ObjectiveTo systematically review the expression of E-cadherin protein and the risk of pancreatic cancer. MethodsWe searched PubMed, EMbase, The Cochrane Library, CNKI, VIP, CBM and WanFang Data from inception to October 2016 to collect case-control studies about the correlation between E-cadherin protein expression and the risk of pancreatic cancer. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.2 software and Stata 12.0 software. ResultsSeventeen studies (986 cases in pancreatic cancer group and 433 cases in normal pancreatic tissue group) were finally included. The results of meta-analysis showed that: the expression of E-cadherin protein in the pancreatic cancer group was lower than normal tissue group (OR=0.04, 95%CI 0.01 to 0.23, P=0.000 2), poor differentiation group was lower than high or middle differentiation group (OR=0.44, 95%CI 0.26 to 0.76, P=0.003), lymph node metastasis group was lower than without lymph node metastasis group (OR=0.50, 95% CI 0.31 to 0.81, P=0.005), and the difference was statistically significant. However, there was no significant difference between the clinical stageⅠ-Ⅱ group and Ⅲ-Ⅳ group (OR=0.63, 95%CI 0.25 to 1.59, P=0.33), pancreatic head cancer group and pancreatic body and tail cancer group (OR=1.22, 95%CI 0.72 to 2.07, P=0.46), pancreatic cancer with nerve invasion group and without nerve invasion group (OR=1.45, 95%CI 0.81 to 2.62, P=0.21), pancreatic cancer with vascular invasion group and without vascular invasion group (OR=0.55, 95%CI 0.13 to 2.22, P=0.40). ConclusionLower expression of E-cadherin protein is significantly associated with the risk of pancreatic cancer. Due to the limited quality and quanity of includied studies, the above conclusion should be approved by more studies.
ObjectiveTo systematically review the prognostic value of E-cadherin expression in stage I non-small cell lung cancer (NSCLC).
MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 1, 2015), CNKI, CBM and WanFang Data were searched to collect cohort studies about the prognostic value of E-cadherin expression in stage I NSCLC from inception to Jun. 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software.
ResultsA total of 9 cohort studies, involving 1028 patients were included. The results of meta-analysis showed that, the lower E-cadherin expression group had a lower overall survival rate than that of the higher E-cadherin expression group (HR=1.74, 95%CI 1.36 to 2.24, P＜0.00001). However, there was no significant difference between two groups in disease free survival (HR=2.08, 95%CI 0.8 to 5.40, P=0.13). Subgroup analysis showed that, the lower E-cadherin expression group had a worse overall survival when groups were divided by different cut-off values, E-cadherin location site or different nations (all value P＜0.05).
ConclusionCurrent evidence shows that, reduced E-cadherin expression could predict poor prognostic outcome in patients with stage I NSCLC. Due to the limited quantity and quality of included studies, the above conclusions need to be verified by more high quality studies.
ObjectiveTo explore the relationship between aberrant promoter CpG islands methylation status of E-cadherin gene and hepatocarcinogenesis, and to assess its significance in clinical early diagnosis of hepatocellular carcinoma (HCC). MethodsSurgically resected specimens, among which cancerous and corresponding noncancerous liver tissues from 34 HCC patients, 10 liver cirrhosis from patients without HCC and normal liver tissues from 4 accidental deaths, were collected in West China Hospital. Breast cancer cell line MDA-MB-435 with promoter CpG islands hypermethylation of E-cadherin as positive control was gained from the Cell Bank of Chinese Academy of Sciences in Shanghai. The methylation status of promoter CpG island of E-cadherin gene was detected by nested methylationspecific polymerase chain reaction (nested-MSP). ResultsE-cadherin gene promoter CpG islands hypermethylation was found in 61.76% (21/34) of cancerous tissues, in 29.41% (10/34) of noncancereous tissues from the 34 HCC patients and in 50.00% (5/10) liver cirrhosis from patients without HCC. None of the 4 normal liver samples were detected E-cadherin mehylation positive. Moreover, the methylation of E-cadherin gene was significantly more frequent in 34 cancerous than that in corresponding noncancerous liver tissues (Plt;0.05), which had no significant difference between the 10 cirrhotic samples and cancerous or non-cancerous liver tissues (Pgt;0.05). In 34 cancerous samples, with the combination of both biomarkers of E-cadherin methylation and AFP400 (serum AFP level at a cutoff of 400 μg/L), the diagnostic sensitivity of HCC increased to 82.35%. ConclusionsThe aberrant promoter methylation of E-cadherin gene may play a vital role in the development and progression of HCC. Moreover, it might be an early event in hepatocarcinogensis. It is of high value to make further study to confirm the significance of E-cadherin gene methylation in clinical diagnosis and therapy.
ObjectiveTo systematically review the correlation between E-cadherin expression and prostate cancer, as well as its clinicopathologic features in Chinese population.
MethodsSuch databases as PubMed, EMbase, CBM, CNKI, VIP and WanFang Data were electronically searched from their inception to December, 2015 to collect case-control studies about the correlation between E-cadherin expression and prostate cancer, as well as its clinically pathologic features in Chinese population. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software.
ResultsA total of 21 studies were included, involving 920 prostate cancer cases, 415 benign prostatic hyperplasia cases, and 48 controls. The results of meta-analysis showed that the prostate cancer group had a lower E-cadherin expression level when compared with the benign prostatic hyperplasia group (OR=0.07, 95%CI 0.05 to 0.11, P<0.00001) or the control group (OR=0.04, 95%CI 0.01 to 0.18, P<0.00001). Moreover, the expression level of E-cadherin was lower in the low and medium differentiation group than in the high differentiation group (OR=0.13, 95%CI 0.08 to 0.23, P<0.00001), lower in the stage of C+D than in the stage of A+B (OR=0.23, 95%CI 0.15 to 0.34, P<0.00001), and lower in the prostate cancer with metastasis (OR=0.46, 95%CI 0.27 to 0.79, P=0.005) and it was decreased gradually with the increment of pathological differentiation and clinical stage of prostate cancer and with the decrement of lymph node or bone metastasis and serum PSA level.
ConclusionCurrent evidence indicates that the expression level of E-cadherin is significantly correlated with prostate cancer and its clinicopathologic features in Chinese population. Due to limited sample size and quality of included studies, the conclusion needs to be verified by conducting more high quality studies.
ObjectiveTo explore the effect of small interference RNA (siRNA) on the metastasis and invasion of A549 cells after silence the E-cadherin gene (CDH1).MethodsThe CDH1 gene in A549 cells was silenced by siRNA technology, and RT-QPCR and Western blot were used to detect the gene expression and protein expression after silencing. The cells were divided into control group (Control), siRNA negative group (siRNA-NC) and siRNA gene silencing group (siRNA-CDH1). CCK-8 detected cell viability after the gene silencing in 12 h, 24 h, 48 h and 72 h, and cell scratch test to detect cell migration ability. Transwell chamber was used to detect cell invasiveness, and Western blot method was used to detect the expression level of key factors which involved in cell migration, invasion, such as vimentin, matrix metalloproteinases (MMP-2 and MMP-9), and N-cadherin. RT-QPCR was employed to detect the mRNA expression of vimentin, MMP-2, MMP-9, Slug and Snail.ResultsAfter CDH1 silencing, the activity of A549 cells increased significantly and was time-dependent, compared with Control group and siRNA-NC group (P<0.05). The cell scratch test and Transwell chamber test showed that the cell migration and invasion ability increased significantly after CDH1 silencing, compared with Control group and siRNA-NC group (P<0.05). The expression of vimentin, MMP-9, MMP-2 and N-cadherin in siRNA-CDH1 group increased significantly. The mRNA expression level of vimentin, MMP-9, MMP-2 and Slug and Snail also increased. Compared with Control group and siRNA-NC group, the difference was statistically significant (P<0.05).ConclusionCDH1 plays an important role in tumor proliferation and invasion, and its deletion can increase the proliferation and invasion ability of A549 cells.
【Abstract】ObjectiveTo study the effect of down-regulation of E-cadherin on the invasion ability of tumor cells. MethodsHuman pancreatic carcinoma cell line JHP-1 was treated with E-cadherin antisense oligodeoxynucleotied (ASODN). The immunocytochemistry, Western blot were used to detect the expression and the contents of E-cadherin in the tumor cells, and the invasive ability of tumor cells were evaluated by invasive-MTT assay. Results Treated with E-cadherin ASODN, the expression of E-cadherin on JHP-1 cells were reduced, and the protein contents were decreased as well compared with control groups and ODN group. The invasive ability of JHP-1 cells to the basement membrane was increased (P＜0.001) compared with ODN group and control group. ConclusionE-cadherin was related to the invasive ability of tumor cells.
Objective To explore the expressions of E-cadherin， matrix metalloproteinases-2 （MMP-2） protein，and matrix metalloproteinases-9 （MMP-9） protein in gastric cancer tissues， and to analyze the possible statistical relati-onship between the expressions of E-cadherin， MMP-2 protein， and MMP-9 protein， and clinicopathological features ofgastric cancer. Methods The ABC immunohistochemical staining was adopted to examine the expressions of E-cadherin，MMP-2 protein， and MMP-9 protein in 40 paraffin slices of gastric cancer （gastric cancer group）， with the adjacent tissue as the control group （adjacent tissue group）. The positive rates of 3 kinds of protein were compared between the2 groups， in addition， the statistical relationship between the expressions of the 3 kinds of protein and clinicopathological features of gastric cancer was examined respectively by SPSS 19.0 software. Results The expressions of E-cadherin， MMP-2 protein， and MMP-9 protein were all found in gastric cancer tissues and adjacent tissues. In gastric cancer tissue group， the expression of E-cadherin downregulated while the expressions of MMP-2 protein and MMP-9 protein upregulated in comparison to adjacent tissue group （P＜0.05）. The significant association was found between the expre-ssion of E-cadherin and the gastric cancer tissues of T3＋T4 stage， N1-N3 stage， and Ⅲ＋Ⅳ stage， which had lower positive expression rate （P＜0.05）. The expression of MMP-2 protein in gastric cancer tissues of M1 stage and Ⅲ＋Ⅳstage upregulated （P＜0.05）， and the expression of MMP-9 protein upregulated in gastric cancer tissues of T3＋T4 stage，Ⅲ＋Ⅳ stage， or lowlydifferentiated＋undifferentiated （P＜0.05）. No significant relationship was found in other clinical-pathological features and 3 kinds of protein except aforementioned significant relationship （P＞0.05）. Conclusions In the development progress of gastric cancer， the E-cadherin may get involved in the mechanism of tumor invasion and lymph node metastasis， MMP-2 protein may get involved in the mechanism of distant metastasis， and MMP-9 protein may get involved in the mechanism of differentiation and tumor invasion. The examination of those 3 kinds of markers may play an role in the judgment of tumor stage and estimation of prognosis in gastric cancer clinically.
ObjectiveTo determine the level of CDH1 gene promoter hypermethylation in human gastric carcinoma by establishing MS-PCR method, and analyze retrospectively the possible statistical relationship between CDH1 gene promoter hypermethylation in human gastric carcinoma and HP infection, tumor differentiation, invasion, lymph nodal and distant metastasis, respectively.
MethodsThe bisulfite conversion MS-PCR method was adopted to examine the level of CDH1 gene promoter hypermethylation in 40 cases of human gastric carcinoma tissue collected between January 2008 and December 2009. The statistical relationship between CDH1 gene promoter hypermethylation in human gastric carcinoma and HP infection, tumor differentiation, invasion, lymph nodal and distant metastasis were examined respectively with SPSS statistical tools.
ResultsThe positive rate of CDH1 gene promoter hypermethylation in gastric carcinomas (67.5%) was higher than that in paired normal gastric mucosae (12.5%), and the difference was significant (P<0.05). In gastric carcinomas, the positive rate of CDH1 gene promoter hypermethylation in well differentiated or moderately differentiated groups (22.2%) was lower than that in poorly differentiated groups (80.6%), and the difference was significant (P<0.05). The positive rate of CDH1 gene promoter hypermethylation in HP positive groups (78.1%) was higher than that in HP negative groups (25.0%), and the difference was significant (P<0.05).
ConclusionCDH1 gene promoter hypermethylation may play an important role in the process of tumor carcinogenesis in gastric carcinomas. Meanwhile, the CDH1 gene promoter hypermethylation may lead to poor differentiation in gastric carcinomas. CDH1 gene promoter hypermethylation is related to HP infection in the original gastric carcinomas, which shows that HP may get involved in the process of tumor suppressor gene methylation/inactivation and tumor development process.
ObjectiveTo summarize the role of epithelial-mesenchymal-transition （EMT） in occurrence and development of gastrointestinal cancer. MethodsDomestic and international publications online involving EMT of gastrointestinal cancer in recent years were collected and reviewed. ResultsEMT was a highly conserved process that has been well characterised in embryogenesis. Studies had shown that the aberrant activation of EMT in adult epithelia could promote tumour metastasis by repressing cell adhesion molecules. E-cadherin， one of the epithelial cell markers, maybe involved in the process of the EMT, especially of the Ecadherin transcriptional repressors， these transcriptional repressors significantly increased in the gastrointestinal cancer. Further more， EMT might involve in the process of gastrointestinal cancer stem cells formation. ConclusionsEMT and it’s regulators play a very important role in gastrointestinal cancer， and may provide a newsight into the gastrointestinal cancer. It also can provide a novel clinical targets to treat the gastrointestinal cancer.
