Polymorphisms of interleukin-10 promoter are not associated with prognosis of advanced gastric cancer

AIM: To evaluate the association between of the interleukin-10 (IL-10) promoter polymorphisms and survival of advanced gastric cancer (GC) patients. METHODS: The IL-10 (-1082, rs1800896; -819, rs1800871; and-592, rs1800896) genotypes in 234 patients with advanced gastric cancer and in 243 healthy controls were determined by polymerase chain reaction-restriction fragment length polymorphism assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression for the ...     

Lethal-7-related polymorphisms are associated with susceptibility to and prognosis of gastric cancer

BACKGROUND The lethal-7(let-7)family members and their targets are involved in the development and progression of tumors.Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis.In gastric cancer,however,the related studies are limited.AIM To investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population.METHODS A total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013.Gastric cancer patients were followed periodically.Ten single nucleotide polymorphisms(SNPs)in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed.RESULTS All the ten SNPs were in Hardy-Weinberg equilibrium.The C allele of the rs3811463 polymorphism in the 3’-untranslated region(UTR)of LIN28A was associated with a lower risk of gastric cancer[odds ratio(OR)=0.74,95%confidence interval(CI):0.61-0.88,P=0.001]after adjustment for age and Helicobacter pylori status.Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9%(95%CI:50.1%-57.6%).The rs10889677 in the 3’-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner,in which the death risk increased by 25%[hazard ratio(HR)=1.25,95%CI:1.04-1.45,P=0.011]with each increase in the number of C alleles after controlling for other potential clinicopathological parameters.CONCLUSION The let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.     

Cytoplasmic expression of p27(kip1) is associated with a favourable prognosis in colorectal cancer patients

INTRODUCTION p27, also known as Kip1, is expressed in most cells and its role is to bind and inhibit cyclin/cyclin-dependent kinase (cyclin-CDK) complexes, thereby inhibiting cell cycle progression[1]. This role in the cell cycle makes p27kip1 a key playe…     

High D-dimer levels are associated with poor prognosis in cancer patients

Background

Systemic activation of hemostasis is frequently observed in cancer patients, even in the absence of thrombosis. Moreover, this activation has been implicated in tumor progression, angiogenesis and metastatic spread. Increased levels of D-dimer, which is a degradation product of cross-linked fibrin, indicate a global activation of hemostasis and fibrinolysis.

Design and Methods

In a prospective and observational cohort study, we assessed the prognostic value of D-dimer levels for overall survival and mortality risk in 1178 cancer patients included in the Vienna Cancer and Thrombosis Study (CATS). Patients were followed over 2 years at regular intervals until occurrence of symptomatic venous thromboembolism or death. D-dimer levels were measured with a quantitative D-dimer latex agglutination assay

Results

The main solid tumors were malignancies of the lung (n=182), breast (n=157), lower gastrointestinal tract (n=133), pancreas (n=74), stomach (n=50), kidney (n=37), prostate (n=133), and brain (n=148); 201 of the patients had hematologic malignancies; 63 had other tumors. During a median follow-up of 731 days, 460 (39.0%) patients died. The overall survival probabilities for patients with D-dimer levels categorized into four groups based on the 1^st, 2^nd and 3^rd quartiles of the D-dimer distribution in the total study population were 88%, 82%, 66% and 53% after 1 year, and 78%, 66%, 50% and 30% after 2 years, respectively (P<0.001). The univariate hazard ratio of D-dimer (per double increase) for mortality was 1.5 (95% confidence interval: 1.4–1.6, P<0.001) and remained increased in multivariable analysis including tumor subgroups, age, sex and venous thromboembolism.

Conclusions

High D-dimer levels were associated with poor overall survival and increased mortality risk in cancer patients.     

胃癌患者术后端粒长度变化与预后观察

目的分析原发性胃癌组织中的端粒长度变化与患者术后预后的关系.方法以琼脂糖DNA杂交检测58例手术切除的原发性胃癌与邻近胃组织中端粒限制性内切酶片段(TRF)的长度,并观察术后患者的临床状况及生存期.结果发现原发性胃癌组织中的平均TRF长度均比相应邻近胃组织缩短.其中原发性胃癌有14例TRF缩短,5例TRF延长;且在胃癌中TRF的这种异常状态与肿瘤的大小、转移、临床病理分期及患者的生存率相一致.结论 TRF长度不仅参与了胃癌的发生与发展,而且也为胃癌的诊断及预后判断提供了一种新的手段.     

Association of pseudoachalasia with advancing cancer of the gastric cardia.

BACKGROUND: Pseudoachalasia is attributable to malignant tumors of the gastric cardia in more than 50% of cases. Study of the progression of esophageal manometric abnormalities with increasing tumorous involvement of the esophagogastric junction may improve our understanding of the pathophysiologic characteristics of pseudoachalasia. METHODS: During a 2-year period, esophageal manometric characteristics were evaluated for 17 of 21 consecutive patients with cancer of the gastric cardia. Manometry was not possible in the other four. Manometric parameters assessed included lower esophageal sphincter pressure, percentage lower esophageal sphincter relaxation, and percentage failed peristalsis. The extent of malignant involvement of the esophagogastric junction was graded as none, less than 50% of the circumference, or 50% or more of the circumference, assessed from surgical specimens in 13 cases and endoscopy in 4 cases. RESULTS: Pseudoachalasia was diagnosed in 3 cases, all with 50% or greater circumferential involvement of the esophagogastric junction. The first manometric indication of evolving pseudoachalasia was impaired lower esophageal sphincter relaxation; loss of peristaltic function was a secondary consequence. CONCLUSIONS: These findings suggest that the primary mechanism of pseudoachalasia with gastric cardia cancer is malignant stenosis of the esophagogastric junction.     

Tetraspanin CD151 expression associated with prognosis for patients with advanced gastric cancer

Purpose

Tetraspanin CD151 is known to be involved in cancer invasion and metastasis, and its overexpression appears to be associated with a poor prognosis for various types of cancer. However, the expression status of CD151 and its prognostic impact in advanced gastric cancer (AGC) has not yet been clarified.

Methods

Immunohistochemistry was used to investigate the expression of CD151, c-erbB2, and c-Met in 159 cases of AGC. The clinicopathological and prognostic significance of these biomarkers were then evaluated.

Results

The overexpression of CD151 was observed in a subset of advanced gastric adenocarcinomas (25.8 %), and c-erbB2 and c-Met were overexpressed in 15.1 and 35.2 % of the cohort, respectively. CD151 overexpression was more frequently observed in tumors from younger patients (P = 0.028). There were close associations between CD151 and c-erbB2 overexpression (P = 0.033) and between c-erbB2 and c-Met overexpression (P = 0.001). CD151 overexpression was closely correlated with patient’ overall survival (OS; P < 0.001) and disease-free survival (DFS; P < 0.001). Furthermore, the expression rate of CD151 seemed to increase gradually according to the depth of invasion (T stage) (χ ² test for trend; P = 0.101), N stage (P = 0.238), and pathologic stage (P = 0.153), although trends were not statistically significant. In a multivariate analysis, CD151 overexpression was an independent prognostic factor predicting worse OS (P = 0.002) and DFS (P = 0.005), along with the T and N stage.

Conclusions

CD151 was found to be an independent prognostic marker for patients with AGC.     

Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer

In a recent report, [Zhang et al. (2003) N. Engl. J. Med. 348, 203-213], the presence of CD3+ tumor-infiltrating lymphocytes (TILs) was found to correlate with improved survival in epithelial ovarian cancer. We performed immunohistochemical analysis for TILs and cancer testis antigens in 117 cases of epithelial ovarian cancer. The interrelationship between subpopulations of TILs and expression of cancer testis antigens was investigated, as well as between TILs and overall survival. The median follow-up of the patients was 31 months. Patients with higher frequencies of intraepithelial CD8+ T cells demonstrated improved survival compared with patients with lower frequencies [median = 55 versus 26 months; hazard ratio = 0.33; confidence interval (C.I.) = 0.18-0.60; P = 0.0003]. No association was found for CD3+ TILs or other subtypes of intraepithelial or stromal TILs. However, the subgroups with high versus low intraepithelial CD8+/CD4+ TIL ratios had median survival of 74 and 25 months, respectively (hazard ratio = 0.30; C.I. = 0.16-0.55; P = 0.0001). These results indicate that CD4+ TILs influence the beneficial effects of CD8+ TIL. This unfavorable effect of CD4+ T cells on prognosis was found to be due to CD25+ forkhead box P3 (FOXP3)+ regulatory T cells (Treg; suppressor T cells), as indicated by survival of patients with high versus low CD8+/Treg ratios (median = 58 versus 23 months; hazard ratio = 0.31; C.I. = 0.17-0.58; P = 0.0002). The favorable prognostic effect of intraepithelial CD8+ TILs did not correlate with concurrent expression of NY-ESO-1 or MAGE antigens. We conclude that intraepithelial CD8+ TILs and a high CD8+/Treg ratio are associated with favorable prognosis in epithelial ovarian cancer.     

Health disparities are associated with gastric cancer mortality-to-incidence ratios in 57 countries

AIM To evaluate the association between mortality-to-incidence ratios(MIRs) and health disparities.METHODS In this study, we used the GLOBOCAN 2012 database to obtain the cancer incidence and mortality data for 57 countries, and combined this information with the World Health Organization(WHO) rankings and total expenditures on health/gross domestic product(e/GDP). The associations between variables and MIRs were analyzed by linear regression analyses and the 57 countries were selected according to their data quality. RESULTS The more developed regions showed high gastric cancer incidence and mortality crude rates, but lower MIR values than the less developed regions(0.64 vs 0.80, respectively). Among six continents, Oceania had the lowest(0.60) and Africa had the highest(0.91) MIR. A good WHO ranking and a high e/GDP were significantly associated with low MIRs(P = 0.001 and P = 0.001, respectively).CONCLUSION The MIR variation for gastric cancer would predict regional health disparities.     

ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population

AIM:To evaluate the association between the geneticpolymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.METHODS:The study subjects were 477 age-and sex-matched case-control pairs.Genotyping was performed for 15 single nucleotide polymorphisms(SNPs)in ITGA1.The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models.Multiple testing corrections were carried out following methodology for controlling the false discovery rate.Gene-based association tests were performed using the versatile gene-based association study(VEGAS)method.RESULTS:In the codominant model,the ORs for SNPs rs2432143(1.517;95%CI:1.144-2.011)and rs2447867(1.258;95%CI:1.051-1.505)were statistically significant.In the dominant model,polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors,with ORs of 1.337(95%CI:1.029-1.737)and 1.412(95%CI:1.061-1.881),respectively.In the recessive model,only the rs2432143 polymorphism was significant(OR=1.559,95%CI:1.150-2.114).The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model(OR=0.602,95%CI:0.212-0.709,P=0.021)and the dominant model(OR=0.653,95%CI:0.483-0.884).The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.In the dominant model,the A-T type of ITGA1 haplotype block 2 was a significant risk factor(OR=1.341,95%CI:1.034-1.741).SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and,thus,to the risk of developing gastric cancer.CONCLUSION:ITGA1 gene SNPs rs1862610,rs2432143,and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.     

Heat shock protein 22 overexpression is associated with the progression and prognosis in gastric cancer

Purpose

The heat shock protein 22 (HSP22) is associated with tumor proliferation and protects tumor cell from apoptosis in many malignancies. However, the role of HSP22 in gastric cancer has not been thoroughly elucidated. The aim was to determine the relationship of HSP22 expression with clinicopathological parameters and prognosis in gastric cancer and estimate the alteration of HSP22 expression after neoadjuvant chemotherapy.

Methods

HSP22 and matrix metallopeptidase 9 (MMP-9) antigen expressions were evaluated by immunohistochemistry in 129 gastric carcinoma samples. Univariate and multivariate analyses were performed to determine the association between HSP22 expression and prognosis. The response of HSP22 was assessed in 47 patients who received neoadjuvant chemotherapy.

Results

HSP22 protein expression was significantly associated with tumor size, depth invasion, lymph node metastasis and stage of disease (all P < 0.05). In univariate and multivariate analyses, HSP22 was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS) (P = 0.003 and P = 0.004, respectively). Furthermore, HSP22 overexpression was associated with a poor prognosis in all patients and in patients subgroups stratified by tumor size, depth invasion and lymph node metastasis. In addition, HSP22 was significantly correlated with MMP-9 among 129 gastric cancer tissues (P < 0.001). Patients who had MMP-9 overexpression had poor OS and shorter RFS. Moreover, the alteration of HSP22 was not comparable in 47 patients who underwent neoadjuvant chemotherapy.

Conclusions

HSP22 plays an important role on tumor aggressiveness and prognosis and may act as a promising target for prognostic prediction.     

Myofibrillogenesis regulator-1 overexpression is associated with poor prognosis of gastric cancer patients

AIM: To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer. METHODS: In our previous study of human wholegenome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records. RESULTS: MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stageⅠ-Ⅳ carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27 mo (95%CI: 13.41-115.13) and 16.77 mo (95%CI: 8.80-24.74). Univariate and multivariate analyses were performed to compare the impact of MR-1 expression and other clinicopathological parameters on prognosis. In a univariate analysis on all 70 specimens, 6 factors were found to be significantly associated with the overall survival statistically: including MR-1 expression, depth of invasion, distant metastasis, lymph node metastasis, vascular invasion and the tumor node metastasis (TNM) stage based on the 7th edition of the International Union against Cancer TNM classification. To avoid the influence caused by univariate analysis, the expressions of MR-1 as well as other parameters were examined in multivariate Cox analysis. Clinicopathological variables that might affect the prognosis of gastric cancer patients were analyzed by Cox regression analysis, which showed that MR-1 expression and TNM stage were independent predictors of postoperative survival. The best mathematical multivariate Cox regression model consisted of two factors: MR-1 expression and TNM stage. Our results indicated that MR-1 protein could act as an independent marker for patient overall survival [Hazard ratio (HR): 2.215, P = 0.043]. CONCLUSION: MR-1 is an important variable that can be used to evaluate the outcome, prognosis and targeted therapy of gastric cancer patients.     

Genes inside the cagPAI of Helicobacter pylori are not associated with gastric cancer in Japan

BACKGROUND/AIMS: In Japan, infection with cagA-positive H. pylori is not associated with gastric cancer unlike Western populations. Both cagE and Agrobacterium VirD4 homologue are genes inside the cagPAI. The aim of this study was to examine whether the presence of genes inside the cagPAI, cagA, cagE and Agrobacterium VirD4 homologue, is associated with gastric cancer in Japan. METHODOLOGY: Thirty-nine patients with gastric cancer and 39 subjects with only chronic gastritis were infected with H. pylori. Seventy-eight H. pylori strains were isolated from gastric biopsies and the presence of 23S rRNA, cagA, cagE, and VirD4 homologue were studied by polymerase chain reaction. RESULTS: The positivity of cagA was 97.4% in patients with gastric cancer, and 92.3% in control subjects. Thirty-six strains (92.3%) isolated from patients and 35 strains (89.7%) from control subjects had both cagE and VirD4. All the 3 cagA-negative strains did not have both cagE and VirD4. There were no significant differences in the positivities of cagA, cagE, and VirD4 between patients and control subjects. CONCLUSIONS: cagE and VirD4 were possessed by most Japanese strains, and thus the structure of the cagPAI of H. pylori might not be associated with the development of gastric cancer in Japan.