scholarly journals The roles of E2Fs in gastric cancer: the transcription factors E2F1/2/3/4/5 as potential therapeutic targets and E2F6/7/8 as new prognostic biomarkers in gastric cancer

2020 ◽  
Author(s):  
Hui Li ◽  
Shufen Zhao ◽  
Liwei Shen ◽  
Peige Wang ◽  
Shihai Liu ◽  
...  

Abstract Background E2F is a family of transcription factor proteins with multiple functions; E2F proteins are involved in cell cycle regulation, cell differentiation, the DNA damage response and cell death. Studies have shown that E2Fs have prognostic significance in many cancers, but the expression patterns and prognostic values of E2Fs in gastric cancer have not been systematically elucidated. Methods In this study, we used the ONCOMINE database and UALCAN online analysis website to compare the transcriptional levels and expression of eight E2F family members between gastric cancer and normal samples. UALCAN was also used to analyze the relationship between the expression of 8 E2F members and clinicopathological parameters. The prognostic value of the E2Fs were determined by Kaplan-Meier Plotter. A protein-protein interaction (PPI) network was constructed using the STRING database. The functions and pathways of E2F family and its neighboring 50 frequently changed genes were analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. Finally, quantitative PCR was used to verify the expression of E2Fs in gastric cancer cells. Results The expression patterns of 8 E2F members were significantly related to the clinical cancer stage and tumor grade of gastric cancer patients. High mRNA expression of E2F1/2/3/4/5 was a prognostic factor for poor OS in gastric cancer patients, while high expression of E2F6/7/8 was associated with better OS. In addition, a high mutation rate (46%) for E2Fs was observed in patients with gastric cancer. The expression levels of E2F1/2/3/5/8 in AGS and HGC27 cell lines were higher than those in normal cells, while E2F7 showed the opposite trend. Conclusions In summary, these results indicate that E2F1/2/3/4/5 can be used as potential therapeutic targets in gastric cancer, and E2F6/7/8 can be used as new prognostic markers to improve the survival rate and prognostic accuracy in gastric cancer.

2014 ◽  
Vol 29 (2) ◽  
pp. 99-111 ◽  
Author(s):  
Zhian Ling ◽  
Ruolin Li

Purposes For several years S100A4 has been implicated in tumor progression and prognosis. However, the prognostic value of S100A4 overexpression in patients with gastric cancer remains unknown. Therefore, we performed a meta-analysis to assess the relationship between S100A4 overexpression and clinical outcome of gastric cancer. Methods and Results Candidate studies were searched from PubMed, Embase, Cochrane Library, and ISI Web of Science. We included studies that evaluated the prognostic value of S100A4 expression in gastric cancer patients with regard to survival and a series of clinicopathological parameters. The pooled hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CI) were used to estimate the effects. Ten studies, all from Asia, were included in the meta-analysis. The pooled analysis showed that S100A4 overexpression was significantly associated with worse overall survival (OS) (HR=1.86, 95% CI: 1.45-2.38, p<0.00001) without heterogeneity in the data (I2=43.6%, p=0.131). Furthermore, our results showed that S100A4 overexpression was significantly correlated with some clinicopathological parameters such as tumor grade, stage, metastasis, invasion, and relapse. Conclusions The results of our meta-analysis indicate that S100A4 overexpression correlates with more adverse clinical features and a poor prognosis of gastric cancer patients in Asia, thus suggesting that S100A4 could be a useful marker to evaluate progression and prognosis of Asian gastric cancer patients. More studies from Western countries with a larger number of tumors and standardized methods are required before significant conclusions can be drawn.


2013 ◽  
Vol 31 (2) ◽  
pp. 605-612 ◽  
Author(s):  
TAKESHI IIDA ◽  
MAKOTO IWAHASHI ◽  
MASAHIRO KATSUDA ◽  
KOICHIRO ISHIDA ◽  
MIKIHITO NAKAMORI ◽  
...  

2010 ◽  
Vol 13 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Takeo Fukagawa ◽  
Mitsuru Sasako ◽  
Seiji Ito ◽  
Hayao Nakanishi ◽  
Hisae Iinuma ◽  
...  

2021 ◽  
Vol 7 (5) ◽  
pp. 3896-3904
Author(s):  
Daoting Deng ◽  
Hong Zhang ◽  
Junxi Liu ◽  
Lina Ma ◽  
Xinrui Lei ◽  
...  

To explore exosomal miR-375 expression in gastric cancer patients and its relationship with patient prognosis. A total of 53 patients diagnosed with gastric cancer in our hospital from May 2014 to May 2016 were included as the gastric cancer group, and 46 healthy women who came to our hospital for physical examination during the same period were enrolled as the healthy group. Exosomal miR-375 expression level was detected using qRT-PCR, and the diagnostic performance and prognostic significance of exosomal miR-375 in gastric cancer were explored. The gastric cancer group showed increased exosomal miR-375 expression than the healthy group (P< 0.05); Kaplan-Meier survival analysis exhibited that serum exosomal miR-375 has an AUC of 0.778, sensitivity of 69.57%, and specificity of 75.47%, whereas Cox regression analysis showed that the miR-375 expression in exosomes was an independent risk factor affecting the prognosis of gastric cancer patients (P< 0.05). Patient with gastric cancer showed upregulated miR-375 expression in serum exosomes. Serum exosomal miR-375 was found to has positive sensitivity and specificity in the diagnosis of gastric cancer, which may be associated with poor prognosis of gastric cancer patients.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Halon ◽  
Piotr Donizy ◽  
Przemyslaw Biecek ◽  
Julia Rudno-Rudzinska ◽  
Wojciech Kielan ◽  
...  

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4–12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P=0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patient’s age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC.


2009 ◽  
Vol 33 (11) ◽  
pp. 2378-2382 ◽  
Author(s):  
Naoto Fukuda ◽  
Yasuyuki Sugiyama ◽  
Akira Midorikawa ◽  
Hiroyuki Mushiake

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jingjing Zhang ◽  
Jun Xu ◽  
Yonghong Dong ◽  
Bo Huang

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.


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