scholarly journals Comprehensive Analysis of E2F Family Members in Human Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shengbo Li ◽  
Xiaofan Yang ◽  
Wenqing Li ◽  
Zhenbing Chen

Gastric cancer (GC) is the second most common cancer and the third most frequent cause of cancer-related deaths in China. E2Fs are a family of transcription factors reported to be involved in the tumor progression of various cancer types; however, the roles of individual E2Fs are still not known exactly in tumor progression of GC. In this study, we examined the expression of E2Fs to investigate their roles in tumor progression in GC patients using multiple databases, including ONCOMINE, GEPIA2, Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, GeneMANIA, STRING and UCSC Xena. We also performed real-time polymerase chain reaction (RT-PCR) to validate the expression levels of individual E2Fs in several GC cell lines. Our results demonstrated that the mRNA levels of E2F1/2/3/5/8 were significantly higher both in GC tissues and cell lines. The expression levels of E2F1 and E2F4 were correlated with poor overall survival (OS), decreased post-progression survival (PPS), and decreased progression-free survival (FP) in patients with GC. However, overexpression of E2F2, E2F5, E2F7 and E2F8 is significantly associated with disease-free survival and overall survival in patients with GC. In addition, higher E2F3 and E2F6 mRNA expression was found to increase GC patients’ OS and PPS. 224 of 415 patients with STAD (54%) had gene mutations that were associated with longer disease-free survival (DFS) but not OS. Cell cycle pathway was closely associated with mRNA level of more than half of E2Fs (E2F1/2/3/7/8). There were close and complicated interactions among E2F family members. Finally, our results indicated the gene expressions of E2Fs had a positive relationship with its copy numbers. Taken together, E2F1/2/3/5/8 can serve as biomarkers for GC patients with high prognostic value for OS of GC patients or therapeutic targets for GC.

2014 ◽  
Vol 31 (7) ◽  
Author(s):  
Xiao-tian Ye ◽  
Ai-jun Guo ◽  
Peng-fei Yin ◽  
Xian-dong Cao ◽  
Jia-cong Chang

2014 ◽  
Vol 21 (6) ◽  
pp. 1998-2004 ◽  
Author(s):  
Paolo Aurello ◽  
Simone Maria Tierno ◽  
Giammauro Berardi ◽  
Federico Tomassini ◽  
Paolo Magistri ◽  
...  

1999 ◽  
Vol 17 (12) ◽  
pp. 3810-3815 ◽  
Author(s):  
Lluís Cirera ◽  
Anna Balil ◽  
Eduard Batiste-Alentorn ◽  
Ignasi Tusquets ◽  
Teresa Cardona ◽  
...  

PURPOSE: The efficacy of adjuvant chemotherapy in gastric cancer is controversial. We conducted a phase III, randomized, multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer. PATIENTS AND METHODS: Patients with resected stage III gastric adenocarcinoma were randomly assigned, using sealed envelopes, to receive either chemotherapy or no further treatment. Chemotherapy was started within 28 days after surgery according to the following schedule: mitomycin 20 mg/m2 intravenously (bolus) at day 1 of chemotherapy; 30 days later, oral tegafur at 400 mg bid daily for 3 months. Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Between January 1988 and September 1994, 148 patients from 10 hospitals in Catalonia, Spain, were included in the study. The median follow-up period was 37 months. The tolerability of the treatment was excellent. The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy (P = .04 for survival and P = .01 for disease-free survival in the log-rank test). The overall 5-year survival rate and the 5-year disease-free survival rate were, respectively, 56% and 51% in the treatment group and 36% and 31% in the control group. CONCLUSION: Our positive results are consistent with the results of recent studies; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1616-1616 ◽  
Author(s):  
Eyal C. Attar ◽  
Kati Maharry ◽  
Krzysztof Mrózek ◽  
Michael D. Radmacher ◽  
Susan P. Whitman ◽  
...  

Abstract Abstract 1616 Poster Board I-642 CD74 is a type II integral membrane protein receptor that binds its ligand MIF to induce phosphorylation of the extracellular signal-regulated kinase-1/2 (ERK-1/2) and drive cellular proliferation via nuclear factor-kappa B (NF-kB) activation. CD74 expression has been identified in human solid tumors, and its expression is associated with adverse prognosis in advanced pancreatic cancer. As CD74 is expressed and NF-kB constitutively activated in myeloblasts, we hypothesized that CD74 expression might also be associated with adverse outcome in AML. To investigate the prognostic impact of CD74 expression in the context of other predictive molecular markers in CN-AML, we assessed CD74 expression levels by Affymetrix HG-U133 Plus 2.0 microarray in 102 younger [<60 years (y)] adults with primary CN-AML, treated on the front-line CALGB 19808 trial with an induction regimen containing daunorubicin, cytarabine, etoposide and, in some cases, the inhibitor of multidrug resistance valspodar, and consolidation with autologous stem cell transplantation. Microarray data were analyzed using the Robust Multichip Average method, making use of a GeneAnnot chip definition file, which resulted in a single probe-set measurement for CD74. At diagnosis, CD74 expression, when assessed as a continuous variable, was significantly associated only with extramedullary disease involvement (P=.006) among clinical features, and with none of the molecular prognostic variables tested, including NPM1, WT1, CEBPA, FLT3 (FLT3-ITD and FLT3-TKD) mutations, MLL partial tandem duplication, or differential BAALC and ERG expression levels. Although CD74 expression levels were not associated with achievement of complete remission (CR; 83% vs 81%), higher levels of CD74 were associated with shorter disease-free survival [DFS; P=.046, hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.12-3.08] and with shorter overall survival (OS; P=.02, HR 1.32, CI 1.04-1.67). In multivariable analyses, higher CD74 expression was independently associated with shorter DFS (P=.045, HR 1.98, CI 1.16-3.40), after adjusting for WT1 mutations (P<.001) and FLT3-TKD (P=.04), and shorter OS (P=.01, HR 1.58, CI 1.11-2.25) after adjusting for FLT3-TKD (P=.02), WT1 mutations (P=.007), BAALC expression levels (P=.02), white blood counts (P=.007), and extramedullary involvement (P=.04). As quartiles 2-4 had similar expression levels distinct from the lowest quartile, to display the impact of CD74 expression levels on clinical outcome only, pts were dichotomized into low (the lowest quartile) and high (the top three quartiles) CD74 expressers. The Kaplan-Meier curves for DFS and OS (Figures 1 and 2) are shown below. In conclusion, our study identifies elevated CD74 expression as associated with adverse prognosis in younger CN-AML pts. Since we previously reported that higher CD74 expression was favorably associated with achievement of CR in AML patients receiving chemotherapy plus bortezomib, an inhibitor of the proteasome and NF-kB (Attar et al., Clin Cancer Res, 2008;14:1446-54), it is possible that in future studies elevated CD74 levels can be used not only for prognostication, but also to stratify CN-AML pts to study of bortezomib-containing chemotherapy regimens. Figure 1 Disease free survival Figure 1. Disease free survival Figure 2 Overall survival Figure 2. Overall survival Disclosures No relevant conflicts of interest to declare.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 117-117
Author(s):  
Lin Chen ◽  
Kecheng Zhang ◽  
Zheng Peng ◽  
Bo Wei ◽  
Hongqing Xi ◽  
...  

117 Background: Autologous, tumor-derived heat shock protein Gp96 peptides complexes have shown antitumor potential in various cancers. We conducted the first Phase II trial to evaluate the safety and efficacy of Gp96 vaccination in adjuvant settings for patients with gastric cancer. Methods: Consecutive patients from November 2012 to December 2015 were enrolled. Participants were allocated to the experimental group or control group, receiving Gp96 vaccination plus chemotherapy or chemotherapy alone respectively. The primary endpoints were disease-free survival and toxicity. The secondary outcomes were overall survival and tumor-specific immune responses. Results: Thirty-nine and forty patients received Gp96 vaccination plus chemotherapy and chemotherapy alone in the adjuvant settings respectively. Significant increased tumor-specific immune responses were observed after Gp96 vaccination. There were comparable disease-free survival ( p = 0.413; HR: 0.75; 95% CI: 0.37−1.48) and overall survival ( p = 0.485; HR: 0.68; 95% CI: 0.24−1.96) between experimental group and control group. In subgroup of patients with stage II and stage III gastric cancer, patients who have received Gp96 vaccination had improved disease-free survival compared those who have not ( p = 0.044; HR: 0.45; 95% CI: 0.22−0.96). Gp96 vaccination plus chemotherapy was well tolerated and no Gp96-related serious adverse event has been observed. Conclusions: Gp96 vaccination could elicit tumor-specific immune responses and could be safely used in adjuvant settings combined with chemotherapy. Patients with less aggressive diseases might benefit from Gp96 therapy.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 311-311
Author(s):  
Beom Jin Kim ◽  
Eun Sun Lee ◽  
Joong-Min Park ◽  
In Gyu Hwang

311 Background: There is a lack of research on newly developed sarcopenia postoperatively. The purpose of this study was to investigate the risk factors and the clinical impact of postgastrectomy sarcopenia on the prognosis in patients undergoing radical gastrectomy for gastric cancer (GC). Methods: We retrospectively reviewed clinicopathological data from 430 consecutive GC patients who underwent surgical resection at Chung-Ang University Hospital between January 2011 and December 2015. Their skeletal muscle mass and abdominal fat volume were measured by abdominal CT imaging. Results: A total of 425 patients were analyzed in the study. The mean age was 62 years old and male were 301 (70.8%). Of these, 42 patients (9.9%) were diagnosed as pre-operative sarcopenia. Compared with non-sarcopenic group, pre-operative sarcopenia groups showed more female, higher BMI, less alcoholic, and less smoking. However, there was no significant difference in 5 - year overall survival and disease free survival between the groups (p = 0.836 and p = 0.638, respectively). Among 381 non-sarcopenic patients, 48 patients (12.6%) were diagnosed as newly developed sarcopenia in one year after gastric resection. Compared with non-sarcopenic group, the newly developed sarcopenic group showed more male, more undifferentiated tumor, lower hemoglobin level, less alcoholic, less smoking, and presence of diabetes mellitus. However, there was no significant difference in the 5 - year overall survival and disease free survival among non-sarcopenic, sarcopenic, and newly developed sarcopenic groups (p = 0.521 and p = 0.534, respectively). The relationship between preoperative body fat volume and postoperative muscle mass showed a significant correlation (rho = 0.296, p < 0.001), but only BMI was significantly associated with long term survival. Conclusions: Although newly developed sarcopenia after surgery did not affect the survival rate, patients with nutritional risk of sarcopenia after surgical resection may require early evaluation of nutritional status and nutritional support.


2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Nan Zhang ◽  
Peiyu Li ◽  
Xin Wu ◽  
Shaoyou Xia ◽  
Xudong Zhao ◽  
...  

Objective. Gastric cancer is a malignant tumor originating from gastric mucosal epithelium. Here, we aimed to investigate the analysis of the threshold change of gastric cancer tumor mutation burden (TMB) and its relationship with the prognosis of patients. Methods. 256 patients with gastric cancer were selected as subjects. All patients were in the advanced stage and received surgical resection of D2 lymph node dissection. After the operation, a follow-up was performed for 24 months, and the disease-free survival and overall survival of patients were counted. The NGS molecular biological was detected to obtain gastric cancer tumor mutation burden (TMB) data. Pearson correlation analysis software was used to analyze the correlation between TMB threshold and disease-free survival or overall survival of patients with gastric cancer, and the multivariate logistic analysis was performed as well. Results. The disease-free survival period and the overall survival period of patients in the low-to-medium TMB group were both longer than those in the high TMB group. Pearson correlation analysis results showed that the TMB threshold was negatively correlated with the disease-free survival and overall survival of gastric cancer patients. Results from multivariate logistic analysis showed that high TMB thresholds have a greater impact on disease-free survival and overall survival of patients, but the impact of medium and low TMB thresholds on disease-free survival and overall survival of patients is weakened. Conclusions. The TMB threshold level has a predictive effect on the effect of surgical resection of D2 lymph node dissection, and high levels of TMB can significantly affect disease-free survival and overall survival of patients with advanced gastric cancer.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4971
Author(s):  
Shion Wei Chai ◽  
Suo-Hsien Wang ◽  
Chih-Yuan Wang ◽  
Yi-Chan Chen ◽  
Ruey-Shyang Soong ◽  
...  

Background: Surgical treatment is the key to cure localized gastric cancer. There is no strong evidence that supports the value of omentectomy. Thus, a meta-analysis was conducted to compare the safety and efficiency of partial and total omentectomy in patients with gastric cancer. Methods: PubMed, Embase, and Cochrane Library databases were searched. All studies that compared total and partial omentectomy as treatments for gastric cancer were included. The primary outcomes were patients’ overall survival and disease-free survival, while the secondary outcomes were perioperative outcome and postoperative complications. Results: A total of nine studies were examined, wherein 1043 patients were included in the partial omentectomy group, and 1995 in the total omentectomy group. The partial omentectomy group was associated with better overall survival (hazard ratio: 0.80, 95% CI: 0.66 to 0.98, p = 0.04, I2 = 0%), shorter operative time, and lesser blood loss than the total omentectomy group. In addition, no statistically significant difference was observed in the number of dissected lymph nodes, length of hospital stays, complication rate, and disease-free survival. Conclusions: Our results show that, compared with total omentectomy in gastric cancer surgery, partial omentectomy had non-inferior oncological outcomes and comparable safety outcomes.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Xuling Liu ◽  
Hong Gao ◽  
Jie Zhang ◽  
Dongying Xue

AbstractPrognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P<0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005–2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III–IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.


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