scholarly journals Identification of F5 as a Prognostic Biomarker in Patients with Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Yi Liu ◽  
Xi-Wen Liao ◽  
Yu-Zhou Qin ◽  
Xian-Wei Mo ◽  
Shan-Shan Luo

Association of Coagulation factor V (F5) polymorphisms with the occurrence of many types of cancers has been widely reported, but whether it is of prognostic relevance in some cancers remain to be resolved. The RNA-sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA). The potential of F5 genes to predict the survival time of gastric cancer (GC) patients was investigated using univariate and multivariate survival analysis whereas “Kaplan-Meier plotter” (KM-plotter) online tools were employed to validate the outcomes. TCGA data revealed that F5 mRNA levels were significantly upregulated in gastric cancer samples. Survival analysis confirmed that high levels of F5 mRNA correlated with short overall survival (OS) in gastric cancer patients, and the area under the curve (AUC) values of 1-, 2-, and 5-year OS rate were 0.554, 0.593, and 0.603, respectively. Survival analysis by KM-plotter indicated that the high expression of F5 mRNA was significantly associated with a shorter OS compared with the low expression level in all patients with GC, and this was also the case for patients in stage III (hazard ratio HR=1.78, P=0.017). These findings suggest that the F5 gene is significantly upregulated in GC tumour tissues, and may be a potential prognostic biomarker for GC.

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Jun Li ◽  
Qingfeng Xu ◽  
Wen Wang ◽  
Shaojun Sun

Abstract The MIR100HG expression was observed to be up-regulated or down-regulated in human cancer tissues depending on tumor types. However, there was no report about the role of MIR100HG in gastric cancer. In our study, we first found levels of MIR100HG expression were increased in gastric cancer cell lines and tissue samples compared with normal gastric epithelial cell line and adjacent normal gastric mucosa tissue samples, respectively. Moreover, high MIR100HG expression was positively associated with clinical stage, tumor invasion, lymph node metastasis, and distant metastasis in gastric cancer patients. Survival analysis showed MIR100HG expression was negative correlated with clinical outcome in gastric cancer patients from The Cancer Genome Atlas (TCGA) database or our study, and high MIR100HG expression served as an independent poor prognostic factor for gastric cancer patient’s overall survival. The study in vitro suggested down-regulation of MIR100HG expression inhibits cell proliferation, migration, and invasion in gastric cancer. In conclusion, MIR100HG is a credible prognostic biomarker and functions as an oncogenic lncRNA in gastric cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jiayao Zhang ◽  
Xiaoyu Wang ◽  
Guangbing Li ◽  
Jingyi He ◽  
Ziwen Lu ◽  
...  

Purpose. This study is aimed at investigating the expression, underlying biological function, and clinical significance of coatomer protein complex subunit beta 2 (COPB2) in hepatocellular carcinoma (HCC). Methods. HCC-related data were extracted from The Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC) database, and Gene Expression Omnibus (GEO) database. A logistic regression module was applied to analyze the relationship between the expression of COPB2 and clinicopathologic characteristics. The Cox proportional hazard regression model and Kaplan–Meier method were used for survival analysis. Gene set enrichment analysis (GSEA) was used to annotate the underlying biological functions. Loss-of-function experiments were conducted to determine the underlying mechanisms. Results. COPB2 was overexpressed in HCC, and high expression of COPB2 was significantly correlated with higher alpha fetoprotein (AFP) (odds ratio OR = 1.616 , >20 vs. ≤20, p < 0.05 ), stage ( OR = 1.744 , III vs. I, p < 0.05 ), and grade ( OR = 1.746 , G4+G3 vs. G2+G1, p < 0.05 ). Kaplan–Meier survival analysis showed that HCC patients with high COPB2 expression had a worse prognosis than those with low COPB2 expression ( p < 0.0001 for TCGA cohort, p < 0.05 for ICGC cohort). The univariate Cox (hazard ratio HR = 1.068 , p < 0.0001 ) and multivariate Cox ( HR = 2.011 , p < 0.05 ) regression analyses suggested that COPB2 was an independent risk factor. GSEA showed that mTOR and other tumor-related signaling pathways were differentially enriched in the high COPB2 expression phenotype. Silencing of COPB2 inhibited the proliferation, migration, and invasion abilities by suppressing epithelial-mesenchymal transition and mTOR signaling. Conclusion. COPB2 is a novel prognostic biomarker and a promising therapeutic target for HCC.


2020 ◽  
Vol 7 ◽  
Author(s):  
Aizhai Xiang ◽  
Xia Lin ◽  
Lvping Xu ◽  
Honggang Chen ◽  
Jufeng Guo ◽  
...  

BackgroundThe exact biological role of PCOLCE was not yet clear and there were few reports study the correlation of PCOLCE gene expression level with the occurrence and development of gastric cancer.MethodsThe expression of PCOLCE was analyzed by performing the Oncomine and Ualcan database. We evaluated the function of PCOLCE on clinical prognosis with the use of Kaplan–Meier plotter database. The relationship between PCOLCE and cancer immune in filtrates was researched by Tumor Immune Estimation Resource (TIMER) site database.ResultsPCOLCE significantly upregulated in gastric cancer patients compared to normal gastric samples. And the increased expression of PCOLCE mRNA was closely linked to shorter overall survival (OS), progress-free survival (PFS) in all gastric cancers. Besides, PCOLCE expression displayed a tight correlation with infiltrating levels of macrophages and dendritic cells (DCs) in gastric cancer. Moreover, PCOLCE expression was positively correlated with diverse immune marker sets in gastric cancer.ConclusionAll the results above suggested that overexpression of PCOLCE indicated unfavorable prognosis in patients with gastric cancer. PCOLCE was correlated with immune infiltrating levels including those of B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and DCs in gastric cancer patients. All the findings suggested that PCOLCE could be used as a prognostic biomarker for determining prognosis and immune infiltration in gastric cancer. Additionally, PCOLCE expression potentially contributed to the regulation of monocyte, M2 macrophage, Tfh, CD8 + T cell, TAM, Th1 cell Thus PCOLCE is a potential target for gastric cancer therapy and these preliminary findings require further study to determine whether PCOLCE-targeting reagents might be developed for clinical application in gastric cancer.


Epigenomics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1251-1266
Author(s):  
Siheng Lin ◽  
Rui Zhou ◽  
Dongqiang Zeng ◽  
Jiani Wu ◽  
Jianhua Wu ◽  
...  

Aim: To develop novel diagnostic tools that can predict the prognosis of gastric cancer. Material & methods: Using RNA expression data from The Cancer Genome Atlas and Gene Expression Omnibus, we established protein-coding RNAs-noncoding RNAs-tumor microenvironment type (PNM) scores, which contain signatures of tumor protein coding genes (P), tumor noncoding genes (N) and immune/stroma cells in tumor microenvironment (M) to predict the prognosis of gastric cancer. Results & conclusion: Based on PNM scores, gastric cancer patients were divided into three subgroups and Kaplan–Meier survival curves revealed significant differences among the subgroups (p < 0.001). Our study showed that the PNM scores could be used as a robust predicting tool for the prognosis of gastric cancer.


2020 ◽  
Author(s):  
Chao Huang ◽  
Jiefeng Zhao ◽  
Zhikun Ning ◽  
Jun Huang ◽  
Zhengming Zhu

Abstract Background Self-renewal of gastric cancer stem cells (GCSCs) is considered to be the underlying cause of the metastasis, drug resistance and recurrence of gastric cancer (GC). The purpose of this study was to characterize the expression of stem cell-related genes in GC. Methods The RNA sequencing results and clinical data for gastric adenoma and adenocarcinoma samples were obtained from the Cancer Genome Atlas (TCGA) database, and the results of the GC mRNA expression-based stemness index (mRNAsi) were analyzed. Weighted gene coexpression network analysis (WGCNA) was then used to find modules of interest and their key genes. Survival analysis of key genes was performed using the online tool Kaplan-Meier Plotter, and the online database Oncomine was used to assess the expression of key genes in GC. Results mRNAsi was significantly upregulated in GC tissues compared to normal gastric tissues (p < 0.0001). A total of 16 modules were obtained from the gene coexpression network; the brown module was most positively correlated with mRNAsi. Sixteen key genes (BUB1, BUB1B, NCAPH, KIF14, RACGAP1, RAD54L, TPX2, KIF15, KIF18B, CENPF, TTK, KIF4A, SGOL2, PLK4, XRCC2 and C1orf112) were identified in the brown module. Survival analysis and Oncomine analysis revealed that the prognosis of patients with GC and the expression of three genes (RAD54L, TPX2 and XRCC2) were consistently related. Conclusion Sixteen key genes play an important role in the maintenance of GCSCs. RAD54L, TPX2 and XRCC2 are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.


Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 274 ◽  
Author(s):  
Xiangyan Wu ◽  
Dongfeng Qu ◽  
Nathaniel Weygant ◽  
Jun Peng ◽  
Courtney W. Houchen

Immunotherapy that has proven efficacy in several solid cancers plays a partial role in improving clinical outcomes of advanced gastrointestinal (GI) cancers. There is an unmet need to find new immune-related therapeutic targets. Doublecortin-like kinase 1 (DCLK1) marks tuft cells which are recognized as cancer-initiating cells and regulators of the type II immune response, and has been studied for its role in many cancers including colon and gastric cancers, but its role in tumor immunity remains unexplored. In the current study, we analyzed colon and gastric cancer RNA sequencing data from 283 and 415 patients, respectively, from The Cancer Genome Atlas (TCGA). High DCLK1 expression predicted the worse clinical outcomes in colon and gastric cancer patients and correlated with increased immune and stromal components. Further analysis indicated that DCLK1 was strongly linked to infiltration of multiple immune cell types, especially TAMs and Treg, and strongly correlated with increased CD8+ T cell inhibitors TGFB1 and CXCL12 and their receptors, suggesting it may contribute to TAM-mediated inhibition of CD8+ T cells. Interestingly, we found that DCLK1 was a prognostic biomarker in left-sided colon cancer, which has worse outcomes and demonstrates a reduced response to existing immunotherapies. In conclusion, our results demonstrate that DCLK1 is linked with functional regulation of the tumor microenvironment and may have potential as a prognostic biomarker and adjuvant target to promote immunotherapy sensitivity in colon and gastric cancer patients.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Tao Ran ◽  
ZhiJi Chen ◽  
LiWen Zhao ◽  
Wei Ran ◽  
JinYu Fan ◽  
...  

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengya He ◽  
Limin Yue ◽  
Haiyan Wang ◽  
Feiyan Yu ◽  
Mingyang Yu ◽  
...  

AbstractChromobox (CBX) proteins were suggested to exert epigenetic regulatory and transcriptionally repressing effects on target genes and might play key roles in the carcinogenesis of a variety of carcinomas. Nevertheless, the functions and prognostic significance of CBXs in gastric cancer (GC) remain unclear. The current study investigated the roles of CBXs in the prognosis of GC using the Oncomine, The Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, The Cancer Genome Atlas (TCGA), and cBioPortal databases. CBX1/2/3/4/5 were significantly upregulated in GC tissues compared with normal tissues, and CBX7 was downregulated. Multivariate analysis showed that high mRNA expression levels of CBX3/8 were independent prognostic factors for prolonged OS in GC patients. In addition, the genetic mutation rate of CBXs was 37% in GC patients, and genetic alterations in CBXs showed no association with OS or disease-free survival (DFS) in GC patients. These results indicated that CBX3/8 can be prognostic biomarkers for the survival of GC patients.


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.


2021 ◽  
pp. 153568
Author(s):  
Mingxia Jiang ◽  
Ling Qi ◽  
Kexin Jin ◽  
Lisha Li ◽  
Yiming Wu ◽  
...  

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