Project description:A recent genome-wide association study identified seven single-nucleotide polymorphisms (SNPs) in region 16q24, near the Forkhead box-F1 (FOXF1) gene, which confer susceptibility to esophageal adenocarcinoma. We examined whether these SNPs are associated with clinical outcomes in gastric cancer (GC) patients in Japan and the United States. A total of 362 patients were included in this study: 151 Japanese GC patients treated with first-line S1 plus CDDP (training cohort) and 211 GC patients from Los Angeles County (LAC; validation cohort). Genomic DNA was isolated from whole blood or tumor tissue and analyzed by PCR-based direct DNA sequencing. Cox proportional hazard regression analyses were used to assess relationships between FOXF1 SNPs and progression-free survival (PFS) and overall survival (OS). FOXF1 rs3950627 was significantly associated with survival in both the training and validation cohorts. Japanese patients with the C/C genotype had a longer PFS (median 8.2 vs 5.3 months, hazard ratio (HR) 1.44, P=0.037) and OS (median 16.4 vs 12.2 months, HR 1.44, P=0.043) compared to patients with any A allele. Similarly, LAC patients with the C/C genotype had improved OS (3.9 vs 2.3 years, HR 1.5, P=0.022). Subgroup analyses showed these associations were specific to male patients and primary tumor subsite. Our findings suggest that FOXF1 rs3950627 might be a promising prognostic marker in GC patients.
Project description:Background: The Naples prognostic score (NPS) is established according to nutritional or inflammatory state, which has been identified as a new prognostic score for various malignant tumors. However, its prognosis prediction effect on gastric cancer (GC) patients is still unknown so far. The present work aimed to examine the NPS function in the prediction of GC prognosis. Methods: In this study, patients undergoing surgery with no preoperative therapy were retrospectively examined from June 2011 to August 2019. Typically, the total cholesterol level, serum albumin content, neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were determined to calculate the NPS. Besides, the prognostic value of NPS was evaluated by survival analyses. Time-dependent receiver operating characteristic (t-ROC) curve analysis was also carried out to compare the prognostic value of the scoring systems. Results: Altogether 1,283 cases were enrolled into the present work. NPS was markedly related to age, gender, tumor size, body mass index, vascular invasion, perineural invasion, and pTNM stage. Upon multivariate analysis, NPS was identified as an independent prognostic factor for the prediction of overall survival (OS) (P < 0.001). In subgroup analyses stratified by adjuvant chemotherapy or surgery alone, NPS was still the independent prognostic factor for OS in both groups (both P < 0.001). Furthermore, NPS exhibited higher accuracy in the prediction of OS than additional prognostic factors, as revealed by the results of t-ROC curve analysis. Conclusions: NPS is a simple and useful scoring system that can be used to independently predict the survival of GC cases undergoing surgery.
Project description:BackgroundInteractions of stromal hyaluronic acid (HA) with its binding protein RHAMM (receptor for HA-mediated motility) (CD168) have been reported to affect tumor extension and the migration of crucial molecules to promote tumor progression and metastases. Cancerous CD168 expression is correlated with aggressive biological features in several cancers. However, the clinical implications of CD168 positivity in gastric cancer have remained unclear.MethodsWe examined the CD168 expression of 196 consecutive gastric cancer patients by immunohistochemistry. According to CD168 positivity, the 196 gastric cancer patients were divided into two groups (57 CD168-positive and 139 CD168-negative patients). The correlation between CD168 expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status, and vessel invasion) was evaluated according to the Japanese Classification of Gastric Carcinoma.ResultsCancerous CD168 expression was detectable in 57 of the 196 tumors (29%). CD168 positivity was significantly correlated with the depth of invasion, nodal involvement, and vessel invasion (p < 0.01). Survival analysis of the 196 gastric cancer patients showed that the CD168-positive group had a significantly higher mortality than the CD168-negative group (p < 0.01). In terms of a correlation with CD168 positivity at separate clinical stages, a significance difference was only found in stages II and III. Multivariate analysis revealed that CD168 expression was a significant independent prognostic marker (p = 0.013) after depth of invasion (p < 0.005) and nodal involvement (p < 0.01).ConclusionOur results suggest that cancerous CD168 positivity is strongly related to the invasion and metastasis of gastric cancer tumors. These results suggest that cancerous CD168 expression can be used as a prognostic marker of gastric cancer owing to its interactions with stromal hyaluronic acid.
Project description:BackgroundFluorescent lymphography-guided lymphadenectomy (FL) for gastric cancer is gaining popularity. However, its impact on prognosis is not known. This study aimed to assess the prognostic impact of FL in gastric cancer patients.Materials and methodsThis study retrospectively analyzed 5678 gastric cancer patients who underwent gastrectomy from 2013 to 2017. The survival was compared between the FLFL group and the conventional lymphadenectomy (non-FL group) using 1:1 propensity score matching after exclusion. Patients in the FL group underwent gastrectomy with systematic lymphadenectomy after endoscopic peritumoral injection of indocyanine green the day before surgery.ResultsAfter propensity score matching, the FL and non-FL groups each had 1064 patients with similar demographic and clinicopathological characteristics. All matched variables had a standardized mean difference under 0.1. The FL group showed a significantly higher number of retrieved lymph nodes (56.2±20.1) than the non-FL group (46.2±18.2, P <0.001). The FL group also had more stage III patients ( P= 0.044) than the non-FL group. The FL group demonstrated higher overall survival ( P= 0.038) and relapse-free survival ( P= 0.036) in stage III compared with the non-FL group. However, no significant differences in overall and relapse-free survival were observed between the two groups for stages I ( P= 0.420 and P= 0.120, respectively) and II ( P= 0.200 and P= 0.280, respectively).ConclusionFL demonstrated a higher survival in stage III gastric cancer patients by the more accurate staging resulting from larger lymph node retrieval. Thus, given its potential to improve prognostication by enhancing staging accuracy, it is recommended as an option to consider the use of FL in clinical practice.
Project description:The role of NETosis and its related molecules remains unclear in gastric cancer. The data used in this study was directly downloaded from the Cancer Genome Atlas (TCGA) database. All analysis and plots are completed in R software using diverse R packages. In our study, we collected the list of NETosis-related genes from previous publications. Based on the list and expression profile of gastric cancer patients from the TCGA database, we identified the NETosis-related genes significantly correlated with patients survival. Then, CLEC6A, BST1 and TLR7 were identified through LASSO regression and multivariate Cox regression analysis for prognosis model construction. This prognosis model showed great predictive efficiency in both training and validation cohorts. We noticed that the high-risk patients might have a worse survival performance. Next, we explored the biological enrichment difference between high- and low-risk patients and found that many carcinogenic pathways were upregulated in the high-risk patients. Meanwhile, we investigated the genomic instability, mutation burden and immune microenvironment difference between high- and low-risk patients. Moreover, we noticed that low-risk patients were more sensitive to immunotherapy (85.95% vs. 56.22%). High-risk patients were more sensitive to some small molecules compounds like camptothecin_1003, cisplatin_1005, cytarabine_1006, nutlin-3a (-)_1047, gemcitabine_1190, WZ4003_1614, selumetinib_1736 and mitoxantrone_1810. In summary, our study comprehensively explored the role of NETosis-related genes in gastric cancer, which can provide direction for relevant studies.
Project description:To assess the impact of CD133 expression on the prognosis of endometrioid endometrial carcinoma (EEC). We retrospectively assessed CD133 expression in tissue microarray of 116 surgically treated FIGO I-III EEC. Tumors with ≥10% of CD133-expressing cells were considered CD133-positive (CD133+). On the basis of CD133 expression, clinical and pathological parameters, progression-free survival (PFS) and overall survival (OS) were evaluated. Of the EEC studied 85.2% showed CD133-expressing cells. Only 61% (n = 66) of EEC presented ≥10% of CD133 expressing cells and were considered CD133+. The mean OS for CD133+ tumour patients was 161 months (95% CI, 154-168) as compared with 146 months (95% CI, 123-160) for those with CD133- tumors (p = 0.012). The mean PFS for CD133+ tumour was 159 months (95% CI, 149-168) as compared with 147 months (95% CI, 132-161) in those with a CD133-tumour (p = 0.014). CD133+ tumours were less likely to have vascular invasion (p = 0.010) and more likely to be well differentiated (p = 0.034). C133+ tumours predicted favorable OS and PFS of EEC patients, with a Hazard Ratio 4.731 (95% CI, 1.251-17.89; p = 0.022). CD133+ tumor status correlates with favorable prognosis of EEC. Our findings are in agreement with studies addressing brain and colorectal tumours.
Project description:BACKGROUND: The inflammation-based Glasgow prognostic score (GPS) has been shown to be a prognostic factor for a variety of tumours. This study investigates the significance of the modified GPS (mGPS) for the prognosis of patients with gastric cancer. METHODS: The mGPS (0=C-reactive protein (CRP) ≤ 10 mg l(-1), 1=CRP>10 mg l(-1) and 2=CRP>10 mg l(-1) and albumin<35 g l(-1)) was calculated on the basis of preoperative data for 1710 patients with gastric cancer who underwent surgery between January 2000 and December 2007. Patients were given an mGPS of 0, 1 or 2. The prognostic significance was analysed by univariate and multivariate analyses. RESULTS: Increased mGPS was associated with male patient, old age, low body mass index, increased white cell count and neutrophils, elevated carcinoembryonic antigen and CA19-9 and advanced tumour stage. Kaplan-Meier analysis and log-rank test revealed that a higher mGPS predicted a higher risk of postoperative mortality in both relative early-stage (stage I; P<0.001) and advanced-stage cancer (stage II, III and IV; P<0.001). Multivariate analysis demonstrated the mGPS to be a risk factor for postoperative mortality (odds ratio 1.845; 95% confidence interval 1.184-2.875; P=0.007). CONCLUSION: The preoperative mGPS is a simple and useful prognostic factor for postoperative survival in patients with gastric cancer.
Project description:ObjectiveDysregulation of the c-MET signaling pathway results from various molecular mechanisms including mutation, amplification, and overexpression. Overexpression and amplification of c-MET have been correlated with poor clinical outcome in gastric cancer, whereas the associations between c-MET polymorphisms and prognosis have not been well defined. We examined the prognostic impact of functional polymorphisms of the MET gene on clinical outcome in gastric cancer.MethodsCandidate polymorphisms of the MET gene were analyzed by PCR-based direct sequencing for the associations with clinical outcome across three independent cohorts, including 161 Japanese, 101 US, and 63 Austrian patients, with locoregional gastric cancer, treated with surgery.ResultsThe univariable analysis showed that patients with any G (A/G or G/G genotype) allele of MET rs40239 had significantly longer disease-free survival and overall survival compared with those with the AA genotype in the Japanese cohort [hazard ratio (HR): 0.43, P=0.001, and HR: 0.47, P=0.006, respectively]; this remained significant upon multivariable analysis adjusted for age, sex, stage, and type of adjuvant therapy (HR: 0.48; P=0.009, HR: 0.50; P=0.017, respectively). However, there was no significant association of the polymorphism with clinical outcome in the US and Austrian cohorts. When stratified by sex in the Japanese cohort, male individuals, but not female individuals, with the G allele maintained a clinical outcome benefit in both univariable and multivariable analyses.ConclusionMET rs40239 may serve as a prognostic biomarker in locoregional gastric cancer. These data also suggest that genetic variants of c-MET may show sex-related differences in the impact on clinical outcome.
Project description:AimsThe aim was to describe the prevalence, characteristics, and outcome of patients with acute myocardial infarction (MI) developing left ventricular (LV) systolic dysfunction or pulmonary congestion by applying different criteria to define the population.Methods and resultsIn patients with MI included in the Swedish web-system for enhancement and development of evidence-based care in heart disease (SWEDEHEART) registry, four different sets of criteria were applied, creating four not mutually exclusive subsets of patients: patients with MI and ejection fraction (EF) < 50% and/or pulmonary congestion (subset 1); EF < 40% and/or pulmonary congestion (subset 2); EF < 40% and/or pulmonary congestion and at least one high-risk feature (subset 3, PARADISE-MI like); and EF < 50% and no diabetes mellitus (subset 4, DAPA-MI like). Subsets 1, 2, 3, and 4 constituted 31.6%, 15.0%, 12.8%, and 22.8% of all patients with MI (n = 87 177), respectively. The age and prevalence of different co-morbidities varied between subsets. For median age, 70 to 77, for diabetes mellitus, 22 to 33%; for chronic kidney disease, 22 to 38%, for prior MI, 17 to 21%, for atrial fibrillation, 7 to 14%, and for ST-elevations, 38 to 50%. The cumulative incidence of death or heart failure hospitalization at 3 years was 17.4% (95% CI: 17.1-17.7%) in all MIs; 26.9% (26.3-27.4%) in subset 1; 37.6% (36.7-38.5%) in subset 2; 41.8% (40.7-42.8%) in subset 3; and 22.6% (22.0-23.2%) in subset 4.ConclusionsDepending on the definition, LV systolic dysfunction or pulmonary congestion is present in 13-32% of all patients with MI and is associated with a two to three times higher risk of subsequent death or HF admission. There is a need to optimize management and improve outcomes for this high-risk population.