/genetics* ; Liver Cirrhosis/diagnosis* ; ROC Curve

OBJECTIVETo study the expressions of β-catenin in hepatocellular carcinoma (HCC) tissue, adjacent cirrhotic liver tissue and hemangioma-surrounding liver tissue to understand whether their difference in expression will influence on the prognosis and to study the relationship between Wnt/β-catenin signaling pathway and HNF-1α expression.

METHODS50 specimens of HCC, 50 specimens of adjacent cirrhotic liver tissue and 7 specimens of hemangioma-surrounding liver tissue were used to detect the differences in the expression of β-catenin and HNF-1α in them by immunohistochemistry.

RESULTSThe expression rate of β-catenin was 74.0% (37/50) in the HCC tissue, 18.0% (9/50) in cirrhotic liver tissue, and 14.3% (1/7) in hemangioma-surrounding liver tissue. The expression rate of β-catenin in HCC tissue was significantly higher than that in the hemangioma-surrounding liver tissue (P = 0.002) and cirrhotic liver tissue (P < 0.001). The patients with abnormal expression had worse prognosis. Among the 50 HCC cases, the expression of HNF-1α was negative in 20.0% (10/50), weak positive in 40.0% (20/50), moderately positive in 26.0% (13/50), and strong positive in 14.0% (7/50). Among the 50 adjacent cirrhotic liver tissues, the expression of HNF-1α was negative in 12.0% (6/50), weak positive in 20.0% (10/50), moderately positive in 52.0% (26/50) and strong positive in 16.0% (8/50). In the 7 cases of hemangioma-surrounding liver tissue, the expression of HNF-1α was negative in 0(0/7), weak positive in 14.3% (1/7), moderately positive in 28.6% (2/7) and strong positive in 57.1% (4/7). The positive expression rate of HNF-1α in the HCC tissue was significantly lower than that in the hemangioma-surrounding liver tissues (P = 0.029) and adjacent cirrhotic liver tissues (P = 0.008). The patients with positive HNF-1α expression had a better prognosis. The abnormal expression of β-catenin was negatively correlated with positive HNF-1α expression (r = -0.673, P < 0.001).

CONCLUSIONSThe occurrence and development of HCC is related to the abnormal β-catenin expression. There is a negative correlation between Wnt/β-catenin signaling pathway and HNF-1α expression.

Carcinoma, Hepatocellular ; diagnosis ; metabolism ; Hemangioma ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Liver Neoplasms ; diagnosis ; metabolism ; Prognosis ; beta Catenin ; genetics ; metabolism

OBJECTIVETo investigate the expression of IFITM3 in colorectal carcinoma and its clinical significance.

METHODS213 patients with colon ademocarcinoma and 214 patients with colon adenoma treated by surgery in our hospital from March 2008 to June 2010 were included in this study. The levels of IFITM3 in normal colon nucosa, adenoma, and adenocarcinoma tissues were detected by real-time PCR and immunochemistry, and its relationship with metastasis and prognosis in 213 colorectal cancer patients was analyzed.

RESULTSThe IFITM3 mRNA level in metastatic tumor group was 18.37 ± 0.61, significantly higher than that in the normal 4.49 ± 0.69 and non-metastases groups (7.32 ± 0.76; F = 460.380, P < 0.001). The positive rate of IFITM3 protein expression in metastatic tumor group (69.0%) was significantly higher than that in the normal (3.9%), non-metastasies groups (19.0%) and adenoma groups (11.3%). Our clinical analysis confirmed that the IFITM3 expression was associated with peritumoral invasion, hepatic metastases, metastases of para-colonic lymph nodes, mesocolonic lymph nodes and mesenteric root lymph nodes, omental metastasis and AJCC classification (P < 0.05). Furthermore, the survival curve analysis showed that patients with lower IFITM3 level expression had a higher 5-year survival rate (88.8%) than that in the patients with higher expression (40.2%, P < 0.001).

CONCLUSIONSIFITM3 expression has a positive correlation with metastasis and prognosis in patients with colorectal carcinoma.

Adenocarcinoma ; diagnosis ; metabolism ; Adenoma ; Colorectal Neoplasms ; diagnosis ; metabolism ; Humans ; Liver Neoplasms ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Neoplasms ; Peritoneal Neoplasms ; Prognosis ; RNA, Messenger ; RNA-Binding Proteins ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction ; Survival Analysis ; Survival Rate

OBJECTIVETo investigate the expression of special AT-rich sequence binding protein 1 (SATB1) mRNA in hepatocellular carcinoma (HCC) and explore its correlation to the clinicopathological features, surgical outcomes and metastasis of HCC.

METHODSThe total RNA was extracted from 102 HCC tissues and the adjacent tissues, and the expression of SATB1 mRNA was detected using quantitative real-time PCR. The correlations of SATB1 mRNA expression to the clinicopathological features, postoperative recurrence and metastasis of the tumor were analyzed.

RESULTSThe expression of SATB1 mRNA in HCC tissues was 3.27 folds higher than that in the adjacent tissues (P<0.001). The expression of SATB1 mRNA in HCC was associated with liver cirrhosis, AFP level, tumor size, tumor thrombi, histological differentiation, TNM classification, postoperative recurrence and metastasis (P<0.05), but not to the patients' gender, age, HbsAg positivity, HCV-Ab positivity, tumor number, or the presence of tumor encapsulation (P>0.05). In patients with significant high expression, high expression, and low expression of SATB1 mRNA, the postoperative recurrence rates were 82.68%, 0, and 0, with the 3-year survival rate of 0, 52.63%, and 100%, respectively.

CONCLUSIONSATB1 mRNA expression is associated with the postoperative recurrence and metastasis of HCC, and can be used as an indicator for predicting the recurrence and metastasis of HCC.

Aged ; Carcinoma, Hepatocellular ; genetics ; metabolism ; Female ; Humans ; Liver Neoplasms ; genetics ; metabolism ; Male ; Matrix Attachment Region Binding Proteins ; genetics ; metabolism ; Middle Aged ; Neoplasm Metastasis ; diagnosis ; Neoplasm Recurrence, Local ; diagnosis ; RNA, Messenger ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction ; methods

Human carboxylesterase 1 (HCE1), belonging to a multigene serine hydrolase family, is a major liver carboxylesterase responsible for the hydrolysis and metabolism of various xenobiotics. It also plays an important role in the transportation and metabolism of endogenous cholesterol ester and free fatty acid, and is closely associated with the pathogenesis of hepatocellular carcinoma. This review describes current developments in the molecular structure, the roles in drug, toxins and lipid metabolism, and the early diagnosis for hepatocellular carcinoma of human carboxylesterase 1.
Carboxylic Ester Hydrolases ; genetics ; physiology ; Carcinoma, Hepatocellular ; diagnosis ; Cholesterol Esters ; metabolism ; Fatty Acids, Nonesterified ; metabolism ; Humans ; Liver Neoplasms ; diagnosis ; Xenobiotics ; metabolism

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.
Adenoma/*diagnosis/surgery ; Carcinoma, Hepatocellular/diagnosis ; Diagnosis, Differential ; Focal Nodular Hyperplasia/*diagnosis/surgery ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnosis/surgery ; beta Catenin/genetics/metabolism

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.
Adenoma/*diagnosis/surgery ; Carcinoma, Hepatocellular/diagnosis ; Diagnosis, Differential ; Focal Nodular Hyperplasia/*diagnosis/surgery ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnosis/surgery ; beta Catenin/genetics/metabolism

BACKGROUND/AIMS: The investigation of a specific tumor marker for hepatocellular carcinoma (HCC) is needed to examine the carcinogenesis and to select the patients for treatment options. The aim of this study was to find the genes related to HCC. We also examined the expression level of these genes in cancer cell lines and tissue specimens. METHODS: Three pairs of HCC tissue and non-neoplastic hepatic tissue around the HCC were collected from three patients who underwent resection for HCC. Differential display reverse transcriptase-PCR (DD RT-PCR) using GeneFishing (TM) PCR was used to detect the differences in the gene expression between in HCC tissue and non-neoplatic tissue. Up- or down-regulated genes in HCC tissue were identified through BLAST searches after cloning and sequencing assays. Real-time RT-PCR assay was employed to detect the expression rate in 11 HCC tissues and human cancer cell lines. RESULTS: Differentially expressed 21 genes were identified, and they were classified as genes involved in protein metabolism, ubiquitin-dependent protein catabolism, carbohydrate metabolism, lipid metabolism, DNA repair, and inflammatory response. CONCLUSIONS: We identified differentially expressed genes in HCC, and these genes may play an important role in the study of hepatocarcinogenesis, development of biomarker, and target therapy for HCC.
Carcinoma, Hepatocellular/diagnosis/genetics/*metabolism ; Cell Line, Tumor ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms/diagnosis/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Tumor Markers, Biological/genetics/*metabolism ; Up-Regulation

OBJECTIVETo investigate the expressions of glypican-3 (GPC3) mRNA in hepatocellular carcinoma (HCC) tissues and peripheral blood cells (PBCs), and to determine the values of GPC3 mRNA in the diagnosis of HCC and HCC micrometastasis.

METHODSUsing semi-quantitative and nested reverse transcription polymerase chain reactions (RT-PCR), we detected the expressions of AFP and GPC3 genes in the tissues of 41 HCC, 41 paracancer and 52 non-HCC liver samples (41 far from HCC tissues and 11 normal liver tissues), and in the PBCs of 67 specimens from subjects.

RESULTSThe semi-quantitative RT-PCR displayed GPC3 mRNA was expressed in all samples of tissues and PBCs, and the relative intensities of its expressions in HCC, paracancer, non-HCC liver tissues were 78.9 +/- 35.5, 30.6 +/- 21.6, 23.8 +/- 15.5 respectively. The AFP mRNA expression values were 61.2 +/- 32.6, 31.5 +/- 23.6, and 21.2 +/- 15.9 respectively. The expression of each gene in HCC differed significantly from those in other two kinds of tissue samples (P < 0.01). The expressions of GPC3 mRNA and AFP mRNA, accounting for 80.5% and 63.4% in all the HCC tissues, were higher than their respective peak values in the tissues of non-HCC liver (+1.96s), but the expressions of at least one of the two genes was elevated in 92.7% of all the HCC tissues. There was a significant difference between combined detection of two genes and single AFP mRNA detection in HCC tissues (P < 0.01). Clinicopathologically, AFP mRNA was related with the grade of HCC and serum AFP, while GPC3 mRNA was related with not only the grade of HCC but also the invasion of HCC. The relative intensities of GPC3 mRNA expressions in PBCs of 67 specimens was 15.9 +/- 9.0, and GPC3 mRNA expressed in three kinds of tissue samples were all stronger than its counterparts in PBCs (P < 0.01). The GPC3 mRNA expression values in PBCs of the HCC group and the non-HCC group were respectively 16.1 +/- 8.3, 15.6 +/- 10.2, there was no significant difference between the two groups. Of the HCC metastasis group and the HCC non-metastasis group, the respective GPC3 mRNA expression values in PBCs were 16.0 +/- 9.0 and 16.3 +/- 7.7, there was also no significant difference between the two groups. The nested RT-PCR showed that the positive rates of AFP mRNA expressions in PBCs from the HCC group and the non-HCC group were 56.1% and 23.1%, and the difference between the two groups was significant (P = 0.011). The positive rates of AFP mRNA expressions in PBCs from the HCC metastasis group and the HCC non-metastasis group were 80.9% and 30.0%, and there was also a significant difference between the two groups (P = 0.002).

CONCLUSIONSAlthough GPC3 mRNA is expressed broadly, it still may serve as a potential tissue biomarker in the diagnosis of HCC. Detecting the expression of the two genes in the tissues will improve the screening and diagnosis of HCC. GPC3 is prevalently transcribed in the PBCs, but we have not found any relationship between the GPC3 expression in PBCs and the metastasis or recurrence of hepatocellular carcinoma, thus we can not identify HCC micrometastasis with GPC3 mRNA.

Adult ; Aged ; Carcinoma, Hepatocellular ; diagnosis ; metabolism ; pathology ; Female ; Glypicans ; biosynthesis ; genetics ; Humans ; Liver Neoplasms ; diagnosis ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; alpha-Fetoproteins ; biosynthesis ; genetics

OBJECTIVETo investigate the expression of perforin and granzyme B in rejection response following liver transplantation, and evaluate their roles to be used as predictive markers of rejection.

METHODSThe expression of perforin and granzyme B in liver biopsies obtained from liver allograft recipients was determined by immunohistochemistry. Biopsies were classified into two groups-no evidence of rejection and rejection-according to Histopathologic criteria. The relationship between the perforin/granzume B expression and acute rejection was analyzed.

RESULTSFrom 19 patients, thirty-five liver biopsies were obtained after liver transplantation. Among them, nineteen samples were diagnosed as rejection response. The frequencies of perforin and granzyme B expression in rejection group were 100% (19/19) and 94.7% (18/19), respectively. While those in no rejection group were 25.0% (4/16) and 12.5 (2/16), respectively. In most rejected samples, perforin and granzyme B were expressed simultaneously. Only three samples showed perforin expression alone, while no samples demonstrated granzyme B expression alone. There was a close relationship between perforin/granzyme B expression and liver allograft rejection.

CONCLUSIONPerforin and granzyme B expression seemed to be related to the development of acute rejection following liver transplantation, and might be served as sensitive and reliable markers in diagnosing acute rejection in early stage.

Adult ; Biomarkers ; Female ; Graft Rejection ; diagnosis ; metabolism ; Granzymes ; Humans ; Liver Cirrhosis ; surgery ; Liver Neoplasms ; surgery ; Liver Transplantation ; immunology ; Male ; Membrane Glycoproteins ; biosynthesis ; genetics ; Middle Aged ; Perforin ; Pore Forming Cytotoxic Proteins ; Serine Endopeptidases ; biosynthesis ; genetics ; T-Lymphocytes, Cytotoxic ; enzymology