scholarly journals IL-6 and miR-1271 expression levels in elderly and young gastric cancer patients and correlation analysis with prognosis

Author(s):  
Shixiong Liu ◽  
Yun Zhou ◽  
Li Zhao ◽  
Jing Wang ◽  
Rui Ji ◽  
...  
2021 ◽  

Background: Gastric cancer (GC) is the most prevalent malignancy worldwide and a common cause of death in Iran. Studies have proved that a variety of dysregulated microRNAs is involved in the development and progression of gastric cancer. The present study aimed to evaluate the expression levels of plasma circulating oncogenic miR-21 and miR-192 and their association with clinical phenotypes of patients with gastric cancer in the north of Iran. Material and Methods: Clinico-pathological analysis was conducted using a standard protocol and pathological tests. The expression levels of miR-21 and miR-192 were measured using quantitative reverse transcription-polymerase chain reaction in the plasma of twenty pre/post-operative gastric cancer patients and twenty healthy subjects. The receiver operating characteristic (ROC) curve of these microRNAs was analyzed to investigate their diagnosis properties. Results: The study results indicated that plasma miR-21 expression was significantly associated with tumor stage and helicobacter pylori infection status (P=0.024, P=0.0004, respectively). However, no association was observed between clinic-pathological characteristics and miR-192 expression. The results showed that the plasma levels of miR-21 (P=0.0001) and miR-192 (P=0.0007) were significantly higher in GC patients compared to those in healthy individuals. Furthermore, the ROC analyses yielded the area under the curve (AUC) values of 0.9525±0.03 (P<0.0001) and 0.5925±0.09 (P=0.316) for miR-21and miR-192, respectively. Pearson regression analysis showed that there was no significant correlation between the expression of miR-21 and miR-192 (P=0.1507). Conclusion: Based on the obtained results, the expression of the plasma level of miR-21 was significantly higher in gastric cancer patients compared to that in the healthy group. Furthermore, the higher levels of AUC in miR-21 indicated the potential role of miR-21 as a noninvasive biomarker for the prognosis of gastric cancer in the population of the north of Iran.


2019 ◽  
Vol 34 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Yan Jin ◽  
Kun Zhou ◽  
Wenjing Zhao ◽  
Rongbo Han ◽  
Xinying Huo ◽  
...  

Background: The gene metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and an increasing amount of evidence suggests that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in gastric cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of positive MACC1 expression on clinicopathological features and survival outcomes in gastric cancer. Methods: Medline, Web of Science, and EMBASE databases were searched for relevant articles published up to 10 April 2018. The correlation of MACC1 expression levels with overall survival and clinicopathological features was analyzed. Results: In this meta-analysis, nine studies with a total of 2103 gastric cancer patients were included. Our results showed that high expression of MACC1 was significantly related to a poor overall survival. Moreover, our meta-analysis showed that MACC1 overexpression was significantly linked to distant metastasis and vascular invasion. There were no significant correlations between positive MACC1 expression and gender, localization, tumor-node-metastasis (TNM) stage, tumor extent (T stage) and lymph node involvement (N stage) Conclusions: MACC1 expression levels can serve as a novel prognostic factor in gastric cancer patients.


2021 ◽  
Author(s):  
Yi-Ling Chen ◽  
Chih-Yang Wang ◽  
Jung-Hua Fang ◽  
Hui-Ping Hsu

Abstract Background: Gastric cancer patients often present with distant metastasis and advanced stages. Suppressing serine/threonine-protein kinase 24 (STK24, also known as MST3) is known to promote gastric tumorigenesis. Here, we investigated the association between STK24 and the metastasis of gastric cancer.Methods: CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 technology was used for genetic knockout of STK24 at the genomic DNA level in human MKN45 and mouse M12 gastric cancer cells. To assess the effects of STK24 knockdown, western blot, cell migration, and wound healing assays were conducted in vitro. An in vivo mouse model of liver metastasis was established and tested, and bioinformatics analyses were performed.Results: The knockdown of the STK24 gene enhanced cell migration and increased liver metastasis in the mouse model of gastric cancer. STK24-silenced tumors suppressed CD4+ T cells and induced the expansion of CD11b+Ly6C+ myeloid-derived suppressor cells and F4/80+ macrophages in the spleen of the mice. In MKN45 cells, STK24 silencing resulted in downregulation of E-cadherin (CDH1, Cadherin-1, or epithelial cadherin). In 38 matched specimens of gastric adenocarcinomas and normal tissues, we examined STK24 and CDH1 expression levels via western blot; a significant positive correlation was found between the expression levels of STK24 and CDH1 (R2 = 0.5507, P = 9.72 × 10−8). Furthermore, in Oncomine database and Kaplan-Meier plotter analysis, the loss of CDH1, increase in CCL2, and upregulation of CD44 were correlated with poor prognosis in gastric cancer patients.Conclusions: Our results demonstrate that knockdown of STK24 increases cell migration and metastasis. STK24 suppression is also positively correlated with CDH1 expression in gastric cancer metastasis. Having developed an experimental metastatic model of gastric cancer in syngeneic inbred mice, we have shown that STK24 is important for immune regulation and regulates CDH1 expression during gastric metastasis.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Li ◽  
Jing Guo ◽  
Guang Cheng ◽  
Yucheng Wei ◽  
Shihai Liu ◽  
...  

BackgroundGastric cancer is one of the most common malignancies worldwide. Although the diagnosis and treatment of this disease have substantially improved in recent years, the five-year survival rate of gastric cancer is still low due to local recurrence and distant metastasis. An in-depth study of the molecular pathogenesis of gastric cancer and related prognostic markers will help improve the quality of life and prognosis of patients with this disease. The purpose of this study was to identify and verify key SNPs in genes with prognostic value for gastric cancer.MethodsSNP-related data from gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA) database, and the functions and pathways of the mutated genes were analyzed using DAVID software. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized by Cytoscape software, and molecular complex detection (MCODE) was used to screen the PPI network to extract important mutated genes. Ten hub genes were identified using cytoHubba, and the expression levels and the prognostic value of the central genes were determined by UALCAN and Kaplan-Meier Plotter. Finally, quantitative PCR and Western blotting were used to verify the expression of the hub genes in gastric cancer cells.ResultsFrom the database, 945 genes with mutations in more than 25 samples were identified. The PPI network had 360 nodes and 1616 edges. Finally, cytoHubba identified six key genes (TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4), and their expression levels were closely related to the survival rate of gastric cancer patients.ConclusionOur results indicate that TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4 may be key genes for the development and prognosis of gastric cancer. Our research provides an important bioinformatics foundation and related theoretical foundation for further exploring the molecular pathogenesis of gastric cancer and evaluating the prognosis of patients.


2021 ◽  
Author(s):  
Xuming Wang ◽  
Tian Liu ◽  
Lijuan Yu ◽  
Wenfa Mo ◽  
Longkuan Xu ◽  
...  

Abstract The present study aimed to investigate the clinicopathological features of EBV positive and EBV negative gastric cancer patients and the expression levels of proliferative, apoptotic and cell signaling proteins in tissues samples from these patients. The biological role of EBV infection was assessed in gastric cancer. Results: EBV was localized in the nuclei of gastric cancer cells (positive rate 6.86%). The infection rate of EBV in normal gastric mucosal cells, which were adjacent to cancer tissues, was 0. The difference noted was significant (P = 0. 023). The expression levels of caspase-3 (P = 0.0423), FASL (P = 0.00297) and cyclin D1 (P = 0.0345) proteins were significantly different in EBV positive and negative gastric cancer tissues. When the parameters gender, age, Lauren classification, histological grade, early and advanced tumor stage, vascular and nerve invasion, TNM grade and survival status were compared, the maximum tumor diameter, number of lymph node metastasis, caspase-8, Ki67 and P53 protein expression did not reveal significant differences. Bcl-2 protein expression was positive in only one gastric cancer cell sample and negative in the other gastric cancer cell samples as well as in the corresponding normal gastric mucosal epithelial cells. However, significant differences were noted with regard to the positive expression of Bcl-2 in the immune cells of gastric cancer and adjacent tissues (P = 1.17749E-39). The expression levels of Bcl-2 in the immune cells of EBV positive and EBV negative gastric cancer tissues were not significantly different. The expression levels of caspase-8, caspase-3, FASL, Ki67, cyclin D1 and P53 proteins in gastric cancer cells were significantly different compared to those of normal gastric mucosal cells derived from adjacent tissues (P < 0.05). These findings were noted in both EBV positive and/or EBV negative gastric cancer cases (P < 0.05). The survival time of the patients with EBV positive gastric cancer was higher than that of the patients with EBV negative gastric cancer, whereas the differences were not significantly different. The aforementioned results suggested that the EBV virus may directly infect cancerous cells but not normal gastric mucosal cells. With the exception of caspase-3, the expression levels of the proteins FASL and cyclin D1 were closely associated with EBV-positive gastric cancer. EBV did not have a specific effect on the expression of the signaling molecules associated with proliferation and apoptosis of gastric cancer cells. Its effect on gastric cancer cells may be associated with other factors and requires further discussion. No significant differences were noted in the clinicopathological features of EBV positive compared to those of EBV negative gastric cancer patients. However, the prognosis of EBV positive gastric cancer patients was better than that of EBV negative gastric cancer patients. The mechanism of action associated with these processes requires further verification.


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