scholarly journals The Clinicopathological Features and Genetic Mutations in Gastric Cancer Patients According to EMAST and MSI Status

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 551
Author(s):  
Wen-Liang Fang ◽  
Ming-Huang Chen ◽  
Kuo-Hung Huang ◽  
Shih-Ching Chang ◽  
Chien-Hsing Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Repair ◽  
Survival Rate ◽  
Cancer Patients ◽  
Clinicopathological Features ◽  
Akt Pathway ◽  
Genetic Mutations ◽  
Tetranucleotide Repeats ◽  
Gastric Cancer Patients ◽  
T Category

Background: There has been no report regarding the clinicopathological features and genetic mutations regarding elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in gastric cancer (GC). Methods: The correlation among EMAST status, microsatellite instability (MSI) status, mutations of common GC-related genes and 16 DNA repair-associated genes, and the clinicopathological features were analyzed. Results: Among the 360 GC patients enrolled, there were 76 (21.1%) with EMAST+ tumors and 284 with EMAST− tumors, and 59 (16.4%) were MSI-high (MSI-H) tumors, and 301 were microsatellite stable (MSS) tumors. Patients with EMAST+ tumors exhibited an earlier pathological T category and had more genetic mutations in the PI3K/AKT pathway, ARID1A and DNA repair-associated genes than those with EMAST− tumors. Patients with MSI-H tumors have more genetic mutations in the PI3K/AKT pathway and DNA repair-associated genes than those with MSS tumors. In the subgroup analysis for MSI-H GC, EMAST+ tumors were associated with earlier pathological T and N categories, earlier TNM stages, higher frequency of DNA-repair-associated genetic mutations, and a better survival rate than EMAST− tumors. Conclusions: PI3K/AKT pathway mutations may play an important role in EMAST+ and/or MSI-H GC. EMAST+/MSI-H tumors seem to represent a different subtype of gastric cancer from EMAST−/MSI-H tumors.

scholarly journals Helicobacter pylori infection reduces likelihood of death from advanced cancer: A longitudinal analysis from the Japanese DAIKO prospective cohort study

2021 ◽  
Author(s):  
Satoshi S. Nishizuka ◽  
Masahiro Nakatochi ◽  
Yuka Koizumi ◽  
Asahi Hishida ◽  
Rieko Okada ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Incidence ◽  
Prospective Cohort ◽  
Factors Associated ◽  
Cancer Death Rate ◽  
Gastric Cancer Patients ◽  
Advanced Stage Cancer

AbstractBackgroundParadoxically, patients with advanced stomach cancer who are Helicobacter pylori-positive (HP+) have a higher survival rate than those who are HP-. This finding suggests that HP infection has beneficial effects for cancer treatment. Present study examines whether HP+ individuals have a lower likelihood of death from cancer than those who are HP-.Methods and findingsProspective cohort data (n = 4,982 subjects enrolled in the DAIKO study between 2008-2010) was used to assess whether anti-HP antibody status as a surrogate for past-present HP infection was associated with cancer incidence. The median age in the primary registry was 53 years-old (range 34-69 years-old). Over the 8-year observation period there were 234 (4.7%) cancer cases in the cohort and 88 (1.8%) all-cause deaths. Urine anti-HP antibody data was available for all but one participant (n = 4,981; 99.97%). The number of HP+ and HP- individuals was 1,826 (37%) and 3,156 (63%), respectively. Anti-HP antibody distribution per birth year revealed that earlier birth year was associated with higher HP+ rates. To remove confounding factors associated with birth year, a birth year-matched cohort (n = 3,376) was generated for subsequent analyses. All-cancer incidence was significantly higher in HP+ individuals than those who were HP- (p=0.00328), whereas there was no significant difference in the cancer death rate between HP+ and HP- individuals (p=0.888). Strikingly, we found that HP+ individuals who developed cancer had a better survival rate than would be expected based on cancer incidence. These results suggest that cancer patients who are HP+ may have a higher likelihood of survival than those who are HP-. Cox regression analysis for prognostic factors revealed that the hazards ratio of HP+ was 1.59-fold (95%CI 1.17-2.26) higher than HP- in all-cancer incidence.ConclusionsPotential systemic effects of HP+ status may contribute to reduced likelihood of death for patients with cancer.Data Availability StatementThe data cannot be shared publicly as data sharing is not permitted according to Japanese Government data protection policies. Requests for data analysis may be accepted anonymously and conditionally upon IRB approval from Iwate Medical University and Nagoya University Graduate School of Medicine.FundingThis study is supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (No. 17015018); Grants-in-Aid for Innovative Areas (No. 221S0001); and the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant (No. 19K09130 and No. 16H06277 [CoBiA]) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Competing interestsThe authors declare that no competing interests exist.Author summaryWhy was this study done?> Although HP infection is a major cause of gastric diseases including cancer, how HP infection affects prolonged survival of advanced gastric cancer patients is unknown.> Reports of studies carried out in different countries and regions revealed that advanced gastric cancer patients who are HP+ exhibited prolonged post-treatment survival, even though the genetic background of patients, HP strains, and cancer treatment procedures differed.> Since most advanced gastric cancer patients underwent gastrectomy, the favorable prognosis of HP+ patients after multidisciplinary treatment may be due to putative systematic mechanisms associated with HP infection.> If putative systemic mechanisms associated with HP infection reduce the likelihood of death due to cancer, the cancer survival rate in the HP+ population should be lower than that for the HP- population.What did the researchers do and find?> Using data from the DAIKO prospective cohort study in Nagoya, Japan, we analyzed the association between anti-HP antibody status, cumulative cancer incidence and all-cause and cancer-specific deaths.> The HP+ rate increased as birth year decreased. Thus, matching based on birth year between 1935 and 1975 was performed to correct for confounding factors associated with birth year.> Despite a significantly higher all-cancer incidence for HP+ individuals compared to those who were HP-, no difference in the all-cause and cancer death rate was observed between HP+ and HP- individuals.What do these findings mean?> HP+ individuals are less susceptible to death relative to their incidence of cancer.> Patients with advanced stage cancer who are HP+ may have a better treatment response/tolerance than those who are HP-.> Additional longitudinal analyses are warranted to evaluate the effect of HP+ status on prolonged survival of patients with advanced-stage cancer.

scholarly journals Down-regulation of HIF-1α inhibits the proliferation, migration, and invasion of gastric cancer by inhibiting PI3K/AKT pathway and VEGF expression

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jingjing Zhang ◽  
Jun Xu ◽  
Yonghong Dong ◽  
Bo Huang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Vegf Expression ◽  
Gastric Cancer Cells ◽  
Tumor Tissues ◽  
Sirna Silencing ◽  
Gastric Cancer Patients

In view of the high incidence of gastric cancer and the functions of hypoxia-inducible factor 1α (HIF-1α), our study aimed to investigate the functionality of HIF-1α in gastric cancer, and to explore the diagnostic and prognostic values of HIF-1α for this disease. Expression of HIF-1α in tumor tissues and adjacent healthy tissues as well as serum collected from both gastric cancer patients and normal healthy controls was detected by qRT-PCR. Survival analysis was performed using Kaplan–Meier method. HIF-1α siRNA silencing cell lines were established. Effects of HIF-1α siRNA silencing as well as PI3K activator sc3036 on proliferation, migration, and invasion of gastric cancer cells were detected by Cell counting kit (CCK-8) assay, and Transwell migration and invasion assay. Effects of HIF-1α siRNA silencing on AKT and VEGF were detected by Western blot. Expression of HIF-1α was significantly down-regulated in tumor tissues than in adjacent healthy tissues in most gastric cancer patients. Serum levels of HIF-1α were also higher in gastric cancer patients than in normal healthy people. Serum HIF-1α showed promising diagnostic and prognostic values for gastric cancer. HIF-1α siRNA silencing inhibited the proliferation, migration, and invasion of gastric cancer cells, while PI3K activator sc3036 treatment reduced those inhibitory effects. Down-regulation of HIF-1α can inhibit the proliferation, migration, and invasion of gastric cancer possibly by inhibiting PI3K/AKT pathway and VEGF expression.

ERCC1 mRNA expression and XRCC1 polymorphism as predictive factors for overall survival in gastric cancer patients receiving platinum based chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2512-2512 ◽  
Author(s):  
J. Wei ◽  
B. Liu ◽  
Z. Zou ◽  
X. Qian ◽  
W. Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Dna Repair ◽  
Survival Time ◽  
Cancer Patients ◽  
Predictive Factors ◽  
Median Survival Time ◽  
Platinum Based Chemotherapy ◽  
Ercc1 Expression ◽  
Gastric Cancer Patients

2512 Background: DNA repair was considered to play the key role in the platinum chemotherapy. ERCC1, XPD and XRCC1, three major components of the DNA repair pathway, are critical to outcome for patients treated with platinum based chemotherapy. Methods: Overall survival times in 48 stage III (47.9%) and IV (52.1%) gastric cancer patients were investigated. mRNA was isolated from formalin- fixed paraffin-embeded pretreatment primary tumor specimens and the relative expression of ERCC1 to the internal reference geneβ-actin was measured using real-time quantitative reverse transcriptase polymerase chain reaction. Two single nucleotide polymorphisms (SNPs) (XPD Lys751Gln and XRCC1 Arg399Gln) were also investigated using 5’ nuclease allelic discrimination assay (TaqMan). Results: Median age was 55 years (range: 23 to 75 years); 35 males and 13 females; median survival time was 397 days. The median ERCC1 gene expression level from all 48 gastric tumors was 1.16, and the cutoff values for chemotherapy was 0.30. The median survival time for patients with lower ERCC1 expression (31 of 48 patients) was 496 days, compared with 218 days for patients with higher ERCC1 expression (P < 0.0001). SNP of XRCC1 Arg399Gln was measured in 47 gastric cancer patients (97.92%). Median overall survival time was longer in patients with favorite allele G in codon 399 of XRCC1 (40 of 47 patients) than in others (respectively 420 days vs 218 days, P = 0.017). No significant relationship was found between SNP of XPD Lys751Gln and outcome of gastric cancer patients. Conclusions: These findings suggested that intratumoral ERCC1 mRNA expression and polymorphism of XRCC1 might be prominent predictive factors for overall survival of gastric cancer patients treated with platinum based chemotherapy. Multi-center clinical trial has been suggested. No significant financial relationships to disclose.

A phase II study to establish a referential arm for treatment of gastric cancer patients with intraperitoneal micrometastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15002-15002
Author(s):  
Y. Kodera ◽  
S. Ito ◽  
Y. Mochizuki ◽  
K. Kondo ◽  
N. Suzuki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Treatment Failure ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cytologic Examination ◽  
Time To Treatment ◽  
Time To Treatment Failure ◽  
Gastric Cancer Patients

15002 Background: Gastric cancer patients with free cancer cells in the peritoneal cavity as detected by cytologic examination of the peritoneal washes (CY1) are known to have dismal prognosis. In vivo studies by the authors suggest prognostic impact of early postoperative treatment with S-1 (Nakanishi H, et al. Cancer Sci 2003;94:112–8) . No standard treatment for this population has been proposed to date. Methods: A phase II study was conducted to evaluate the efficacy of S-1, a new oral fluoropyrimidine, given postoperatively to patients with CY1 disease. Eligibility criteria included histologically confirmed adenocarcinoma of the stomach without distant metastasis (peritoneal seeding allowed if completely resected), curatively resected with negative margins, <80 years of age with adequate organ functions and preoperative PS of 0∼2, and written informed consent. The primary endpoint was 2-year survival rate and secondary endpoints were time to treatment failure and safety. By referring to the historical control (2-year survival rate: 13.3%, 90% CI 3.1∼23.5%), the target 2- year survival rate was set at 36 % with estimated 90% CI>23.5%, and the sample size was calculated as 50. Results: Forty eight patients were accrued before the study was closed, and one patients was found to be ineligible (negative for the cytologic examination). Of 47 patients, 32 were men. Median age was 66 years (range: 39∼79 years). Serosal invasion was confirmed in 44 patients (94%) and node metastasis in 42 (89%). Seven patients had macroscopic but resectable peritoneal deposits. D2 dissection was encouraged and performed in 33 patients (70%). To date, median survival time was 21.7 months with 2-year survival rate of 43.5%. One patient died of ischemic heart disease 5 days after the initiation of treatment, and treatment for 7 other patients was discontinued due to toxicity. Time to treatment failure was 9.8 months and progression-free survival was 12.9 months. The most frequent >G3 toxicity was neutropenia (n=6), followed by anorexia/nausea (n=4). Conclusions: Although further period of observation is required, postoperative S-1 is likely to overwhelm the survival data obtained in the pre-S-1 era. Toxicity was manageable and 80% of the patients tolerated the treatment. No significant financial relationships to disclose.

Study to see the efficacy and toxicity profile of docetaxel-based chemotherapy in advanced stomach cancer in Bangladeshi patient population

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15687-e15687
Author(s):  
E. Hoque ◽  
S. Karim ◽  
M. Hossen ◽  
T. U. Ahmed
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Patient Population ◽  
Response Rate ◽  
Tumour Progression ◽  
Cancer Death ◽  
Toxicity Profile ◽  
Gastric Cancer Patients

e15687 Background: Gastric cancer is the second most common cause of cancer death worldwide. In Bangladesh it is one of the major causes of cancer death. Advanced gastric cancer patients have a poor prognosis of 3 to 5 months. Docetaxel has shown activity against gastric cancer as monotherapy and in combination with other agents. The purpose of this study was to investigate the efficacy and toxicity profile of docetaxel based chemotherapy in advanced stomach cancer in Bangladeshi patient population. Methods: From January 2004 to December 2006, thirty patients with advanced inoperable gastric cancer (Gastric or esophagogastric adenocarcinoma) were included in the study. Patients received no prior chemotherapy. Patients were given docetaxel 75mg/m2 I/V in 1 hour infusion and Cisplatin 75mg/m2 (d1) plus 5-fluorouracil 750mg/m2/d (days 1 to 5) I/V with adequate hydration every 3 weeks. The primary end point was time to tumour progression. Secondary end point was overall survival and toxicity profile. Results: Among the 30 evaluable patients time to tumour progression was 11.5 months. Overall response rate was 87% (26 patients). Complete response rate was 20% (6 patients), 27% (8 patients) had stable disease, 7% (2 patients) had developed progressive disease. Two-year survival rate was 21%. Grade 3 to 4 treatment related adverse events occurred in 63%. Among the toxicities there were: neutropenia (80%), stomatitis (19%), and diarrhea (15%). There was no treatment related death. Conclusions: Adding docetaxel to CF regimen significantly improved time to tumour progression and survival rate in advanced gastric cancer patients. In context with the survival benefit the toxicities of this regimen are acceptable. Docetaxel in combination with Cisplatin and 5-fluorouracil is a very safe and active in patients of Bangladesh with advanced gastric cancer. Larger studies involving higher number of patients are needed to evaluate these results in case of Bangladeshi patient population. No significant financial relationships to disclose.

Prognostic value of duodenal invasion length in patients with gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 24-24
Author(s):  
N. Oshima ◽  
M. Tokunaga ◽  
Y. Tanizawa ◽  
E. Bando ◽  
T. Kawamura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Cancer Patients ◽  
Curative Resection ◽  
R0 Resection ◽  
Resection Rate ◽  
Direct Invasion ◽  
Curative Operation ◽  
Duodenal Invasion ◽  
Gastric Cancer Patients

24 Background: Duodenal invasion (DI) has been considered as a poor prognostic factor of gastric cancer patients. Not all the patients would be able to undergo curative operation. Neoadjuvant chemotherapy (NAC) may improve the rate of curative operation of these patients. In this study, we investigated whether the length of duodenal invasion preoperative diagnosis can be one of factor to decide indication of NAC. Methods: A total of 118 gastric cancer patients with clinically evident DI, who underwent laparotomy at our center, were enrolled in this study. 42 patients with DI length 20 mm or longer were categorized into long invasion group (LI), 76 patients with DI length shorter than 20 mm were categorized into short invasion group (SI). Clinicopathologic features, rate of direct invasion and lymph nodes involvement, R0 resection, and survival rate were compared between two groups. Results: Resection rate was significantly different between two groups: SI group (85.5%; 65/76), LI group (69.0%; 29/42). Direct invasion to adjacent organs was significantly more frequently observed in LI group (21%; 6/29) than SI group (4 %; 3/65, p = 0.02). In LI group, pancreas invasion was observed in all patients except for one patient. Multivariate analysis to predict the adjacent organ invasion revealed that CT diagnosis (p = 0.005) and invasion length (p = 0.01) were selected as risk factors of direct invasion to adjacent organs. There was no significant difference of nodal involvement between LI group (83%; 24/29) and SI group (83%; 54/65 p = 0.99). The 5-year survival rate was 19% in LI group and 43% in SI group (p = 0.23). The number of patients who underwent R0 resection was more frequently in SI group (75.4%; 49/65) than SI group (69.1%; 16/29). The factors of R1 or R2 resection were metastasis of peritoneum or direct invasion to adjacent organs. Conclusions: In patients with long duodenal invasion, direct invasion to the pancreas was more frequently observed, and resulted in low curative resection rate and poor survival. Preoperative chemotherapy may improve the curative resection rate and survival in these patients. Prospective study is warranted to evaluate the efficacy of NAC for these patients. No significant financial relationships to disclose.

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