Expression and Clinical Significance of Serum Exosomal miR-375 in Patients with Gastric Cancer

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.

Author(s):  
Zilong Zhang ◽  
Linghong Zhu ◽  
Yanqing Ma ◽  
Bo Wang ◽  
Caihong Ci ◽  
...  

AbstractThe aim of this study is to compare and analyze the structure and diversity of intestinal flora between gastric cancer patients and healthy people in the Qinghai-Tibet Plateau and to explore the characteristics of the intestinal flora composition in gastric cancer patients in the plateau area, and to determine the possible correlation between the intestinal flora and gastric cancer. Fresh feces from 22 cases of gastric cancer patients diagnosed in a tertiary hospital in Qinghai Province and 30 cases of healthy people during the same period were collected. The 52 subjects were undergone for 16S rDNA gene sequencing of intestinal bacteria to analyze and compare the diversity and compositional characteristics of intestinal flora. Analysis of the diversity of intestinal flora between the gastric cancer group and the healthy group was based on the Chao1 index of species richness, Shannon diversity index, and Simpson index. It showed that the gastric cancer group had no statistically difference from the healthy group (P > 0.05). In the Venn diagram, the number of OTU units shared by the gastric cancer group and the healthy group is 6997, and the number of unique OTU units in the healthy group is 2282, while the number of OTU units in the gastric cancer group is 896 and the difference is statistically significant (χ2 = 495.829), P < 0.000). Analysis of the composition and abundance distribution of intestinal flora showed that at the phylum level, there is no significant deference in abundance between the healthy group of Bacteroides and Firmicutes compared with the gastric cancer group (P > 0.05). However, there is a statistically significant difference in abundance between the healthy groups of Proteobacteria compared with the gastric cancer group (P < 0.05). At the genus level, the gastric cancer group of Prevotella_9 is significantly different from the healthy group (P < 0.05). Meanwhile, the gastric cancer group of Streptococcus and Lactobacillus are significantly different from the healthy group (P < 0.001). There are differences in the composition and abundance of intestinal flora between patients with gastric cancer and healthy people in plateau areas, suggesting that Proteobacteria, Prevotella_9, Streptococcus, and Lactobacillus have increased in the Qinghai-Tibet Plateau and becoming one of the factors related to the incidence of gastric cancer in the region.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Guang-Chuan Mu ◽  
Yuan Huang ◽  
Zhi-Ming Liu ◽  
Xiang-Hua Wu ◽  
Xin-Gan Qin ◽  
...  

Abstract Background The aim of this study was to explore the prognostic factors and establish a nomogram to predict the long-term survival of gastric cancer patients. Methods The clinicopathological data of 421 gastric cancer patients, who were treated with radical D2 lymphadenectomy by the same surgical team between January 2009 and March 2017, were collected. The analysis of long-term survival was performed using Cox regression analysis. Based on the multivariate analysis results, a prognostic nomogram was formulated to predict the 5-year survival rate probability. Results In the present study, the total overall 3-year and 5-year survival rates were 58.7 and 45.8%, respectively. The results of the univariate Cox regression analysis revealed that tumor staging, tumor location, Borrmann type, the number of lymph nodes dissected, the number of lymph node metastases, positive lymph nodes ratio, lymphocyte count, serum albumin, CEA, CA153, CA199, BMI, tumor size, nerve invasion, and vascular invasion were prognostic factors for gastric cancer (all, P < 0.05). However, merely tumor staging, tumor location, positive lymph node ratio, CA199, BMI, tumor size, nerve invasion, and vascular invasion were independent risk factors, based on the results of the multivariate Cox regression analysis (all, P < 0.05). The nomogram based on eight independent prognostic factors revealed a well-degree of differentiation with a concordance index of 0.76 (95% CI: 0.72–0.79, P < 0.001), which was better than the AJCC-7 staging system (concordance index = 0.68). Conclusion The present study established a nomogram based on eight independent prognostic factors to predict long-term survival in gastric cancer patients. The nomogram would be beneficial for more accurately predicting the prognosis of gastric cancer, and provide important basis for making individualized treatment plans following surgery.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahui Pan ◽  
Xinyue Zhang ◽  
Xuedong Fang ◽  
Zhuoyuan Xin

BackgroundGastric cancer is one of the most serious gastrointestinal malignancies with bad prognosis. Ferroptosis is an iron-dependent form of programmed cell death, which may affect the prognosis of gastric cancer patients. Long non-coding RNAs (lncRNAs) can affect the prognosis of cancer through regulating the ferroptosis process, which could be potential overall survival (OS) prediction factors for gastric cancer.MethodsFerroptosis-related lncRNA expression profiles and the clinicopathological and OS information were collected from The Cancer Genome Atlas (TCGA) and the FerrDb database. The differentially expressed ferroptosis-related lncRNAs were screened with the DESeq2 method. Through co-expression analysis and functional annotation, we then identified the associations between ferroptosis-related lncRNAs and the OS rates for gastric cancer patients. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 17 ferroptosis-related lncRNAs. We also evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA).ResultsA ferroptosis-related “lncRNA–mRNA” co-expression network was constructed. Functional annotation revealed that the FOXO and HIF-1 signaling pathways were dysregulated, which might control the prognosis of gastric cancer patients. Then, a ferroptosis-related gastric cancer prognostic signature model including 17 lncRNAs was constructed. Based on the RiskScore calculated using this model, the patients were divided into a High-Risk group and a low-risk group. The K-M survival curve analysis revealed that the higher the RiskScore, the worse is the obtained prognosis. The ROC curve analysis showed that the area under the ROC curve (AUC) of our model is 0.751, which was better than those of other published models. The multivariate Cox regression analysis results showed that the lncRNA signature is an independent risk factor for the OS rates. Finally, using nomogram and DCA, we also observed a preferable clinical practicality potential for prognosis prediction of gastric cancer patients.ConclusionOur prognostic signature model based on 17 ferroptosis-related lncRNAs may improve the overall survival prediction in gastric cancer.


2021 ◽  
Author(s):  
Lei Xin ◽  
Fangrong Tang ◽  
Bo Song ◽  
Maozhou Yang ◽  
Jiandi Zhang

Background: One causing factor underlying failures of several clinical trials of anti-EGFR therapies is the lack of effective method to select patients overexpressing EGFR protein. Quantitative Dot Blot method (QDB) is proposed here to measure EGFR protein levels objectively and quantitatively. Its feasibility was evaluated for prognosis of overall survival (OS) of gastric cancer patients. Methods: FFPE slices of 2X5 microM from gastric and Lung cancer specimens were used to extract total tissue lysates for QDB measurement. Absolutely quantitated EGFR protein levels were used for Kaplan-Meier Overall Survival (OS) analysis of gastric cancer patients. Results: EGFR protein levels ranged from 0 to 772 pmole/g for gastric cancer specimens (n=246), and from 0 to 2695 pmole/g for lung cancer patients (n=81). Poor correlation was observed between quantitated EGFR levels and IHC scores with r=0.018, p=0.786 from Spearman correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric patients only through absolute quantitation, with HR at 2.29 (95%CI:1.23-4.26, p=0.0089) from multivariate cox regression OS analysis. A cutoff of 207.7 pmole/g was proposed to stratify gastric cancer patients, with 5-year survival probability at 37% for those whose EGFR levels were above the cutoff, and at 64% those below the cutoff based on Kaplan-Meier OS analysis. p=0.0057 from Log Rank test. Conclusion: A QDB-based assay was developed for both gastric and Lung cancer specimens to measure EGFR protein levels absolutely, quantitatively and objectively. This assay should facilitate clinical trials aiming to evaluate anti-EGFR therapies retrospectively and prospectively.


2017 ◽  
Vol 42 (5) ◽  
Author(s):  
Soykan Arikan ◽  
Alper Gümüş ◽  
Özlem Küçükhüseyin ◽  
Cihan Coşkun ◽  
Saime Turan ◽  
...  

AbstractObjective:Gastric cancer is one of the most common malignancies worldwide. The risk factors for gastric cancer include environmental and genetic factors. Inflammation and the immune system are known to contribute to the development of the gastric cancer. We examined the influence of critical polymorphisms of CTLA-4 and CD28 genes and circulating protein levels on the etiology of gastric cancer.Methods:Genotyping of SNPs was performed in 55 gastric cancer patients and 105 healthy individuals using the PCR-RFLP method, and circulating levels of sCTLA-4 and sCD28 were measured.Results:There were no significant differences in the genotype and allele distributions of the evaluated SNPs [CTLA-4-318 C>T (rs5742909), CTLA-4+49 A>G (rs231775), CD28 C>T (rs3116496)] between gastric cancer patients and controls (p=0.36, p=0.78, and p=0.80, respectively). The circulating levels of sCTLA-4 and sCD28 were significantly different between the gastric cancer group and the control group (p<0.001 and p<0.001, respectively).Conclusion:The present results suggest that the CTLA-4 and CD28 gene polymorphisms that were evaluated do not play an important role in Turkish patients with gastric cancer. However, sCTLA4 and sCD28 levels were higher in cancer patients and may be useful as an auxiliary parameter in the diagnosis and monitoring of gastric cancer.


2021 ◽  
Author(s):  
Jiarong Huang ◽  
Jinxuan Song ◽  
Xiangyu Li ◽  
Shuangfei Liu ◽  
Wentao Huang ◽  
...  

Abstract Background Studies have shown that long noncoding RNAs and N6-methyladenosine play an important role in gastric cancer. The purpose of this study was to determine the correlation and prognostic value of m6A-related lncRNAs and immune infiltration in gastric cancer. Methods We downloaded the clinically related information and RNA-Seq transcriptome data of gastric cancer patients from the TCGA database. Univariate Cox regression analysis and Pearson analysis were used to screen out m6A-related lncRNAs. Consensus cluster analysis was used to divide the sample into two clusters, and LASSO analysis and minimum absolute shrinkage were used to construct a risk scoring model. Results A total of 25 lncRNA expression profiles were screened, and gastric cancer patients were divided into different subtypes. Cluster 2 had a better prognosis, but its matrix score, estimate score and immune score were low. Cluster 1 was rich in resting memory CD4 T cells, regulatory T cells, monocytes, and resting mast cells, and Cluster 2 was rich in activated memory CD4 T cells and follicular helper T cells. Thirteen lncRNAs were selected to construct a risk model, and the prognosis of gastric cancer patients in the high-risk group was poor. The expression of PD-L1 in tumors is significantly higher than that in normal tissues. Univariate and multivariate Cox regression analysis results showed that the overall survival rate was significantly related to stage and risk score, which can be used as an independent prognostic factor. The results of the heat map and scatter plot showed that clusters (P=0.0045) and grade (G1-2, G3, P=0.0037) were significantly related to prognosis. The results of the relationship between the risk score and immune cell infiltration showed that memory B cells, resting dendritic cells, M0 macrophages, and M2 macrophages were positively correlated with risk scores, while resting mast cells, monocytes, activated NK cells, and follicular helper T cells were negatively correlated with risk scores. Conclusion The results of this study indicate that m6A-related lncRNAs may play an important role in the prognosis of gastric cancer patients and the tumor immune microenvironment and provide help for the treatment of gastric cancer patients.


2017 ◽  
Vol 32 (3) ◽  
pp. 278-283 ◽  
Author(s):  
Deng-Rui Liu ◽  
Quan-Lin Guan ◽  
Ming-Tai Gao ◽  
Lei Jiang ◽  
Hong-Xia Kang

Background The mannose receptor is an immune adhesion molecule mainly expressed on the surface of antigen-presenting cells such as nonmature dendritic cells and macrophages. This study aimed to investigate mannose receptor expression and its predictive role in papillary gastric cancer patients. Methods The expression of the mannose receptor was measured in 120 samples of gastric cancer tissues and corresponding paracarcinoma tissues, by immunohistochemical and quantitative real-time PCR analysis. The relationships between mannose receptor expression and clinicopathological features of gastric cancer patients were analyzed. Results The expression rate of the mannose receptor in gastric cancer cells was 45.8% (54/120), significantly higher than that in the paracarcinoma tissue (20.0%, 36/120) (χ2 = 6.286, p = 0.012). High expression of the mannose receptor was closely related to tumor size, T stage, N stage and Union for International Cancer Control (UICC) stage of gastric cancer (p<0.05). A Kaplan-Meier survival model indicated that the survival of patients in the high-expression mannose receptor group was significantly shorter than in the low-expression mannose receptor group (p<0.05). Cox regression analysis showed that high mannose receptor expression was an independent predictor for the prognosis of patients with gastric cancer. Conclusions High mannose receptor expression indicates poor prognosis for gastric cancer patients. The mannose receptor may be an important molecular marker for gastric cancer prognosis.


2020 ◽  
Vol 19 ◽  
pp. 153303382097167
Author(s):  
Tianqi Luo ◽  
Yufei Du ◽  
Jinling Duan ◽  
Chengcai Liang ◽  
Guoming Chen ◽  
...  

Gastric cancer is a malignant tumor with high morbidity and mortality worldwide. However, increasing evidences have revealed the correlation between the glycolysis process and tumorigenesis. This study is aim to develop a list of glycolysis-related genes for risk stratification in gastric cancer patients. We included 500 patients’ sample data from GSE62254 and GSE26942 datasets, and classified patients into training (n = 350) and testing sets (n = 150) at a ratio of 7: 3. Univariate and multivariate Cox regression analysis were performed to screen genes having prognostic value. Based on HALLMARK gene sets, we identified 9 glycolysis-related genes (BPNT1, DCN, FUT8, GMPPA, GPC3, LDHC, ME2, PLOD2, and UGP2). On the basis of risk score developed by the 9 genes, patients were classified into high- and low-risk groups. The survival analysis showed that the high-risk patients had a worse prognosis ( p < 0.001). Similar finding was observed in the testing cohort and 2 independent cohorts (GSE13861 and TCGA-STAD, all p < 0.001). The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for overall survival ( p < 0.001). Furthermore, we constructed a nomogram that integrated the risk score and tumor stage, age, and adjuvant chemotherapy. Through comparing the results of the receiver operating characteristic curves and decision curve analysis, we found that the nomogram had a superior predictive accuracy than conventional TNM staging system, suggesting that the risk score combined with other clinical factors (age, tumor stage, and adjuvant chemotherapy) can develop a robust prediction for survival and improve the individualized clinical decision making of the patient. In conclusion, we identified 9 glycolysis-related genes from hallmark glycolysis pathway. Based on the 9 genes, gastric cancer patients were separated into different risk groups related to survival.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Xue ◽  
Ming Ma ◽  
Songhua Bei ◽  
Fan Li ◽  
Chenqu Wu ◽  
...  

Immune checkpoint blockade has attracted a lot of attention in the treatment of human malignant tumors. We are trying to establish a prognostic model of gastric cancer (GC) based on the expression profile of immunoregulatory factor-related genes. Based on the TCGA database, we identified 234 differentially expressed immunoregulatory factors. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) conducted enrichment analysis to clarify the biological functions of differential expression of immunoregulatory factors. STRING database predicted the interaction network between 234 differently expressed immune regulatory factors. The expression of 11 immunoregulatory factors was significantly related to the overall survival of gastric cancer patients. Univariate Cox regression analysis, Kaplan–Meier analysis and multivariate Cox regression analysis found that immunomodulatory factors were involved in the progression of gastric cancer and promising biomarkers for predicting prognosis. Among them, CXCR4 was related to the low survival of GC patients and a key immunomodulatory factor in GC. Based on TCGA data, the high expression of CXCR4 in GC was positively correlated with the advanced stage and grade of gastric cancer and related to poor prognosis. Univariate analysis and multivariate analysis indicated that CXCR4 was an independent prognostic indicator for TCGA gastric cancer patients. In vitro functional studies had shown that CXCR4 promoted the proliferation, migration, and invasion of gastric cancer cells. In summary, this study has determined the prognostic value of 11 immunomodulatory factors in gastric cancer. CXCR4 is an independent prognostic indicator for gastric cancer patients, which may help to improve the individualized prognostic prediction of GC and provide candidates for the diagnosis and treatment of GC.


2020 ◽  
Author(s):  
Xin Xu ◽  
Chihao Zhang ◽  
Jun Zheng ◽  
Jiwei Yu

Abstract Background: The potential role of N6-methyladenosine (m6A) in cancer progression has received tremendous attention over the past few years. The aim of this study was to evaluate the effect of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) on the prognosis of patients and its potential role in gastric cancer.Methods: A total of 305 gastric cancer patients with clinical information were identified from the TCGA dataset. Limma package was used to analyze the differential m6A regulators; the Cox regression model was used to determine the risk factor for OS. A 1:1 propensity score matching (PSM) analysis was employed to adjust for the difference in baseline clinicopathological characteristics between the YTHDF2 low and high expression group. The Cox regression analysis was reused to identify the risk factors for overall survival (OS). GO and KEGG analysis were used to explore the potential role and function of YTHDF2 in gastric cancer.Results: Nineteen m6A methylation regulators were expressed in gastric cancer tissues; YTHDF2 was associated with the prognosis of gastric cancer patients. The expression level of YTHDF2, patient age, and tumor stage were independent risk factors for OS. After PSM, YTHDF2 expression led to a relatively better prognosis and stage. Patients in stage IV had a significantly poor prognosis. The expression of YTHDF2 was associated with cancer-related functions and pathways in gastric cancer.Conclusions: The high expression of YTHDF2 can predict a better prognosis of gastric cancer patients. YTHDF2 exerts a critical role in gastric cancer progression.


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