scholarly journals Chemotherapy Effectiveness and Prognosis of Gastric Cancer Influenced by PTPN11 Polymorphisms

2016 ◽  
Vol 39 (4) ◽  
pp. 1537-1552 ◽  
Author(s):  
Chuanjun Zhuo ◽  
Mingjing Shao ◽  
Ce Chen ◽  
Chongguang Lin ◽  
Deguo Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Fold Increase ◽  
Axillary Lymph Node Metastasis ◽  
Axillary Lymph ◽  
Nucleotide Polymorphisms ◽  
Positive Interaction ◽  
Kaplan Meier ◽  
Pcr Rflp ◽  
Differentiation Degree ◽  
H Pylori

Objective: Since gastric cancer (GC) cells exhibited higher grades of SHP-2 encoded by PTPN11 than normal cells, it would be intriguing to explore whether PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy effectiveness and GC prognosis among a Chinese population. Methods: Altogether 430 late-stage GC patients and 960 healthy controls matched with age and sex were incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4 cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. Survival curves were plotted with Kaplan-Meier method and the COX proportional hazard model was used to analyze independent factors for GC prognosis. Results: For rs12229892, AA and GA genotypes would cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60; 95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly associated with a decrease in the risk of GC when compared with G allele (OR = 0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle chemotherapy suggested that chemotherapy was significantly more effective for GA and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides, the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking, family history, intake of processed food and H .pylori infection) on GC risk was considered as positive interaction, while that of rs2301756 (AA) and the above parameters was deemed as negative interaction. Finally, differentiation degree, axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent risk factors for GC development (all P < 0.05). Conclusion: Since rs2301756 polymorphism of PTPN11 was associated with reduced risk of GC and better effects of chemotherapy on GC, it can be considered as a predictor of GC prognosis and the treatment target for GC.

scholarly journals Risk assessment of pathological conditions caused by circulating H. pylori strains

2020 ◽  
Vol 46 (1) ◽  
pp. 60-64
Author(s):  
D. K. Karimova ◽  
G. N. Sobirova ◽  
M. M. Karimov
Keyword(s):  
Gastric Cancer ◽  
Repetitive Sequences ◽  
Fold Increase ◽  
Caga Gene ◽  
Repetitive Region ◽  
Polymorphic Gene ◽  
C Segments ◽  
H Pylori ◽  
Gastroduodenal Zone ◽  
Gene Data

In recent years, there has been an increase in the prevalence of inflammatory and destructive diseases of the gastroduodenal zone, which is primarily explained by Helicobacter pylori (H. pylori) infection. One of the main factors of H. pylori pathogenicity is presence of cytotoxin-associated gene — CagA. It is known that CagA-positive H. pylori strains are associated with the development of atrophy, tumor invasion and rapid metastasis. A number of recently published studies have revealed that CagA is a polymorphic gene which contains a different number of repetitive sequences located in the 3’ region. Each repetitive region of CagA contains Glu-Pro-Ile-Tyr-Ala (EPIYA) profiles including tyrosine phosphorylation. Depending on the sequence of the EPIYA profile, there are 4 segments: EPIYA-A, EPIYA-B, EPIYA-C, EPIYA-D, each containing a repetitive region. Geographical features of the prevalence of H. pylori strains depending on the sequence of EPIYA have been revealed: EPIYA-A region of the western isolates of this bacterium is associated with EPIYA-A, EPIYA-B, EPIYA-C segments, while the eastern CagA-positive H. pylori isolates are characterized by the A-B-D type of the CagA gene. Data illustrating the strong correlation between the western CagA-positive H. pylori strains, which have a repeating EPIYA-C segment, and the development of precancerous states, as well as gastric cancer, are presented. H. pylori strains containing simultaneously A-B motives of EPIYA or one C-type of the CagA gene are associated with a 7-fold increase of risk of gastric cancer compared to CagA-negative strains; presence of two or more EPIYA-C motives is associated with a 30-fold increase of this risk.

Using NSG recipient mice improves engraftment of gastric cancer patient derived xenografts.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 70-70
Author(s):  
Sam C. Wang ◽  
Min Zhu ◽  
Ibrahim Nassour ◽  
Jeanne Shen ◽  
John C. Mansour ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Liver Metastases ◽  
Expression Profiles ◽  
Management Strategies ◽  
Axillary Lymph Node Metastasis ◽  
Post Treatment ◽  
Clinical Samples ◽  
Axillary Lymph ◽  
Nsg Mice ◽  
The One

70 Background: Previous gastric cancer (GC) patient derived xenograft (PDX) studies reported engraftment rates inversely proportional to the immunocompromised states of recipient mice (nudes 17%, scid 27%, and NOD/ scid 34%). We tested highly immunocompromised NOD scidgamma (NSG) mice, which lack mature T cells, B cells, or functional natural killer cells, as recipients for low volume biopsies and post-treatment GC samples. Methods: Consent was obtained from GC patients who were scheduled to undergo esophagogastroduodenoscopy (EGD) and diagnostic laparoscopy as part of their disease management strategies. The following amounts of tumor were coated with Matrigel and inoculated into the flanks of NSG mice: EGD biopsies ~10 mg, post-treatment samples ~100 mm3, and peritoneal metastasis biopsies ~100 mm3. Tumors were serially measured and passaged when the greatest dimension reached 1.5 cm, or if there was overlying skin necrosis. Results: The engraftment rates were: EGD biopsies 48% (13 of 27 samples), post-resection samples 58% (7 of 12), and peritoneal metastases 11% (1 of 9). Median time to first passage was 10.1 weeks (range: 8.1 to 12.4) for EGD biopsies and 22.1 weeks (9.6 to 33.0) for post-treatment samples. Two (15%) engrafted EGD mice developed liver metastases, and one (7.7%) had axillary lymph node metastasis (AxLN). Three (47%) engrafted post-treatment mice had liver metastases and two (29%) had AxLN. Histology was generally maintained through passages and metastases with some loss of mucinous components. There were no associations between engraftment rate and any evaluated clinical or pathologic characteristics, including tumor response and overall survival. The tumor from the one patient who had a complete pathologic response after NAT did not engraft. Conclusions: Using highly immunocompromised NSG mice improved engraftment rates of GC PDX, even for challenging specimens such as endoscopic biopsies and post-treatment resection samples. Peritoneal biopsies did not engraft well. Tumor histology was generally maintained through passages. Studies comparing the expression profiles of serially passaged tumors to the original clinical samples are ongoing.

scholarly journals Association Analysis between SNPs in LATS1 and LATS2 and Non-Cardia Gastric Cancer

2020 ◽  
Author(s):  
Licong Ma ◽  
Xuyang Tian ◽  
Fang Gao ◽  
Wenjie Dong ◽  
Tong Dang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protective Factor ◽  
Serological Test ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Large Tumor ◽  
Additive Inheritance ◽  
And Gender ◽  
H Pylori ◽  
Control Association

Abstract Background: Many studies have found that large tumor suppressor kinase 1 (LATS1) and LATS2 play important roles in many diseases, but studies have been rare on the relationship between these genes and non-cardia gastric cancer (GC). We performed a case-control association study to investigate the associations between single nucleotide polymorphisms (SNPs) in LATS1 and LATS2 genes and Helicobacter pylori (H. pylori) infection as well as the risk of non-cardia GC. Methods: First, H. pylori infection was determined by the serological test using enzyme-linked immunoassay. Then genotyping of SNPs was performed for 808 samples by the Taqman method. Finally, unconditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age and gender, for the association of each SNP with the infection of H. pylori, the risk of non-cardia gastric cancer, as well as the expression of LATS1 and LATS2 proteins in non-cardia GC tissues, using the codominant, dominant, recessive, overdominant, and additive inheritance models, respectively. Results: The statistical results showed that LATS2 rs9552315 was associated with H. pylori infection, and the CC+CT genotype could reduce the risk of H. pylori infection (odds ratio [OR]: 0.549, 95% confidence interval [CI]: 0.339–0.881, P<0.05) compared with the TT genotype in a dominant model. LATS1 rs9393175 was associated with the risk of non-cardia GC, and the AG genotype reduced the risk of non-cardia GC (OR: 0.702, 95% CI: 0.516–0.952, P<0.05) compared with the GG+AA genotype in an overdominant model. LATS2 rs9509492 was associated with the risk of GC in an additive model. No associations were found between five SNPs and expression of LATS1 and LATS2 proteins in non-cardia GC tissue. Conclusions: LATS2 rs9552315 CT genotype may be a protective factor against infection of H. pylori. LATS1 rs9393175 AG genotype and LATS2 rs9509492 GG genotype may be protective factors for non-cardia GC.

scholarly journals Antioxidant-Rich Diet, GSTP1 rs1871042 Polymorphism, and Gastric Cancer Risk in a Hospital-Based Case-Control Study

2021 ◽  
Vol 10 ◽  
Author(s):  
Jimi Kim ◽  
Hyejin Kim ◽  
Jeonghee Lee ◽  
Il Ju Choi ◽  
Young-Il Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Risk ◽  
Genetic Variants ◽  
Total Phenolics ◽  
Nucleotide Polymorphisms ◽  
Gastric Cancer Risk ◽  
Glutathione S Transferase ◽  
Dietary Antioxidant ◽  
H Pylori ◽  
Gastric Cancer Patients

BackgroundChronic gastritis along with Helicobacter pylori (H. pylori) infection has been implicated in inflammatory response-related genes linked to the causation of gastric cancer. Glutathione S-transferase Pi (GSTP1) plays a role in regulating oxidative stress and detoxification against carcinogenesis. In this study, we aimed to determine whether an antioxidant-rich diet is associated with gastric cancer risk and identify how this association could be altered by GSTP1 genetic variants.MethodsThis study included 1,245 participants (415 cases and 830 controls) matched for age and sex. The dietary antioxidant capacity was estimated based on the oxygen radical absorbance capacity (ORAC) incorporated with a semiquantitative food frequency questionnaire. Five single nucleotide polymorphisms (SNPs) of GSTP1 (rs1695, rs749174, rs1871042, rs4891, and rs947895) were selected among the exome array genotype data.ResultsHigh dietary ORAC was inversely associated with gastric cancer (hydrophilic ORAC OR T3vs. T1, 95% CI = 0.57, 0.39–0.82, P = 0.004; lipophilic ORAC = 0.66, 0.45–0.95, P = 0.021; total phenolics = 0.57, 0.39–0.83, P = 0.005). The polymorphism rs1871042 increased the risk of gastric cancer (OR, 95% CI = 1.55, 1.10–2.16, P = 0.01, CT+TT vs. CC). A remarkably reduced risk of gastric cancer was observed among those who had a high dietary ORAC according to rs1871042 polymorphism (hydrophilic ORAC OR T3vs. T1, 95% CI = 0.36, 0.17–0.78, P for trend = 0.013; lipophilic ORAC = 0.58, 0.37–0.93, P for trend = 0.021; total phenolics = 0.38, 0.17–0.83, P for trend = 0.019).ConclusionsOur findings indicate that dietary ORAC intake may be inversely associated with the risk of gastric cancer altered by genetic variants of GSTP1, providing new intervention strategies for gastric cancer patients.

THE ASSOCIATION OF THE COMBINATION OF TP53 GENE CODON 72 POLYMORPHISM AND HELICOBACTER PYLORI INFECTION WITH GASTRIC CANCER

2017 ◽  
pp. 47-52
Author(s):  
Thi Minh Thi Ha ◽  
Van Huy Tran ◽  
Viet Nhan Nguyen
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Risk Factor ◽  
Tp53 Gene ◽  
Codon 72 ◽  
Codon 72 Polymorphism ◽  
Pcr Rflp ◽  
Two Factors ◽  
Risk Patients ◽  
H Pylori

Background: The interaction of environment factor and host factor plays the important role in the pathogenesis of gastric cancer (GC). This study aimed to evaluate the association of the combination of TP53 gene codon 72 polymorphism and the H. pylori infection with GC risk. Patients and methods: 112 patients with GC and 136 patients without GC were extracted DNA from specimens of gastric mucosa, then were determined TP53 gene codon 72 polymorphism by PCR-RFLP and diagnosed H. pylori infection by PCR with ureC gene-specific primers. Results: There was no significant association between TP53 gene codon 72 polymorphism and GC risk, as well as between H. pylori infection and GC risk. The combination of two factors (TP53 gene codon 72 polymorphism and H. pylori infection) was found to be associated with GC risk: The combination of Pro/Pro genotype and H. pylori (+) was the GC risk factor, OR = 2.62 (95%CI: 1.20–5.71) as compared to other combinations. In the group of H. pylori-positive patients, Pro/Pro genotype was the GC risk factor, OR = 2.42 (95%CI: 1.05 – 5.59) as compared to (Arg/Arg + Arg/Pro) group, and OR = 3.48 (95%CI: 1.23 – 9.78) as compared to Arg/Arg genotype. Conclusion: The factors of TP53 gene codon 72 polymorphism and H. pylori infection were not associated with GC risk as assessed separately, but they had the interaction associated with GC risk. Key words: TP53 gene codon 72 polymorphism, Helicobacter pylori, gastric cancer

Antioxidant-rich diet, GSTP1 rs1871042 polymorphism, and gastric cancer risk in a hospital-based case-control study

2020 ◽  
Author(s):  
Jimi Kim ◽  
Hyejin Kim ◽  
Jeonghee Lee ◽  
Il Ju Choi ◽  
Young-Il Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Case Control Study ◽  
Total Phenolics ◽  
Nucleotide Polymorphisms ◽  
Gastric Cancer Risk ◽  
Glutathione S Transferase ◽  
Single Nucleotide ◽  
Dietary Antioxidant ◽  
H Pylori ◽  
Control Study

Abstract Background Chronic gastritis along with Helicobacter pylori (H. pylori) infection has been implicated in inflammatory response-related genes linked to the causation of gastric cancer (GC). Glutathione S-transferase Pi (GSTP1) plays a role in regulating oxidative stress and detoxification against carcinogenesis. In this study, we aimed to determine whether an antioxidant-rich diet was associated with GC risk and to identify how the association could be altered by GSTP1 genetic variants. Methods The study was conducted with 1,245 participants (415 cases and 830 controls) matched for age and sex. Dietary antioxidant capacity was estimated based on oxygen radical absorbance capacity (ORAC) incorporated with a semiquantitative food frequency questionnaire. Five single nucleotide polymorphisms (SNPs) of GSTP1 (rs1695, rs749174, rs1871042, rs4891, and rs947895) were selected among the exome array genotype data. Results High dietary ORAC showed inverse associations with GC (hydrophilic ORAC OR T3 vs. T1, 95% CI = 0.57, 0.39–0.82, P = 0.004; lipophilic ORAC = 0.66, 0.45–0.95, P = 0.021; total phenolics = 0.57, 0.39–0.83, P = 0.005). The polymorphism of rs1871042 increased GC risk (OR, 95% CI = 1.55, 1.10–2.16, P = 0.01, CT + TT vs. CC). A remarkably reduced risk of GC was observed among those who had a high dietary ORAC according to rs1871042 polymorphism (hydrophilic ORAC OR T3 vs. T1, 95% CI = 0.36, 0.17–0.78, P for trend = 0.013; lipophilic ORAC = 0.58, 0.37–0.93, P for trend = 0.021; total phenolics = 0.38, 0.17–0.83, P for trend = 0.019). Conclusions Our findings indicate that the association between dietary ORAC intake and GSTP1 polymorphisms as they pertain to the risk of GC may present new intervention strategies for GC patients.

scholarly journals Association of Interleukin-8 with Cachexia from Patients with Low-Third Gastric Cancer

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Bo Song ◽  
Dianliang Zhang ◽  
Shuchun Wang ◽  
Hongmei Zheng ◽  
Xinxiang Wang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cachexia ◽  
Haplotype Analysis ◽  
Positive Association ◽  
Serum Levels ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Pcr Rflp ◽  
Polymerase Chain

Background. Interleukin (IL)-8 has been implicated in the development of cancer cachexia. The polymorphism of IL-8 gene, which may affect the production level of IL-8, may be associated with cancer cachexia.Methods. The serum IL-8 level in our study was examined by radioimmunoassay. We also analyzed single nucleotide polymorphisms (SNPs) −251 A/T and +781 C/T of IL-8 gene, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results. The serum levels of IL-8 were significantly elevated in patients with low-third gastric cancer compared with controls, and were further up-regulated in patients with cachexia than those without (Z=−3.134,P=.002). A significantly increased frequency of +781 T allele was noted in patients with cachexia (OR=2.247, 95% CI: 1.351–3.737,P=.002). The +781 TT genotype was observed to be associated with a significantly increased risk of cachexia (OR=3.167, 95% CI: 1.265–7.929,P=.011), and with odds ratio of 3.033 (95% CI: 1.065–8.639,P=.038) for cachexia after adjusting for potential confounding factors. Meanwhile, haplotype analysis indicated a borderline positive association betweenT251T781haplotype and cachexia as compared with theT251C781haplotype (OR=4.92, 95% CI: 1.00–24.28;,P=.053).Conclusions. IL-8 appears to be associated with cachexia from patients with low-third gastric cancer.

scholarly journals A Distinct Clinicopathological Feature and Prognosis of Young Gastric Cancer Patients Aged ≤ 45 Years Old

2021 ◽  
Vol 11 ◽  
Author(s):  
Qian Huang ◽  
Xiufeng Zheng ◽  
Yang Jiao ◽  
Yanna Lei ◽  
Xiaoying Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Late Onset ◽  
Radical Resection ◽  
Palliative Surgery ◽  
Clinicopathological Feature ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Differentiation Degree ◽  
Gastric Cancer Patients

PurposeThe aim of this retrospective study was to probe into clinicopathological features and prognosis of early-onset gastric cancer (EOGC) patients aged ≤ 45 years old.MethodsThis study selected 154 young gastric cancer patients aged ≤ 45 years old and 158 elderly gastric cancer patients aged &gt; 50 years old admitted to West China Hospital of Sichuan University in 2009-2019 as the research object. These patients were further divided into two groups according to whether tumor can be resected radically. The following parameters were analyzed: age, gender, helicobacter pylori (HP) infection status, Her-2 status, pathological type and stage, chemotherapy, tumor differentiation degree, overall survival (OS).ResultsMore than 3,000 patients with gastric carcinoma were screened, and 154 young gastric cancer patients aged ≤ 45 years old were identified as EOGC. Among them, the number of female patients in EOGC group was significantly higher than that of males, accounting for 63.6%. In addition, EOGC were associated with diffuse Laur´en type and poorly differentiated tumors. Interestingly, the Kaplan–Meier method showed that the OS of unresectable EOGC group was significantly lower than that of unresectable LOGC group (P = 0.0005) and chemotherapy containing paclitaxel tended to be more effective in the young people (P = 0.0511). Nevertheless, there was no significant difference in OS between young and elderly patients with gastric cancer in the radical resection group (P = 0.3881).ConclusionEOGC patients have a worse prognosis than late-onset gastric cancer (LOGC) patients with advanced unresectable gastric cancer. Palliative surgery or chemotherapy containing paclitaxel may improve the OS of unresectable young individuals with gastric cancer. Additional randomized controlled trials are required for guiding clinical practice.

scholarly journals Systematic Characterization of Prognostic Values of Peroxiredoxin Family in Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Rui Xu ◽  
Jiadong Pan ◽  
Jie Mei ◽  
Qinglin Zhang
Keyword(s):  
Gastric Cancer ◽  
Treatment Strategies ◽  
Clinical Information ◽  
Prognostic Assessment ◽  
Kaplan Meier ◽  
Status Differentiation ◽  
Differentiation Degree ◽  
Km Plotter ◽  
Expression Status

The peroxiredoxin (PRDX) gene family has been reported to participate in regulating occurrence and development of cancerous diseases, but its exact prognostic values in gastric cancer (GC) remain largely elusive. In the current research, we evaluated the prognostic value in predicting overall survival (OS) of each individual PRDX mRNA expression based on patients’ cohorts from the Kaplan–Meier (KM) plotter database, which contains clinical information and gene expression data obtained from a total of 876 GC patients. Our results revealed that mRNA expressions of PRDX1, PRDX2, PRDX3, and PRDX4 were significantly associated with worse OS in GC patients, whereas PRDX5 and PRDX6 mRNA expressions were not associated with OS in GC patients. In addition, the prognostic values of PRDXs in the different clinicopathological features according to clinical stages, Lauren classifications, HER2 expression status, differentiation degree, and treatment strategies of GC patients were further evaluated in the KM plotter database. As a result, more potential beneficiaries who may benefit from prognostic assessment using PRDX mRNA expressions were identified. Our results elucidated the exact values of PRDXs in assessing GC prognosis and might provide primary evidence for further study on the mechanism of PRDXs participating in occurrence and development of GC.

scholarly journals Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Alejandra Sandoval-Bórquez ◽  
Kathleen Saavedra ◽  
Gonzalo Carrasco-Avino ◽  
Benjamin Garcia-Bloj ◽  
Jacqueline Fry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Regulation Of Gene Expression ◽  
Nucleotide Polymorphisms ◽  
Primary Tumors ◽  
Barr Virus ◽  
Geographical Regions ◽  
Epstein Barr ◽  
H Pylori ◽  
Potential Biomarkers

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection byHelicobacter pylori(H. pylori) and Epstein-Barr virus (EBV), host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade.

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