Expression of monocyte chemotactic protein-1/CCL2 in gastric cancer and its relationship with tumor hypoxia

AIM:To investigate the expression and prognostic value of CCL2 in gastric cancer,as well as its relationshipwith tumor hypoxia.METHODS:Tumor tissues from 68 gastric cancer patients(GC)were analyzed,and the expression of CCL2and hypoxia-inducible factor 1 alpha(HIF-1α)in tumortissues was detected by immunohistochemistry.Statistical evaluations that were used included univariate logrank tests of Kaplan-Meier curves and multivariate Coxregression model analysis.RESULTS:CCL2 was highly expressed in 66.2%(45/68)of gastric cancer specimens.The distribution of CCL2expression in tumor tissue was consistent with thatof HIF-1α.Patients with high CCL2 expression in GChad a lower overall survival rate[50.6 mo(95%CI:44.44-56.93)vs 64.6 mo(95%CI:60.27-68.94),P=0.013].CONCLUSION:CCL2 expression correlates closely with HIF-1αexpression in gastric cancer.CCL2 may be an independent prognostic marker for GC.     

Association between cadherin-17 expression and pathological characteristics of gastric cancer:A meta-analysis

AIM: To construct a meta-analysis in order to examine the relationship between cadherin-17(CDH17) andgastric cancer(GC). METHODS: Related articles were selected by searching the following English or Chinese electronic databases: CINAHL, MEDLINE, Science Citation Index, the Chinese Journal Full-Text, and the Weipu Journal. NewcastleOttawa Scale(NOS) criteria were used to ensure consistency in reviewing and reporting results. Statistical analyses were conducted with Version 12.0 STATA statistical software.RESULTS: Ultimately, 11 articles, with a total of 2,120 GC patients, were found to be eligible for study inclusion. In comparisons of GC patients by TNM stage(Ⅲ-Ⅳ vs ?Ⅰ-Ⅱ: OR = 2.35, 95%CI: 1.15-4.825, P = 0.019), histologic grade(3-4 vs 1-2: OR = 3.48, 95%CI: 1.36-8.92, P = 0.009), invasion grade(T3-4 vs T1-2: OR = 2.86; 95%CI: 1.69-4.83; P = 0.000), and lymph node metastasis(positive vs negative: OR = 2.64; 95%CI: 1.33-5.27; P = 0.006), it was found that CDH17 showed more positive expressions in each of the more severe cases. Country-stratified analyses from all four experimental subgroups showed that high CDH17 expression levels may be related to GC among Chinese and Korean populations(all P < 0.05), with the exception of the invasion grade T3-4 vs T1-2 comparison, where the relation only held among the Chinese population(OR = 2.86, 95%CI: 1.69-4.83, P = 0.000). CONCLUSION: Collectively, the data reflects the capacity of CDH17 in tumor proliferation and metastasis among GC patients.     

Helicobacter pylori infection and esophageal cancer risk:An updated meta-analysis

AIM:To clarify the association between Helicobacter pylori(H.pylori)infection and the risk of esophageal carcinoma through a meta-analysis of published data.METHODS:Studies which reported the association between H.pylori infection and esophageal cancer published up to June 2013 were included.The odds ratios(ORs)and corresponding 95%CIs of H.pyloriinfection on esophageal cancer with respect to health control groups were evaluated.Data were extracted independently by two investigators and discrepancies were resolved by discussion with a third investigator.The statistical software,STATA(version 12.0),was applied to investigate heterogeneity among individual studies and to summarize the studies.A meta-analysis was performed using a fixed-effect or random-effect method,depending on the absence or presence of significant heterogeneity.RESULTS:No significant association between H.pylori infection and esophageal squamous cell carcinoma(ESCC)risk was found in the pooled overall population(OR=0.97,95%CI:0.76-1.24).However,significant associations between H.pylori infection and ESCC risk were found in Eastern subjects(OR=0.66,95%CI:0.43-0.89).Similarly,cytotoxin-associated gene-A(CagA)positive strains of infection may decrease the risk of ESCC in Eastern subjects(OR=0.77,95%CI:0.65-0.92),however,these associations were not statistically significant in Western subjects(OR=1.26,95%CI:0.97-1.63).For esophageal adenocarcinoma(EAC)the summary OR for H.pylori infection and CagA positive strains of infection were 0.59(95%CI:0.51-0.68)and 0.56(95%CI:0.45-0.70),respectively.CONCLUSION:H.pylori infection is associated with a decreased risk of ESCC in Eastern populations and a decreased risk of EAC in the overall population.     

Expression of HSP90 and HIF-1α in human colorectal cancer tissue and its significance

Objective:To investigate the expression of HSP90 and HIF-1αin human colorectal cancer tissue,the influence of HSP90 and HIF-1αon human colorectal cancer biological behavior and their related factors.Methods:The expression of HSP90 and HIF-1 a protein in human colorectal cancer as well as normal tissue were detected by imnmnohistochemical method.Results:The positive expression rates of HSP90 and HIF-1αprotein in normal human colorectal tissue as well as colorectal cancer tissue were 30%vs.63.0%,15.0%vs.71.7%,respectively.There were significant difference(P=0.035 and P=0.005 respectively).The expression of HSP90 was significantly correlated with the differentiation,Dukes stages and lymph node metastasis(P0.05),while the expression of HIF-1 a was significantly correlated with the Dukes stages and lymph node metastasis(P0.05).Association analysis showed that the expression of HSF90 protein was significantly correlated with that of HIF-1αprotein(P0.01).Conclusions:The expression of HSP90 and HIF—1αprotein may be related to the development,metastasis and invasion of human colorectal cancer,and their synergistic effects may participate in the development of the colorectal carcinoma.     

Expression and clinical significance of CD73 and hypoxia-inducible factor-1α in gastric carcinoma

AIM: To investigate the expression of CD73 and hypoxia-inducible factor-1α (HIF-1α) in human gastric carcinoma, and explore their clinical significance and prognostic value. METHODS: CD73 and HIF-1α expressions were detected by immunohistochemistry in consecutive sections of tissue samples from 68 gastric carcinoma patients. The peritumor tissues 2 cm away from the tumor were obtained and served as controls. The presence of CD73 and HIF-1α was analyzed by immunohis-tochemistry using the Envision technique. RESULTS: CD73 and HIF-1α expressions in gastric carcinoma were significantly higher than those in gastric mucosal tissues as control (P < 0.001) and showed a close correlation (Spearman r = 0.390, P = 0.001). Overexpression of CD73 was positively correlated with differentiation of tumor (P = 0.000), histopathology (P = 0.041), depth of invasion (P < 0.001), nodal status (P = 0.003), metastasis (P = 0.013), and the American Joint Committee on Cancer (AJCC) stage (P < 0.001). High expression of HIF-1α was positively correlated with tumor diameter (P = 0.031), depth of invasion (P = 0.022), and AJCC stage (P = 0.035). The overall survival rate was low in the patients with high expression of CD73 (P < 0.001). Moreover, CD73+/HIF-1α+ patients had the worst prognosis (P < 0.001). CD73 expression was proven to be an independent predictor for patients with gastric carcinoma by both multivariate Cox regression analysis (P = 0.021) and receiver operating characteristic curves (P = 0.001).CONCLUSION: CD73 expression correlates closely with HIF-1α expression in gastric carcinoma. CD73 could be an independent prognostic indicator for gastric carcinoma.     

Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

AIM:To investigate the expression of PTEN/MMAC_1/TEP_1and vascular endothelial growth factor(VEGF),their rolesin biologic behavior and angiogenesis and their associationin gastric cancer.METHODS:Immunohistochemical staining was used toevaluate the expression of PTEN,VEGF and microvasculardensity(MVD)on paraffin-embedded sections in 70 patientswith primary gastric cancer and 24 patients with chronicsuperficial gastritis(CSG).Expression of PTEN,VEGF andMVD were compared with clinicopathological features ofgastric cancer.The relationship between expression ofPTEN,VEGF and MVD as well as the relationship betweenPTEN and VEGF expression in caner cells were investigated.RESULTS:PTEN expression significantly decreased(t=3.98,P<0.01)whereas both VEGF expression and MVD significantincreased(t=4.29 and 4.41,respectively,both P<0.01)in gastric cancer group compared with CSG group.PTENexpression was significantly down-regulated(t=1.95,P<0.05)whereas VEGF expression(t=2.37,P<0.05)andMVD(t=3.28,P<0.01)was significantly up-regulated inadvanced gastric cancer compared with early-stage gastriccancer.PTEN expression in gastric cancer showed a negativeassociation with lymph node metastasis(t=3.91,P<0.01),invasion depth(t=1.95,P<0.05)and age(t=4.69,P<0.01).MVD in PTEN-negative gastric cancer was significantlyhigher than that in PTEN-positive gastric cancer(t=3.69,P<0.01),and there was a negative correlation betweenPTEN expression and MVD(γ=-0.363,P<0.05).VEGFexpression was positively associated with invasion depth(especially with serosa invasion,t=4.69,P<0.01),lymphnode metastasis(t=2.31,P<0.05)and TNM stage(t=3.04,P<0.01).MVD in VEGF-positlve gastric cancer was significantlyhigher than that in VEGF-negative gastric cancer(t=4.62,P<0.01),and there was a positive correlation betweenVEGF expression of and MVD(γ=0.512,P<0.05).VEGFexpression in PTEN-negative gastric cancer was significantlystronger than that in PTEN-positive gastric cancer(t=2.61,P<0.05),and there was a significantly negative correlationbetween the expression of VEGF and PTEN(γ=-0.403,P<0.O5). CONCLUSION:Our results imply that inactivation of PTENgene and over-expression of VEGF contribute to theneovascularization and progression of gastric cancer.PTEN-related angiogenesis might be attributed to its up-regulationof VEGF expression.PTEN and VEGF could be used as themarkers reflecting the biologic behaviors of tumor and viabletargets in therapeutic approaches to inhibit angiogenesis ofgastric cancers.Zhou YJ,Xiong YX,Wu XT,Shi D,Fan W,Zhou T,Li YC,Huang X.Inactivation of PTEN is associated with increasedangiogenesis and VEGF overexpression in gastric cancer.WorldJ Gastroenterol 2004;10(21):3225-3229http://www.wjgnet.com/1007-9327/10/3225.asp     

Diabetes mellitus carries a risk of gastric cancer:A metaanalysis

AIM:To investigate the association and quantify the relationship between diabetes mellitus(DM) and gastric cancer(GC) by an updated meta-analysis.METHODS:The initial PubMed search identified 1233publications. Studies not reporting GC or those not reporting actual number of GC were excluded. Twelve pertinent studies were retrieved from the PubMed database or from a manual search and considered for the meta-analysis. Pooled risk ratios and 95%CI were estimated by a random-effects model. Subgroup analysis was performed according to gender or geographical regions. Heterogeneity and publication bias were evaluated by I2and funnel plot analysis,respectively.RESULTS:DM was significantly associated with GC with a RR of 1.41(P = 0.006)(95%CI:1.10-1.81).Subgroup analyses revealed that both sexes showed a significant association with GC,with a greater magnitude of risk in females(RR = 1.90; 95%CI:1.27-2.85;P = 0.002) than in males(RR = 1.24; 95%CI:1.08-1.43;P = 0.002). In addition,the link between DM and GC was significant in East Asian DM patients(RR = 1.77;95%CI:1.38-2.26; P < 0.00001) but not in Western DM patients(RR = 1.23; 95%CI:0.90-1.68; P = 0.2).There was no evidence of publication bias,but the results indicated significant heterogeneity.CONCLUSION:This updated meta-analysis has provided evidence of positive DM-GC associations. The limited information on potentially important clinical confounding factors in each study deserves further investigation.     

HIF-1α-1790G>A polymorphism significantly increases the risk of digestive tract cancer:A meta-analysis

AIM:To investigate the association between hypoxiainducible factor-1α(HIF-1α) polymorphisms(-1772CT and-1790GA) and the risk of digestive tract cancer.METHODS:A total of 13 eligible studies were retrieved from Pub Med,EMBASE,and the ChinaNational Knowledge Infrastructure database.The odds ratios(ORs) and 95% confidence intervals(CIs) were calculated to estimate the strength of the associations.RESULTS:By pooling the eligible studies,we found that the HIF-1α-1772CT polymorphism was not associated with the risk of developing digestive tract cancer(dominant comparison,OR:1.156; 95%CI:0.839-1.593; P heterogeneity = 0.007),and no significant association was found in the Asian population or the Caucasian population.However,for the-1790GA polymorphism,carriers of the variant-1790 A allele had a significantly increased risk of digestive tract cancer compared with those with the wildtype-1790 G allele(dominant comparison,OR:3.252; 95%CI:1.661-6.368; P heterogeneity 0.001).Additionally,this increased risk of digestive cancer was only detected in Asians; there was no significant association in Caucasians.CONCLUSION:This meta-analysis demonstrates that the HIF-1α-1790GA polymorphism is associated with a significantly increased risk of digestive tract cancer,while the-1772CT polymorphism is not.     

Abnormal β-catenin immunohistochemical expression as a prognostic factor in gastric cancer: A meta-analysis

AIM: To evaluate the effect of β-catenin immunohistochemical expression on the prognosis of gastric cancer (GC).METHODS: We searched Pubmed and Embase to identify eligible studies. The search ended on November 10, 2013, with no lower date limit. The citation lists associated with the studies were used to identify additional eligible studies. We included studies reporting sufficient information to estimate the HR and 95%CI, and information to estimate the OR in the analysis of clinicopathological features. The qualities of these studies were assessed using the Newcastle-Ottawa Quality Assessment Scale. HRs and ORs and their variance were calculated and pooled using Review Manager Version 5.2.RESULTS: A total of 24 studies were identified and comprised 3404 cases. β-catenin expression was significantly correlated with poor overall survival (OS) in GC patients (HR = 1.85, 95%CI: 1.39-2.46), but showed a significant degree of heterogeneity (I² = 71%, P < 0.0001). Subgroup analysis indicated that an abnormal pattern of β-catenin expression had an unfavorable effect on OS (HR = 1.79, 95%CI: 1.39-2.32). However, accumulation in the nucleus or loss of membrane did not influence the survival of GC patients independently. Moreover, the combined OR of β-catenin indicated that β-catenin expression was associated with Lauren classification (OR = 1.98, 95%CI: 1.19-3.29), lymph node metastasis (OR = 2.00, 95%CI: 1.44-2.77), distant metastasis (OR = 2.69, 95%CI: 1.35-5.38) and grade of differentiation (OR = 2.68, 95%CI: 1.66-4.34). β-catenin expression did not correlate with TNM stage (OR = 1.34 95%CI: 0.96-1.86), the depth of invasion (OR = 1.48, 95%CI: 0.94-2.33) or vascular invasion (OR = 1.11, 95%CI: 0.70-1.76).CONCLUSION: Abnormal β-catenin immunohistochemical expression may be associated with tumor progression and could be a predictive factor of poor prognosis in patients with GC.     

Risk factors for lymph node metastasis in T1 esophageal squamous cell carcinoma: A systematic review and meta-analysis

BACKGROUND Lymph node metastasis(LNM)affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma(ESCC).However,reports of the risk factors for LNM have been controversial.AIM To evaluate risk factors for LNM in T1 ESCC.METHODS We searched Embase,PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC.Included studies were divided into LNM and non-LNM groups.We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features.Odds ratio(OR),mean differences and 95%confidence interval(CI)were assessed using a fixed-effects or randomeffects model.RESULTS Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria.After excluding studies with heterogeneity based on influence analysis,tumor size(OR=1.93,95%CI=1.49-2.50,P<0.001),tumor location(OR=1.46,95%CI=1.17-1.82,P<0.001),macroscopic type(OR=3.17,95%CI=2.33-4.31,P<0.001),T1 substage(OR=6.28,95%CI=4.93-8.00,P<0.001),differentiation(OR=2.11,95%CI=1.64-2.72,P<0.001)and lymphovascular invasion(OR=5.86,95%CI=4.60-7.48,P<0.001)were found to be significantly associated with LNM.Conversely,sex,age and infiltrative growth pattern were not identified as risk factors for LNM.CONCLUSION A tumor size>2 cm,lower location,nonflat macroscopic type,T1b stage,poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.     

3D conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

AIM:To compare transcatheter arterial chemoembolization(TACE)and 3D conformal radiotherapy(3D-CRT)with TACE monotherapy in hepatocellular carcinoma(HCC).METHODS:We searched all the eligible studies from the Cochrane Library,Pub Med,Medline,Embase,and CNKI.The meta-analysis was performed to assess the survival benefit,tumor response,and the decline inα-fetoprotein(AFP)level.According to the heterogeneity of the studies,pooled OR with 95%CI were calculated using the fixed-effects or random-effects model.An observed OR>1 indicated that the addition of 3D-CRT to TACE offered survival benefits to patients that could be considered statistically significant.Statistical analyses were performed using Review Manager Software.RESULTS:Ten studies met the criteria to perform a meta-analysis including 908 HCC participants,with 400patients in the TACE/3D-CRT combination group and508 in the TACE alone group.TACE combined with 3DCRT significantly improved 1-,2-and 3-year overall survival compared with TACE monotherapy(OR=1.87,95%CI:1.37-2.55,P<0.0001),(OR=2.38,95%CI:1.78-3.17,P<0.00001)and(OR=2.97,95%CI:2.10-4.21,P<0.00001).In addition,TACE plus 3DCRT was associated with a higher tumor response(complete remission and partial remission)(OR=3.81;95%CI:2.70-5.37;P<0.00001),and decline rates of AFP level(OR=3.24,95%CI:2.09-5.02,P<0.00001).CONCLUSION:This meta-analysis demonstrated that TACE combined with 3D-CRT was better than TACE monotherapy for patients with HCC,which needs to be confirmed by large multicenter trials.     

TNF-a-308 polymorphism and risk of digestive system cancers:A meta-analysis

AIM:To evaluate the association between the tumour necrosis factor alpha-308(TNF-a-308)gene polymorphism and the risk of digestive system cancers.METHODS:All eligible case-control studies published up to December 2012 were identified by searching PubMed,Web of Science,Embase and China National Knowledge Internet without language restrictions.The risk of digestive system cancers associated with the TNF-a-308 polymorphism was estimated for each study using odds ratio(OR)together with its 95%CI,respectively.Cochrane Collaboration RevMan 5.1 was used to perform the analysis.Aχ2-test-based Q statistic test and an I2test were performed to assess the betweenstudy heterogeneity.When the Q test was significant(P<0.05)or I2>50%,the random effects model was used,otherwise the fixed effects model was used.RESULTS:Fifty-eight studies from fifty-five publications with a total of 9986 cancer patients and 15511 healthy controls were included.Overall,a significant association was found between the TNF-a-308 polymorphism and the risk of digestive system cancers[dominant model:OR=1.23,95%CI:1.09-1.39,(G/A)vs(G/G):OR=1.15,95%CI:1.02-1.28,(A/A)vs(G/G):OR=1.44,95%CI:1.19-1.73,recessive model:OR=1.38,95%CI:1.15-1.66].Furthermore,when the analysis was stratified by ethnicity,similar results were observed in both the Asian and Caucasian populations,except for the dominant model and heterozygote comparisons in the Asian population[dominant model:OR=1.24,95%CI:0.99-1.56,(G/A)vs(G/G):OR=1.09,95%CI:0.96-1.24].When the cancer type subgroups were examined,similar results were detected in gastric and hepatocellular carcinomas;however,no significant association was observed among other digestive system cancers.CONCLUSION:The TNF-a-308 gene polymorphism may be significantly associated with the risk of gastric and hepatocellular carcinomas,but not colorectal,pancreatic,or oesophageal cancer,in the Asian population.     

Conventional transarterial chemoembolization vs microsphere embolization in hepatocellular carcinoma: A meta-analysis

AIM:To compare conventional transarterial chemoembolization(c-TACE)with microsphere embolization in hepatocellular carcinoma(HCC).METHODS:We searched Pub Med,Medline,Embase and the Cochrane Library for trials assessing the efficacy and safety of c-TACE in comparison with those of yttrium-90 microsphere or drug-eluting bead embolization from January 2004 to December 2013.Overall survival rate(OSR),tumor response[complete response,partial response(PR),stable disease(SD),progressive disease(PD)],α-fetoprotein(AFP)response,progression rate and complications were compared and analyzed.Pooled ORs with 95%CI were calculated using either the fixed-effects model or random-effects model.All statistical analyses were conducted using the Review Manager(version 5.1.)from the Cochrane collaboration.RESULTS:Thirteen trials were identified,including a total of 1834 patients;1233 were treated with c-TACE,377 underwent yttrium-90 microsphere embolization and 224 underwent drug-eluting bead embolization.The meta-analysis with either the random-effects model or fixed-effects model indicated that microsphere embolization was associated with significantly higher OSRs compared with those of c-TACE(OR1-year=1.38,95%CI1-year:1.05-1.82;OR2-year=2.88,95%CI2-year:1.18-7.05;OR3-year=2.15,95%CI3-year:1.18-3.91).The complete tumor response rates of patients who underwent microspheres embolization were significantly higher than those of patients treated with c-TACE(OR=2.19,95%CI:1.31-3.64).The tumor progression rate after microsphere embolization was markedly lower than that after c-TACE(OR=0.56,95%CI:0.39-0.81).There was no significant difference between microsphere embolization and c-TACE in PR(OR=0.73,95%CI:0.47-1.15),SD(OR=1.07,95%CI:0.79-1.44),PD(OR=0.75,95%CI:0.33-1.68),AFP response(OR=1.38,95%CI:0.64-2.94)and complications(OR=0.68,95%CI:0.46-1.00).CONCLUSION:Our analysis indicated that microsphere embolization was associated with superior survival and treatment response in comparison with c-TACE in the treatment of patients with HCC.