scholarly journals SATB1 enhances gastric cancer progression and metastasis via upregulation of CLIP4/DZIP1/ PRICKLE2 axis in gastric cancer patients

2021 ◽  
Vol 26 (6) ◽  
pp. 3062-3073
Author(s):  
SAMINA GUL ◽  
AMJAD ALI ◽  
SHAHZAD AHMAD ◽  
CHONGYI ZHAO ◽  
ASAD ALI SHAH ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Survival Rates ◽  
Signaling Axis ◽  
Satb1 Expression ◽  
Gastric Cancer Patients ◽  
Cancer Bioinformatics

SATB1 (Special AT-rich sequence binding protein 1) plays key role in chromatin remodeling and geneexpression. SATB1 has been shown to promote invasion, migration and metastasis. However, the underlying molecular mechanisms, function and clinicopathological features of SATB1 in gastric cancer (GC) remains poorly understood. Here, we show that SATB1 plays critical role in GC progression. SATB1 upregulates in GC patients’ samples and shows co-apmlification with a subset of oncogenic proteins (PRICKLE2, ZEB1, CBWX7, WWTR1, ENAH, DZIP1, IGSF11, ZSCAN18, GFRA2, GFRA1, FGFR1, HDAC4, GHR, TIMP3, CLIP4, TAGLN and ILK) in different subtypes of GC. SATB1 shows positive correlation with GC promoting oncogenes and enhances the expression of metastasis associated genes in GC samples to potentiate GC progression. SATB1 enhances WNT/NOTCH signaling axis in GC samples. In contrast, STAB1 suppresses a network of tumor suppressor genes in GC samples. Moreover, SATB1 expression negatively correlates with GC patient’s survival. Importantly, we found that SATB1 co-amplified genes CLIP4, DZIP1 and PRICKLE2 independently involve in GC progression. Overexpression of CLIP4, DZIP1 and PRICKLE2 show poor survival rates in GC patients. DZIP1 empowers AKT3/FGF2/FGFR1 and CXCR3/CXCR6 in GC patients. PRICKLE2 enhances GC progression by targeting FGFR1/NOTCH3/WNT4 signaling. Taken together, these results identified novel roles of SATB1, CLIP4, DZIP1 and PRICKLE2 in the GC invasion, migration and metastasis using cancer bioinformatics approach. These results highlights clinical significance of SATB1, CLIP4, DZIP1 and PRICKLE2 in GC patients and furthermore, these proteins may serve as prognostic markers in GC. These results also provide SATB1, CLIP4, DZIP1 and PRICKLE2 as potential chemotherapeutic targets in treatment of gastric cancer patients.

scholarly journals Prediction of cancer progression in a group of 73 gastric cancer patients by circulating cell-free DNA

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Wang-Yang Pu ◽  
Rong Zhang ◽  
Li Xiao ◽  
Yong-You Wu ◽  
Wei Gong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Cell Free Dna ◽  
Free Dna ◽  
Gastric Cancer Patients ◽  
Circulating Cell Free Dna

scholarly journals Pleckstrin-2 as a Prognostic Factor and Mediator of Gastric Cancer Progression

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jun Wang ◽  
Zhigang He ◽  
Bo Sun ◽  
Wenhai Huang ◽  
Jianbin Xiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
In Vivo Studies ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Gastric Cancer Patients

Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles of PLEK2 in gastric cancer are still unknown. PLEK2 expression in gastric cancer was examined by western blotting and real-time PCR. Survival analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. In vitro and in vivo studies were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways. PLEK2 expression was significantly upregulated in gastric cancer as compared with nontumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and proinvasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT through downregulating E-cadherin expression and upregulating Vimentin expression. Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may be a novel therapeutic target for gastric cancer.

scholarly journals Core 1–derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Fei Liu ◽  
Jianxin Fu ◽  
Kirk Bergstrom ◽  
Xindi Shan ◽  
J. Michael McDaniel ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Critical Role ◽  
Gastric Epithelium ◽  
Tn Antigen ◽  
Gastric Mucus ◽  
Truncated Form ◽  
Gastric Cancer Patients ◽  
Gastric Cancer Progression

Core 1–derived mucin-type O-glycans (O-glycans) are a major component of gastric mucus with an unclear role. To address this, we generated mice lacking gastric epithelial O-glycans (GEC C1galt1−/−). GEC C1galt1−/− mice exhibited spontaneous gastritis that progressed to adenocarcinoma with ∼80% penetrance by 1 yr. GEC C1galt1−/− gastric epithelium exhibited defective expression of a major mucus forming O-glycoprotein Muc5AC relative to WT controls, which was associated with impaired gastric acid homeostasis. Inflammation and tumorigenesis in GEC C1galt1−/− stomach were concurrent with activation of caspases 1 and 11 (Casp1/11)–dependent inflammasome. GEC C1galt1−/− mice genetically lacking Casp1/11 had reduced gastritis and gastric cancer progression. Notably, expression of Tn antigen, a truncated form of O-glycan, and CASP1 activation was associated with tumor progression in gastric cancer patients. These results reveal a critical role of O-glycosylation in gastric homeostasis and the protection of the gastric mucosa from Casp1-mediated gastric inflammation and cancer.

Docetaxel plus FOLFOX4 compared with FOLFOX4 as adjuvant chemotherapy for gastric cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 181-181
Author(s):  
Chun-Xia Du ◽  
Xiao-Yan Liu ◽  
Hong-Gang Zhang ◽  
Ai-Ping Zhou
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Survival Rates ◽  
Subtotal Gastrectomy ◽  
Disease Free Survival ◽  
Adjuvant Radiation ◽  
Ptnm Stage ◽  
Gastric Cancer Patients

181 Background: To compare the efficacy of docetaxel plus FOLFOX4 to FOLFOX4 as adjuvant chemotherapy for gastric cancer patients. Methods: 320 patients with stage IB-IV (M0) gastric cancer were enrolled into the retrospective study. All patients received a total or subtotal gastrectomy with at least D1 lymph nodes dissection. 193 patients received FOLFOX4 as adjuvant chemotherapy. 127 patients received biweekly docetaxel plus FOLFOX4 (DOF regimen) as adjuvant chemotherapy. Docetaxel was administered at 40 mg/m2 on day 1, followed by FOLFOX4 regimen. Both of the regimens were repeated every 2 weeks for a maximum of 12 cycles. Results: In comparison with patients in FOLFOX4 group, patients in DOF group were relatively younger (p=.001), with more advanced disease in pN stage (p=.035) and pTNM stage (p=.031), received more cycles of adjuvant chemotherapy (p=.004), and had a higher percentage of adjuvant radiation (p =.002). After adjustment of unbalanced variables as mentioned above, no statistical difference was observed between DOF group and FOLFOX4 group in terms of 3-year disease-free survival (54% vs 69%, p = 0.100, HR 1.362, 95% CI (0.943-1.967)) and 3-year overall survival(70% vs 72%, p = 0.810, HR 1.049, 95% CI (0.711-1.548)). Stratified analysis according to clinicopathologic characters showed that there were almost no statistical differences of 3-year overall survival rates between two groups, except the primary site (middle 1/3) (p =.025) and pTNM stage (IIb stage) (p =.035) in favor of FOLFOX4 group. The incidences of grade 3/4 adverse events were obviously higher in DOF group than in FOLFOX4 group,including decreased appetite (18.1% V 10.4%, P = 0.046), diarrhea (4.7% V 0%, p=0.004 ), hypersensitivity reactions to oxaliplatin (3.1% V 0%, p=0.024) and neutropenia (47.3% V 31.6%, p=0.004). Conclusions: Compared to FOLFOX4 regimen, adjuvant docetaxel plus FOLFOX4 did not show significant survival advantages in gastric cancer patients. However, a more serious toxicity profile was observed in docetaxel plus FOLFOX4 arm. Further studies are needed to decide whether triplet regimen is appropriate as adjuvant chemotherapy of gastric cancer.

scholarly journals Effect of Helicobacter Pylori on Plasma Metabolic Phenotype in Patients With Gastric Cancer

2021 ◽  
Vol 28 ◽  
pp. 107327482110418
Author(s):  
Yan-Ping Wang ◽  
Ting Wei ◽  
Xiao Ma ◽  
Xiao-Liang Zhu ◽  
Long-Fei Ren ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Early Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Acid Metabolism ◽  
Metabolic Phenotype ◽  
Multivariate Statistical ◽  
Gastric Cancer Patients

Background Although  Helicobacter pylori (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages. Purpose Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer. Results Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer. Conclusion This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.

scholarly journals Identifying Factors Affecting Cancer-related Death in Patients with Adenocarcinoma Gastric Cancer; An Analysis in the Presence of Competing Risks

2021 ◽  
Vol 14 (6) ◽  
Author(s):  
Malihe Safari ◽  
Hossein Mahjub ◽  
Habib Esmaeili ◽  
Mohamad Abasi ◽  
Ghodratollah Roshanaei
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Competing Risk ◽  
Risk Models ◽  
Subdistribution Hazard ◽  
Factors Affecting ◽  
Competing Risk Models ◽  
Gastric Cancer Patients

Background: Adenocarcinoma is the most common type of gastric cancer that has shorter survival than other types of gastric cancer. The death of patients with this type of cancer may be due to the progression of cancer or other related causes. Objectives: The aim of this study is to determine the factors affecting death due to the cancer progression in gastric cancer patients with the diagnosis of adenocarcinoma, using competing risk models. Methods: This retrospective cohort study was performed on 306 gastric cancer patients diagnosed with adenocarcinoma referring to Imam Khomeini clinic in Hamadan from 2002 to 2017. Death due to the cancer progression was considered an interest event and death due to without progression as a competing event. To determine the effect of covariates on hazard, the cause-specific and subdistribution hazard regression models were used. Data analysis was performed, using R3.6.1 software and cmprsk and survival packages. Results: The mean (SD) age of patients was 62.3 (12.5) years and 74.3% were male. The effect of the stage, the number of involved lymphomas, and the type of treatment were significant on the hazard of death due to the disease progression in both cause-specific and subdistribution hazard models. Conclusions: The results showed that most deaths occur in the first 3 years of follow-up. The higher stage and higher number of lymph nodes have increased the hazard of death but supplementary treatment significantly decreased the hazard of death due to cancer progression in adenocarcinoma gastric cancer patients in both competing risk models.

scholarly journals UFM1 suppresses invasive activities of gastric cancer cells by attenuating the expression of PDK1 through PI3K/AKT signaling

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Jian-Xian Lin ◽  
Xin-Sheng Xie ◽  
Xiong-Feng Weng ◽  
Sheng-Liang Qiu ◽  
Changhwan Yoon ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Invasion And Metastasis ◽  
Gastric Cancer Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Gastric Cancer Patients

Abstract Background UFM1 has been found to be involved in the regulation of tumor development. This study aims to clarify the role and potential molecular mechanisms of UFM1 in the invasion and metastasis of gastric cancer. Methods Expression of UFM1 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was analyzed by Western blotting, immunohistochemistry, and realtime PCR. Its correlation with the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. The effects of UFM1 on the invasion and migration of gastric cancer cells were determined by the wound and trans-well assays, and the effect of UFM1 on subcutaneous tumor formation was verified in nude mice. The potential downstream targets of UFM1 and related molecular mechanisms were clarified by the human protein kinase assay and co-immunoprecipitation technique. Results Compared with the corresponding adjacent tissues, the transcription level and protein expression level of UFM1 in gastric cancer tissues were significantly downregulated (P < 0.05). The 5-year survival rate of gastric cancer patients with low UFM1 expression was significantly lower than the patients with high UFM1 expression (42.1% vs 63.0%, P < 0.05). The invasion and migration abilities of gastric cancer cells with stable UFM1 overexpression were significantly decreased, and the gastric cancer cells with UFM1 stable knockdown showed the opposite results; similar results were also obtained in the nude mouse model. Further studies have revealed that UFM1 could increase the ubiquitination level of PDK1 and decrease the expression of PDK1 at protein level, thereby inhibiting the phosphorylation level of AKT at Ser473. Additionally, the effect of UFM1 on gastric cancer cell function is dependent on the expression of PDK1. The expression level of UFM1 can improve the poor prognosis of PDK1 in patients with gastric cancer. Conclusion UFM1 suppresses the invasion and metastasis of gastric cancer by increasing the ubiquitination of PDK1 through negatively regulating PI3K/AKT signaling.

scholarly journals Gastric cancer patients treated by a general or gastric cancer surgical team: a comparative study

2008 ◽  
Vol 45 (1) ◽  
pp. 28-33
Author(s):  
Fernando O. Souza ◽  
Dalnei V. Pereira ◽  
Luís H. Santos ◽  
Luis Antunes ◽  
Juarez Chiesa
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Survival Rates ◽  
University Hospital ◽  
Surgical Team ◽  
Pathologic Features ◽  
Number Of Patients ◽  
Group 2 ◽  
Gastric Cancer Patients ◽  
Group 1

BACKGROUND: Although gastric cancer has been decreasing in incidence in many countries, it is still the second most common cause of cancer deaths worldwide. Its prognosis is poor and depends, among other factors, on early diagnosis as well as on surgeon expertise. AIM: To compare the outcomes of gastric cancer patients treated at a university hospital by a general surgical team and later on by a gastric cancer surgical team. METHODS: Gastric cancer patients were separated into two groups according to whether they were treated by a general surgical team (group 1, n = 136; 1984 to 1993) or by gastric cancer team (group 2, n = 149; 1994 to 2003). Clinical and pathologic features and survival rates were assessed. RESULTS: During a 20-year period, a decreased number of patients underwent surgical resection in the second period (94% vs 86%), a greater number of upper gastrointestinal endoscopies were performed resulting in an increased number of tumors diagnosed as stage I (5% vs 22%). Also, D2 gastrectomies were more frequently performed instead of D0 gastrectomies and negative surgical margins were adequate. Mortality decreased from 9% to 6% in group 1 and 2, respectively and adjuvant therapy has been considered. CONCLUSION: Surgical specialized units for gastric cancer are necessary if better results are to be expected since this approach definitely provides better patient care.

scholarly journals Increased prevalence of precancerous changes in relatives of gastric cancer patients: Critical role of H. pylori

2000 ◽  
Vol 118 (1) ◽  
pp. 22-30 ◽  
Author(s):  
Emad M. El–Omar ◽  
Karin Oien ◽  
Lilian S. Murray ◽  
Adil El–Nujumi ◽  
Angela Wirz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Critical Role ◽  
H Pylori ◽  
Gastric Cancer Patients
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