scholarly journals Prognostic Value of Excision Repair Cross-Complementing mRNA Expression in Gastric Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-16
Author(s):  
Shan-Shan Luo ◽  
Xi-Wen Liao ◽  
Xiao-Dong Zhu

Except for excision repair cross-complementing 1 (ERCC1), mRNA expression of the remaining ERCC genes has not been investigated in the prognosis of gastric cancer (GC). The present study aimed to explore the mRNA expression and prognostic values of each member of the ERCC family in GC patients by using the Kaplan–Meier (KM) plotter tool. The details of each ERCC family member were entered into a database and GC patients were separated into high and low expression to draw survival plots using the KM plotter. In the present study, we observed that high expression of ERCC1 mRNA was significantly associated with longer overall survival (OS) for all GC patients (hazard ratio [HR]=0.77, 95% confidence intervals [CI]=0.63–0.95, P=0.016) compared with low expression. High expression of ERCC4 and ERCC6 mRNA indicated a worse OS for all GC patients (HR=1.28, 95% CI=1.02–1.6, P=0.035 and HR=1.25, 95% CI=1.02–1.54, P=0.029, respectively) and especially for patients with intestinal-type GC (HR=1.87, 95% CI=1.26–2.79, P=0.0018 and HR=1.62, 95% CI=1.04–2.54, P=0.033, respectively). High ERCC8 mRNA expression indicated a worse OS for all GC patients (HR=1.34, 95% CI=1.02–1.76, P=0.034) and especially for patients with diffuse-type GC (HR=2.25, 95% CI=1.36–3.75, P=0.0013). In conclusion, our findings indicate that ERCC4, ERCC6, and ERCC8 may be potential biomarkers for GC prognosis and may serve as potential therapeutic targets for GC. However, these findings still need further verification.

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Jun-Fu Wang ◽  
Ye Wang ◽  
Si-Wen Zhang ◽  
Ye-Yang Chen ◽  
Yue Qiu ◽  
...  

Background. Integrins are involved in the biological process of a variety of cancers, but their importance in the diagnosis and prognosis of gastric cancer (GC) is still unclear. Therefore, this study aimed at exploring the significance of ITG gene expression in GC to evaluate its diagnosis and prognosis. Methods. GEPIA data were used to evaluate the mRNA expression of ITG genes in GC patients. The prognostic value of these genes was assessed by analyzing their mRNA expression using the Kaplan–Meier curve. The biological function of ITG genes was evaluated by GC tissue sequencing combined with GSEA bioinformatics. Based on the sequencing data, ITGA5 with the largest expression difference was selected for verification, and RT-PCR was used to verify its mRNA expression level in 40 pairs of GC and normal tissues. Results. ITG (A2, A3, A4, A5, A6, A11, AE, AL, AM, AV, AX, B1, B2, B4, B5, B6, and B8) was highly expressed in GC tissues, while ITGA8 was low, compared with their expression in normal tissues. RNA-seq data shows that ITG (A2, A5, A11, AV, and B1) expression was associated with poor prognosis and overall survival. In addition, combined with the results of GC tissue mRNA sequencing, it was further found that the differentially expressed genes in the ITGs genes. ITGA5 was highly expressed in GC tissues compared with its expression in normal tissues, as evaluated by qRT–PCR ( P < 0.001 ) and ROC ( P < 0.001 , AUC (95% CI) = 0.747 (0.641–0.851)), and confirmed that ITGA5 expression was a potential diagnostic marker for GC. Bioinformatics analysis revealed that the signaling pathway involved in ITGA5 was mainly enriched in focal adhesion, ECM-receptor interaction, and PI3K-AKT and was mainly involved in biological processes such as cell adhesion, extracellular matrix, and cell migration. Conclusion. This study suggested that ITGs were associated with the diagnosis and prognosis of GC and discovered the prognostic value and biological role of ITGA5 in GC. Thus, ITGA5 might be used as a potential diagnostic marker for GC.


2020 ◽  
Author(s):  
Lili Wang ◽  
Hongguang Song ◽  
Shiming Yang

Abstract Background Oral cancer is a common malignant tumor in head and neck with poor prognosis. This study aimed to determine the expression tendency and prognostic value of PDGFRβ in oral cancer. Methods The mRNA expression level of PDGFRβ in the oral cancer tissues and adjacent normal tissues of oral cancer patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). And the association of PDGFRβ expression with clinicopathological characteristic was analyzed via chi-square test. Then we used Kaplan-Meier analysis to analyze the effects of PDGFRβ expression on the overall survival of oral cancer patients. The multivariate cox analysis was used to evaluate its prognostic value. Results The results indicated that the mRNA expression level of PDGFRβ was significantly increased in oral cancer tissues compared with that in the adjacent normal tissue ( P < 0.001). And its expression is positively associated with clinical stage, T stage, lymph node metastasis and histological grade. Kaplan-Meier analysis revealed that patients with high expression of PDGFRβ had markedly worse overall survival than those with low expression of PDGFRβ (log rank test, P < 0.05). Additionally, cox regression analysis revealed that the high expression of PDGFRβ was an independent prognostic maker in oral cancer patients. Conclusion PDGFRβ is up-regulated and involved in the development of oral cancer. Moreover, it could be an independent prognostic bio-marker for oral cancer.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maher Kurdi ◽  
Badrah Alghamdi ◽  
Nadeem Shafique Butt ◽  
Saleh Baeesa

Abstract Background Tumour associated macrophages (TAMs) and tumour infiltrating lymphocytes (TILs) are considered dominant cells in glioblastoma microenvironment. Aim The purpose of this study was to assess the expression of CD204+ M2-polarized TAMs in glioblastomas and their relationship with CD4+TILs, Iba+microglia, and IDH1 mutation. We also exploreed the prognostic value of these markers on the recurrence-free interval (RFI). Methods The expressions of CD204+TAMs, CD4+TILs, and Iba1+microglia were quantitively assessed in 45 glioblastomas using immunohistochemistry. Kaplan–Meier analysis and Cox hazards were used to examine the relationship between these factors. Results CD204+TAMs were highly expressed in 32 tumours (71%) and the remaining 13 tumours (29%) had reduced expression. CD4+TILs were highly expressed in 10 cases (22%) and 35 cases (77.8%) had low expression. There was an inverse correlation between CD204+TAMs and CD4+TILs, in which 85% of tumours had a high expression of CD204+TAMs and a low expression of CD4+TILs. Nevertheless, there was no significant difference in IDH1 mutation status between the two groups (p = 0.779). There was a significant difference in Iba1+microglial activation between IDH1mutant and IDH1wildtype groups (p = 0.031). For cases with a high expression of CD204+TAMs and a low expression of CD4+TILs, there was a significant difference in RFI after treatment with chemoradiotherapy or radiotherapy (p = 0.030). Conclusion Glioblastoma with a dense CD204+TAMs and few CD4+TILs is associated with IDH1wildtype. These findings suggest that TAMs masks tumour cell and suppress T-cell tumoricidal functions via immunomodulatory mechanisms. Blockade of the CD204-TAM receptor may prevent this mechanism and allow the evolution of TILs.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiao-fei Li ◽  
Hai-yan Sun ◽  
Tian Hua ◽  
Hai-bo Zhang ◽  
Yun-jie Tian ◽  
...  

Aberrant DNA methylation is considered to play a critical role in the chemoresistance of epithelial ovarian cancer (EOC). In this study, we explored the relationship between hypermethylation of the Mahogunin Ring Finger 1 (MGRN1) gene promoter and primary chemoresistance and clinical outcomes in high-grade serous ovarian cancer (HGSOC) patients. The MALDI-TOF mass spectrometry assays revealed a strong association between hypermethylation of the MGRN1 upstream region and platinum resistance in HGSOC patients. Spearman’s correlation analysis revealed a significantly negative connection between the methylation level of MGRN1 and its expression in HGSOC. In vitro analysis demonstrated that knockdown of MGRN1 reduced the sensitivity of cells to cisplatin and that expression of EGR1 was significantly decreased in SKOV3 cells with low levels of MGRN1 expression. Similarly, EGR1 mRNA expression was lower in platinum-resistant HGSOC patients and was positively correlated with MGRN1 mRNA expression. Kaplan-Meier analyses showed that high methylation of the MGRN1 promoter region and low expression of MGRN1 were associated with worse survival of HGSOC patients. In multivariable models, low MGRN1 expression was an independent factor predicting poor outcome. Furthermore, low expression of EGR1 was also been confirmed to be significantly related to the poor prognosis of HGSOC patients by Kaplan-Meier. The hypermethylation of the MGRN1 promoter region and low expression of MGRN1 were associated with platinum resistance and poor outcomes in HGSOC patients, probably by altering EGR1 expression.


2021 ◽  
Author(s):  
Juan Wang ◽  
Zihan Zheng ◽  
Qinghua Cao ◽  
Xiufen Liu ◽  
Zhiqing Wang

Abstract Backgroud Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. Methods In the present study, 2 datasets downloaded from the open Gene Expression Omnibus database were used to evaluate the mRNA level of OLA1 in gastric cancer. Quantitative Reverse Transcription PCR further validated the mRNA expression in gastric cancer tissues. Immunohistochemistry was performed on gastric cancer tissue microarray to assess OLA1 protein expression type, prognostic value, biological significance and its association with Snail in 334 patients of gastric cancer. The prognostic value of combination of OLA1 and Snail has been evaluated. Results The results showed that OLA1 mRNA and protein were elevated in gastric cancer tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumor size, lymph node metastasis and TNM stage (P = 0.0146, P = 0.0037, P < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (hazard ratio, 0.573; 95% confidence interval, 0.376–0.872; P = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and combination of them revealed improved prognostic accuracy for gastric cancer patients. Conclusions Our results suggested that OLA1 high expression was considered as an independent factor for the prediction of unfavorable prognosis in gastric cancer patients, and we believe that OLA1 could serve as a biomarker of poor prognosis and a novel target in treating gastric cancers.


2020 ◽  
Author(s):  
Sizhe Hu ◽  
Peipei Li ◽  
Chenying Wang ◽  
Xiyong Liu

Abstract Background: BGN (biglycan) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer.Material and Methods: Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets( n= 64, n=432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Bioinformatic analysis predicted the putative transcription factors of BGN.Results: For gastric cancer, the mRNA expression level of BGN in tumor tissues was significantly higher than that in normal tissues. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN significantly enriched metastasis and poor prognosis gene signatures, revealing that BGN might be associated with cell proliferation, poor differentiation, high invasiveness of gastric cancer. Meanwhile, the putative transcription factors, including AR, E2F1, and TCF4, weres predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.


2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Mingfu Tong ◽  
Wenquan Lu ◽  
Hao Liu ◽  
Jian Wu ◽  
Mingzuo Jiang ◽  
...  

Background. Metallothioneins (MTs) family comprises many isoforms, most of which are frequently dysregulated in a wide range of cancers. However, the expression pattern and exact role of each distinct MT family isoform which contributes to tumorigenesis, progression, and drug resistance of gastric cancer (GC) are still unclear. Methods. Publicly available databases including Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, SurvExpress, MethHC, cBioportal, and GeneMANIA were accessed to perform an integrated bioinformatic analysis and try to detect fundamental relationships between each MT family member and GC. Results. Bioinformatic data indicated that the mRNA expression of all MT family members was almost lowly expressed in GC compared with normal gastric tissue (P<0.05), and patients with reduced mRNA expression of each individual MT member had inconsistent prognostic value (OS, FP, PPS), which depended on the individual isoform of MT. A negative correlation between the methylation in promoter region of majority of MT members and their mRNA expression was detected from MethHC database (p<0.001). Data downloaded from TCGA revealed that MTs were rarely mutated in GC patients and MT2A was frequently regulated by other three genes (FOS, JUN, SP1) in GC patients. Conclusion. MTs were nearly downregulated, and distinct type of MT harbored different prognostic role in GC patients. Methylation in gene promoter region of MTs partially contributed to their reduced expression in GC. Our comprehensive analyses from multiple independent databases may further lead researches to explore MT-targeting reagents or potential diagnostic and prognostic markers for GC patients.


2018 ◽  
Vol 24 ◽  
pp. 2244-2251 ◽  
Author(s):  
Xin-Yang He ◽  
Jun Zhao ◽  
Zhi-Qiang Chen ◽  
Rong Jin ◽  
Cheng-Ye Liu

2015 ◽  
Vol 9 (4) ◽  
pp. 1393-1400 ◽  
Author(s):  
PENG SONG ◽  
QIN YIN ◽  
MING LU ◽  
BO FU ◽  
BAOLIN WANG ◽  
...  

2020 ◽  
Author(s):  
Sheng Li ◽  
Chao Yu ◽  
Yuanguang Cheng ◽  
Fangchao Du ◽  
Gang Wen

Abstract BackgroundGastric cancer (GC) is one of the most common malignancies in digestive system, among which the differentiation of diffuse type GC is relatively poor, the probability of distant metastasis and lymph node metastasis is relatively high, and the clinical prognosis is relatively poor. The purpose of this study is to explore potential signaling pathways and key biomarkers that drive the development of diffuse type GC. Methods Using the “limma” package in R to screen Differentially expressed genes. Screening hub genes by PPI analysis. Immunohistochemistry analysis and qRT-PCR analysis was carried out to detect genes expression. Using Kaplan-Meier Plotter database analyzed the prognostic roles of hub genes.ResultsA total of 355 DEGs consisting of 293 diffuse type DEGs and 62 intestinal type DEGs were selected according to screening criteria, 3 hub genes were chosen from diffuse type DEGs according to the degree of connectivity by using protein-protein interaction (PPI) networks and Cytoscape software including AGT, CXCL12 and ADRB2. Immunohistochemistry analysis and qRT-PCR results showed that the expression of three genes was related to the different GC lauren types. The Kaplan Meier analysis showed that the expression values of these three genes were related to prognosis of diffuse type GC. ConclusionsAGT, CXCL12 and ADRB2 might contribute to the progression of diffuse type GC, which could have potential as biomarkers or therapeutic targets for diffuse type GC.


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