Jing-An Rui

Expression of LAPTM4B-35: A novel marker of progression, invasiveness and poor prognosis of extrahepatic cholangiocarcinoma☆

LAPTM4B was proven to overexpress in hepatocellular carcinoma and relate to differentiation. We immunohistochemically investigated the expression and potential clinicopathological and prognostic significance of LAPTM4B encoded protein, LAPTM4B-35, in extrahepatic cholangiocarcinoma (EHCC) for specimens from consecutive 81 patients. LAPTM4B-35 staining was positive in cancer tissues from 59 patients (72.8%), including 12 with score 1, 22 with score 2 and 25 with score 3. No positive staining was found in non-cancer epithelia. The staining score in cancer tissues was not only significantly associated with TNM staging, histological grade, perineural and lymph node invasion (P<0.05), but also of comprehensive prognostic implications, including integrated estimation with CA19-9. These data established that LAPTM4B-35 positively expressed in a great portion of EHCC and might be a novel molecular maker of progression, invasiveness and poor prognosis.

Edmondson-Steiner Grading Increases the Predictive Efficiency of TNM Staging for Long-term Survival of Patients with Hepatocellular Carcinoma After Curative Resection

BackgroundThe 6th edition TNM staging (TNM-6) for hepatocellular carcinoma (HCC) has been recommended. However, its superiority, in contrast to the previous 5th edition (TNM-5), has not been fully recognized. Besides, tumor differentiation was not included. The current study was designed to compare the value of these two staging systems and, more importantly, to elucidate whether Edmondson-Steiner grading, a well-acknowledged histological classification, is helpful in further discriminating different prognosis of HCC.MethodsProspectively collected clinicopathological and follow-up data of consecutive 171 patients with HCC undergoing curative hepatic resection (CHR) were reviewed retrospectively. The impacts of variables on survival were determined by univariate and multivariate statistical analyses.ResultsThe differences of survival between stages of the TNM-6 and TNM-5 were almost significant, except for disease-free survival for TNM-5. Moreover, TNM-6 might be a more powerful prognostic predictor compared with TNM-5, although their impacts on survival were all not independent, unlike Edmondson-Steiner grading. For patients with each stage of TNM-6, Edmondson-Steiner grade was the sole significant variable in both univariate and multivariate analyses. Finally, a novel scoring criteria (prognostic scoring for CHR, PSCHR) integrating Edmondson-Steiner grading and TNM-6 was attempted and statistically shown to be of independent significance and stronger predicting value for prognosis of curatively resected HCC.ConclusionTNM-6 revealed to be more significantly prognostic than TNM-5 in patients with HCC after curative hepatic resection. Edmondson-Steiner grading could raise the predictive efficiency of TNM-6 for postresectional survival of patients with HCC. Therefore, PSCHR containing Edmondson-Steiner grading was preliminarily proposed.

LAPTM4B-35 is a novel prognostic factor of hepatocellular carcinoma.

LAPTM4B‐35 is a 35‐kDa tetra‐transmembrane protein overexpressed in hepatocellular carcinoma (HCC) and promotes cell survival, proliferation, and tumorigenesis. However, the potential clinical implications of LAPTM4B‐35 in HCC are still unclear. This study is aimed to investigate the correlations between LAPTM4B‐35 expression and prognosis in patients with HCC.

Outcomes and prognostic factors of cirrhotic patients with hepatocellular carcinoma after radical major hepatectomy

BackgroundRadical major hepatectomy (RMH) has been suggested as one of main options for cure of large/advanced hepatocellular carcinoma (HCC). However, its operative risk remains high and its effectiveness is still controversial, especially for patients with liver cirrhosis. The present study aims to investigate short- and long-term outcomes and to identify prognostic factors for cirrhotic patients with HCC after RMH.Materials and MethodsProspectively collected clinicopathological data of 81consecutive cirrhotic HCC patients who underwent RMH were reviewed retrospectively. The Kaplan-Meier method was adopted for evaluating long-term survival. Prognostic factors were identified by univariate and multivariate analyses.ResultsAfter RMH, perioperative mortality, overall morbidity, and life-threatening morbidity were 1.2%, 24.7%, and 12.3%, respectively. Overall and disease-free 5-year survival rates were 39.4% and 28.1%, respectively. Univariate analysis showed that presence of portal vein tumor thrombosis (PVTT) and satellite nodules, late TNM staging, high Edmondson-Steiner grading, and blood transfusion was associated with worsened prognosis. Of them, Edmondson-Steiner grading was identified as the sole independent prognostic factor for both overall and disease-free survival by multivariate analysis, whereas blood transfusion and the presence of PVTT independently predicted unfavorable overall or disease-free survival, respectively.ConclusionsThese data indicated that RMH was safe and appeared to be effective in treating cirrhotic patients with HCC. Some tumor-related and clinical variables influenced long-term outcome of these patients after RMH.

Prognostic factors of solitary large hepatocellular carcinoma: The importance of differentiation grade ☆

AIMS Solitary large hepatocellular carcinoma (SL-HCC), a novel subtype with relative good prognosis, has recently been defined. However, the concept has not been validated. Besides, prognostic factors of SL-HCC remain unknown. The present study is designed to address the issues. MATERIALS AND METHODS Clinicopathological variables and survival of consecutive 85 patients with SL-HCC after curative resection are compared with those of 48 patients with small HCC (SHCC). The prognosticators of SL-HCC are also evaluated. RESULTS Disease-free survival of SL-HCC is similar with that of SHCC, whereas significant poorer overall survival is observed in SL-HCC than that in SHCC, accompanied by more frequent vascular invasion, later TNM stage and potentially higher Edmondson-Steiner grade. Vascular invasion, Edmondson-Steiner grade, TNM stage and preoperative AFP level impact overall and/or disease-free survival of SL-HCC, but only Edmondson-Steiner grade is independent. Additionally, differences in both overall and disease-free survival between SL-HCC with Edmondson-Steiner grade I-II and SHCC are all not significant. CONCLUSIONS Factors predictive for prognosis of SL-HCC are all tumor-related. The involvement of differentiation grade might be helpful for further distinguishing a particularly good outcome in SL-HCC.

Overexpression of LAPTM4B promotes growth of gallbladder carcinoma cells in vitro

BACKGROUND The overexpression of LAPTM4B-35 in gallbladder carcinoma (GBC) and its clinicopathologic and prognostic significance have been previously shown. Thus, this gene may play a role in the growth of GBC cells. METHODS The pcDNA3-AE containing the complete open reading frame of LAPTM4B (lysosome-associated protein transmembrane-4beta) and mock (pcDNA3) plasmids were transiently transfected into GBC-SD cells. Cell proliferation, cell cycle distribution, and protein expression were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium assay, flow cytometry, and Western blot, respectively. RESULTS Cells transfected with pcDNA3-AE revealed accelerated proliferation, less serum dependence, and significant cell cycle progression compared with cells transfected with mock plasmid and parent cells. These phenotypes were accompanied by upregulated expression of C-myc, c-Fos, c-Jun, cyclin D1, and cyclin E and downregulated expression of P16 and P-27. CONCLUSIONS LAPTM4B overexpression promotes the growth of GBC cells in vitro by regulating the expression levels of some proliferation-associated proteins. Therefore, the LAPTM4B gene might be used as a novel therapeutic target of GBC.

Overexpression of LAPTM4B-35 attenuates epirubucin-induced apoptosis of gallbladder carcinoma GBC-SD cells

BACKGROUND It was shown previously that LAPTM4B promoted growth of gallbladder carcinoma (GBC) cells and predicted poor prognosis in GBC; however, its roles and relative mechanisms in apoptosis of GBC cells remain unknown. METHODS The plasmids, pcDNA3-AE, containing the complete open reading frame of LAPTM4B and Mock (pcDNA3), were transfected transiently into GBC-SD cells, followed by induction of apoptosis by epirubicin. Cell apoptosis was determined by Hoechst 33258 staining, propidium iodide (PI) staining, and Annexin V/PI double staining flow cytometry. Protein expression was detected by immunoblotting. RESULTS Overexpression of LAPTM4B-35 was observed in cells transfected with pcDNA3-AE. These cells possessed significantly less apoptosis ratios compared with cells transfected with the Mock plasmid, although the values were still greater than those in parent cells. Of the apoptosis-related molecules, expression of Bcl-2 and Bcl-xL was up-regulated in cells transfected with pcDNA3-AE, whereas expressions of Bax, Bid, and cleaved caspase-9 and -3 were down-regulated compared with their expression in other kinds of cells. CONCLUSION Our data show that LAPTM4B-35 attenuated epirubicin-induced apoptosis of GBC-SD cells in vitro through a mitochondria-dependent pathway. Therefore, the protein LAPTM4B-35 might be associated with the chemoresistance of GBC.

LCSGJ-T Classification, 6th or 5th Edition TNM Staging Did Not Independently Predict the Long-Term Prognosis of HBV-Related Hepatocellular Carcinoma After Radical Hepatectomy

BACKGROUND The 6th edition tumor-node-metastasis (TNM) staging (TNM-6) for hepatocellular carcinoma (HCC) was recommended. Besides, Liver Cancer Study Group of Japan (LCSGJ)-T classification has been recently proposed. However, these newly established staging systems should be further verified in different subgroups of HCC patients. The current study mainly aimed to validate the predictive power of these novel criteria in a cohort of patients with hepatitis B virus-related HCC after radical hepatectomy. As a control, the 5th edition TNM staging (TNM-5) was also evaluated. METHODS AND MATERIALS Clinicopathological and follow-up data of consecutive 142 patients with HBV-related HCC undergoing radical hepatectomy were reviewed. The impact of variables on prognosis was determined by uni- and multivariate analyses. RESULTS By univariate analysis, LCSGJ-T classification, TNM-6, and TNM-5 were almost significantly prognostic, except for TNM-5 for disease-free survival. Meanwhile, tumor size>or=5 cm, alpha-fetoprotein>400 ng/mL, high Edmondson-Steiner grade, presence of microvascular invasion, portal vein tumor thrombosis, satellite nodule, and resection margin<or=1 cm were also associated with decreased overall or disease-free survival. Multivariate analysis, including aforementioned factors, suggested that Edmondson-Steiner grade was the sole independent prognosticator for both overall and disease-free survival, when LCSGJ-T classification, TNM-6, and TNM-5 were entered, respectively. However, all 3 staging systems lost their predictive potentials in multivariate analysis. CONCLUSIONS LCSGJ-T classification, TNM-6, and TNM-5 were not revealed to be independently prognostic in patients with HBV-related HCC after radical hepatectomy. Therefore, these staging criteria, especially the newly developed ones, call for more support in many subsets of HCC patients.

Risk factors of poor prognosis and portal vein tumor thrombosis after curative resection of solitary hepatocellular carcinoma

BACKGROUND Predictors of poor prognosis of solitary hepatocellular carcinoma (SHCC), a subgroup encompassing most patients with the malignancy, are still controversial. Hence, risk factors for portal vein tumor thrombosis (PVTT) in SHCC are obscure. The present study was designed to address this issue. METHOD Clinicopathological and follow-up data for 156 consecutive patients with SHCC following curative hepatic resection were analyzed using uni- and multi-variate analyses. RESULTS Univariate analysis showed that PVTT, tumor-node-metastasis (TNM) stage, Edmondson-Steiner grade and preoperative serum alpha-fetoprotein (AFP) level were associated with the overall and disease-free survival, whereas tumor size only influenced the overall survival. In multivariate Cox regression tests, Edmondson-Steiner grade and TNM stage were independent prognostic markers for both overall and disease-free survival. In addition, the Chi-square test showed that AFP level and Edmondson-Steiner grade were correlated with PVTT. Among them, only Edmondson-Steiner grade was shown to be of independent significance for PVTT in multi-variate logistic regression analysis. Additionally, AFP, the sole preoperative factor for PVTT, was not adequately sensitive and specific. CONCLUSIONS Factors relating to post-surgical prognosis and PVTT in SHCC are all tumor-related. Of these, Edmondson-Steiner grade and TNM stage might be of particular importance in survival analysis. In addition, accurate prediction of PVTT by clinicopathological parameters before surgery remains difficult.

Both the 5th and 6th editions of TNM staging system fail to independently predict long-term prognosis after radical hepatectomy in hepatocellular carcinoma sized > or = 5 cm.

OBJECTIVE To validate the predictive power of the 5th and 6th editions of TNM staging system (TNM-5, TNM-6) in a Chinese patient cohort with hepatocellular carcinoma (HCC) sized > or = 5 cm after radical hepatectomy. METHODS Consecutive 121 patients with HCC sized > or = 5 cm undergoing radical hepatectomy between January 1995 and December 2002 were included. The impact of clinicopathological variables on prognosis was determined by univariate and multivariate analyses, after excluding 2 perioperative deaths. RESULTS In univariate analysis, TNM-5 stage did not show prognostic significance for overall or disease-free survival, as opposed to TNM-6 stage, Edmondson-Steiner grade, portal vein tumor thrombosis (PVTT), vascular invasion, satellite nodule, Child-Pugh grade, and hepatitis B surface antigen (HBsAg) positivity. When these significant variables were entered in multivariate analysis, Edmondson-Steiner grade was the sole independent prognosticator for both overall and disease-free survival, whereas Child-Pugh grade independently influenced disease-free survival. However, TNM-6 stage lost its predictive potential in multivariate analysis. CONCLUSIONS Neither TNM-5 nor TNM-6 staging system is revealed to be independently prognostic in patients with HCC sized > or = 5 cm after radical hepatectomy. Therefore, TNM-6 calls for more support in many subsets of HCC patients.