肝癌中骨形态发生蛋白7表达及其与生存相关性分析

目的研究肝癌组织中骨形态发生蛋白7(BMP-7)表达及其与患者预后关系。方法免疫组织化学及实时逆转录聚合酶链反应(real-time RT-PCR)方法分析肝癌组织、癌旁组织及非癌肝脏组织中BMP-7表达,选取2010年1月—2013年12月江苏省连云港市第一人民医院85例肝癌患者的癌组织及20例癌旁组织标本,以肝血管瘤及肝脏外伤患者14例为良性对照。研究BMP-7与肝癌患者临床病理特征之间关系及其不同表达患者术后生存情况。结果 BMP-7在肝癌组织、癌旁组织及非癌肝脏组织中表达的阳性率比较,差异有统计学意义(P<0.05),BMP-7的表达与患者肿瘤大小、肿瘤组织分化程度相关,其阳性表达的肝癌患者预后较阴性表达者差。结论 BMP-7与肝癌的发生、发展相关,可以作为预测患者预后情况的重要指标。

Down-regulation of FoxM1 inhibits viability and invasion of gallbladder carcinoma cells, partially dependent on inducement of cellular senescence

AIM:To investigate the effect of knockdown of forkhead box M1(foxM1)on the proliferation and invasion capacities of human gallbladder carcinoma(Gbc)-sd cells.METHODS:four foxM1 shRNAs were transfected into Gbc-sd cells with lipofectamine 2000 to select the appropriate shRNA for down-regulation of foxM1.A recombinant lentivirus for shfoxM1(lv-shfoxM1),which expresses FoxM1-specific shRNA,and a negative control carrying green fluorescent protein,which expresses a scrambled RNA,were constructed.After transfection with the recombinant adenovirus and screened with puromycin,RT-PcR and Western blot were utilized to evaluate the inhibition efficiency.cell viability was evaluated by MTT assay,and cell migration and invasion were assessed using the Transwell system.cells were suspended in serum-free medium and seeded into Transwell inserts either uncoated(for migration assay)or coated(for invasion assay)with growth factor-reduced Matrigel.To verify the involvement of foxM1 in the senescence of tumor cells,staining of senescenceβ-galactosidase(sAβ-gal),the widely used biomarker of cellular senescence,was also performed.RESULTS:After successful transfection of four foxM1small interfering RNAs(shRNAs)with lipofectamine2000,the shf1822 was selected as the most appropriate shRNA according to its obvious inhibitory effect.The recombinant adenovirus was then constructed with the shf1822 and successfully transfected into the Gbcsd cells,resulting in the significant inhibition of foxM1expression at both the mRNA and protein levels,compared with the negative control(P<0.05).After transfection,down-regulation of foxM1 significantly inhibited cell viability according to the MTT assay(P<0.05).In addition,Transwell migration and invasion assays also suggested the suppression of invasion ability of the transfected cells.sAβ-gal staining showed that downregulation of foxM1 could induce more senescent Gbc cells(P<0.05),suggesting the possible involvement of the senescence process of the foxM1-deficient cells in Gbc.CONCLUSION:foxM1 is functionally involved in viability of Gbc cells,partially dependent on the inducement of cellular senescence,and is a potential target for Gbc therapy.

透明帽辅助胆道镜在内镜保胆取石术中的应用研究

目的研究透明帽辅助胆道镜在内镜保胆取石术中的作用及意义。方法回顾性分析2018年1月-2018年9月因胆囊结石于该院住院行内镜保胆取石术的100例患者,按是否应用透明帽分为接受腹腔镜联合胆道镜手术组与腹腔镜联合透明帽辅助胆道镜治疗手术组,对比两组在胆囊探查时间、手术并发症发生率、不良反应发生率及术后3个月内结石复发情况等方面的差异。结果两组患者均完成保胆取石手术,其中腹腔镜联合透明帽辅助胆道镜组出现1例患者术后胆漏。两组均未发现因胆道镜操作引起胆囊、胆囊管出血和胆总管损伤等并发症。接受腹腔镜联合胆道镜行保胆取石术患者,平均胆囊探查时间为(27.96±12.24)min,术后出现不良反应2例,术后3个月内随访B超检查胆囊结石患者8例;接受腹腔镜联合透明帽辅助胆道镜治疗的患者,平均胆囊探查时间为(12.04±6.01)min,术后出现不良反应2例,术后3个月内随访B超检查胆囊结石患者1例。腹腔镜联合透明帽辅助胆道镜组的胆囊探查时间及术后3个月内胆囊结石患者人数均明显低于腹腔镜联合胆道镜组。两组患者手术并发症发生率和患者不良反应发生率未见明显差异。结论在腹腔镜联合胆道镜实施保胆取石术中,透明帽辅助胆道镜具有明显优势,具有一定的推广应用价值。

Highlights for α-fetoprotein in determining prognosis and treatment monitoring for hepatocellular carcinoma

AIM:To explore the prognostic value in the monitoring of treatment efficacy of serial α-fetoprotein(AFP) in hepatocellular carcinoma(HCC) patients.METHODS:We searched MEDLINE,EMBASE and COCHRANE LIBRARY through April 21,2012,to find qualifying articles.Our overall search strategy included terms for HCC,AFP,treatment response,and prognosis.Literature was limited to English-language,human studies.Studies reporting cumulative survival rates were summa-rized qualitatively.For the prognostic meta-analysis,we undertook a series of meta-analyses that summarised the Cox proportional hazard ratios(HRs) by assuming a random effects model.With regards to the correlation of AFP change with radiologic response,the categorical dichotomous variables were assessed using Poisson relative risks(RRs),which were incorporated into the random effects model meta-analysis of accuracy prediction.Between-study heterogeneity was estimated by use of the I2 statistic.Publication bias was evaluated using the Begg funnel plot and Egger plot.Sensitivity analyses were conducted first by separating systemic treatment estimates from locoregional therapy estimates,evaluating different AFP response cut-off point effects,and exploring the impact of different study sizes.RESULTS:Of 142 titles identified in our original search,11 articles(12 clinical studies) met our criteria.Six studies investigated outcome in a total of 464 cases who underwent systemic treatment,and six studies investigated outcome in a total of 510 patients who received locoregional therapy.A random-effects model metaanalysis showed that AFP response was associated with an mortality HR of 0.55(95%CI,0.47-0.65) across HCC in overall survival(OS) and 0.50(95%CI,0.38-0.65) in progression-free survival.Restricting analysis to the six eligible analyses of systemic treatment,the pooled HRs were 0.64(95%CI,0.53-0.77) for OS.Limiting analysis to the six analyses of locoregional therapy,the pooled HRs for OS was 0.39(95%CI,0.29-0.53).We showed a larger pooled HR in the 50% definition studies(HR,0.67,95%CI,0.55-0.83) compared with that from the 20% definition studies(HR,0.41,95%CI,0.32-0.53).Restricting analysis to the four studies including over 100 patients individually,the pooled HR was 0.65(95%CI,0.54-0.79),with a pooled HR for OS of 0.35(95%CI,0.23-0.46) in the studies of less than 100 patients.As to radiological imaging,43.1%(155/360) of the patients in the AFP response group presented with a radiological overall response,while the response rate decreased to 11.5%(36/313) in the patients from theAFP nonresponse group.The RR of having no overall response was significantly lower in the AFP response group than the AFP nonresponse group(RR,0.67;95%CI,0.61-0.75).In terms of disease control rate,86.9%(287/330) in the AFP response group and 51.0%(153/300) in the AFP nonresponse group showed successful disease control,respectively.The RR of disease control failure,similarly,was significantly lower in the AFP response group(RR,0.37;95%CI,0.23-0.58).But these findings could be overestimates because of publication and reporting bias.CONCLUSION:HCC patients presenting with an AFP response are at decreased risk of mortality.In addition,patients with an AFP response also present with a higher overall response rate and disease control rate.

Liver transplantation versus liver resection for hepatocellular carcinoma: a meta-analysis

BACKGROUND: Liver transplantation(LT) and liver resection(LR) are currently considered the standard treatment of patients with hepatocellular carcinoma(HCC). However, the outcomes of LT and LR are still inconclusive.DATA SOURCES: MEDLINE, EMBASE, and Cochrane Library were searched for relevant studies. Surgical safety indices such as treatment-related morbidity and mortality, and efficacy indices such as overall and tumor-free survival outcomes were evaluated. Weighted mean differences and odds ratios(ORs)were calculated using a random-effects model.RESULTS: Seventeen studies were included in this metaanalysis.LT achieved significantly higher rates of surgeryrelated morbidity(OR=1.47; 95% CI: 1.02-2.13) and mortality(OR=2.12; 95% CI: 1.11-4.05). Likewise, the 1-year survival rate was lower in LT(OR=0.86; 95% CI: 0.61-1.20). However, the 3-and 5-year survival rates were significantly higher in LT than in LR and the ORs were 1.12(95% CI: 0.96-1.30) in 3 years and1.84(95% CI: 1.49-2.28) in 5 years. Furthermore, the tumorfree survival rate in LT was significantly higher than that in LR in 1, 3, 5 years after surgery, with the ORs of 1.72(95% CI:1.24-2.41), 3.75(95% CI: 2.94-4.78) and 5.64(95% CI: 4.35-7.31),respectively.CONCLUSIONS: One-year morbidity and mortality are higher in LT than in LR for patients with HCC. However, long-term survival and tumor-free survival rates are higher in patients treated with LT than those treated with LR.

Integrated genomic analysis for prediction of survival for patients with liver cancer using The Cancer Genome Atlas

AIM To evaluate the prognostic power of different molecular data in liver cancer.METHODS Cox regression screen and least absolute shrinkage and selection operator were performed to select significant prognostic variables. Then the concordance index was calculated to evaluate the prognostic power. For the combination data, based on the clinical cox model, molecular features that better fit the model were combined to calculate the concordance index. Prognostic models were built based on the arithmetic summation of the significant variables. Kaplan-Meier survival curve and log-rank test were performed to compare the survival difference. Then a heatmap was constructed and gene set enrichment analysis was performed for pathway analysis.RESULTS The m RNA data were the most informative prognostic variables in all kinds of omics data in liver cancer, with the highest concordance index(C-index) of 0.61. For the copy number variation, methylation and mi RNA data, the combination of molecular data with clinical data could significantly boost the prediction accuracy of the molecular data alone(P < 0.05). On the other hand, the combination of clinical data with methylation, mi RNA and m RNA data could significantly boost the prediction accuracy of the clinical data itself(P < 0.05). Based on the significant prognostic variables, different prognostic models were built. In addition, the heatmap analysis, survival analysis, and gene set enrichment analysis validated the practicability of the prognostic models.CONCLUSION In all kinds of omics data in liver cancer, the m RNA data might be the most informative prognostic variable. The combination of clinical data with molecular data might be the future direction for cancer prognosis and prediction.

Correction to“Downregulation of FoxM1 inhibits the viability and invasion of gallbladder carcinoma cells,partially dependent on the induction of cellular senescence”

We corrected the mistake of Figure 3,and replaced the incorrect images with the correct ones.The“adenovirus”was a typographical error in writing,and should be revised to“lentivirus”.