Expression and Prognostic Analysis of Integrins in Gastric Cancer

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.

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Prognostic value of CLIC3 mRNA overexpression in bladder cancer

PeerJ ◽

10.7717/peerj.8348 ◽

2020 ◽

Vol 8 ◽

pp. e8348

Author(s):

Mei Chen ◽

Shufang Zhang ◽

Xiaohong Wen ◽

Hui Cao ◽

Yuanhui Gao

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Mrna Expression ◽

Prognostic Value ◽

Multivariate Analyses ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Receptor Interaction ◽

Normal Tissues

Background Human intracellular chloride channel 3 (CLIC3) is involved in the development of various cancers, but the expression and prognostic value of CLIC3 mRNA in bladder cancer (BC) remain unclear. Methods The gene expression data and clinical information of CLIC3 were obtained from the Gene Expression Omnibus (GEO) database and verified in the Oncomine and The Cancer Genome Atlas (TCGA) database. The expression of CLIC3 mRNA in BC tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The Kaplan-Meier method was used to analyze the relationship between the expression of CLIC3 mRNA and the prognosis of BC. Cox univariate and multivariate analyses were performed on the overall survival and tumor-specific survival of BC patients. The genes coexpressed with CLIC3 were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). CLIC3-related signal transduction pathways in BC were explored with gene set enrichment analysis (GSEA). Results The expression of CLIC3 mRNA in BC tissues was higher than that in normal tissues (P < 0.01). High CLIC3 mRNA expression was associated with age (P = 0.021) and grade (P = 0.045) in BC patients. High CLIC3 mRNA expression predicted a poor prognosis in BC patients (P < 0.05). Cox univariate and multivariate analyses showed that high CLIC3 mRNA expression was associated with tumor-specific survival in BC patients (P < 0.05). Functional enrichment analyses indicated that CLIC3 may be significantly associated with the cell cycle, focal adhesion, the extracellular matrix (ECM) receptor interaction and the P53 signaling pathway. Conclusions CLIC3 mRNA is highly expressed in BC, and its high expression is related to the adverse clinicopathological factors and prognosis of BC patients. CLIC3 can be used as a biomarker for the prognosis of BC patients.

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NUCKS1 Acts As A Promising Novel Bio-Marker in The Prognosis of Patients with Hepatocellular Carcinoma

10.21203/rs.3.rs-46795/v1 ◽

2020 ◽

Author(s):

Xianfeng Zhang ◽

Xianjun Zhang ◽

Xinguo Li ◽

Hongbing Bao ◽

Guang Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Mrna Expression ◽

Prognostic Value ◽

Cox Regression ◽

Rank Test ◽

Cox Regression Analysis ◽

Kinase Substrate ◽

Normal Tissues ◽

Kaplan Meier ◽

Relative Mrna Expression

Abstract Background: Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) was over-expressed in some tumors, including hepatocellular carcinoma (HCC). However, the clinical significance of NUCKS1 in HCC was still unclear. The aim of this study was to explore the expression and prognostic value of NUCKS1 in HCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of NUCKS1 in HCC tissues and corresponding adjacent normal tissues. The relationship between NUCKS1 expression and clinical characteristics of patients was analyzed by c2 test. Kaplan-Meier method and cox regression analysis were applied to estimate the prognostic value of NUCKS1 in HCC. Results: Compared with normal tissues, the relative mRNA expression level of NUCKS1 was significantly up-regulated in HCC tissues (P < 0.001). And high NUCKS1 expression was closely associated with tumor differentiation, TNM stage, vascular invasion and metastasis (P < 0.05). Kaplan-Meier analysis revealed that the overall survival of HCC patients with low expression of NUCKS1 was obviously longer than those with high NUCKS1 expression (log rank test, P = 0.001). NUCKS1 was an independent prognostic factor of HCC patients via univariate and multivariate cox regression analyses.Conclusions: NUCKS1 may be correlated with the progression of HCC and may serve as a potential factor for the prognosis of this disease.

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EFNA3 Can Serve as Potential Prognostic Biomarker for Luad Patients: A Comprehensive Analysis of the Eph/Ephrin Family

10.21203/rs.3.rs-105232/v1 ◽

2020 ◽

Author(s):

Gang Hou ◽

Mingming Deng ◽

Run Tong ◽

Zhe Zhang ◽

Tao Wang ◽

...

Keyword(s):

Prognostic Value ◽

Enrichment Analysis ◽

Progression Free Survival ◽

Synaptic Function ◽

Gene Set Enrichment Analysis ◽

Clinical Value ◽

Expression Levels ◽

Diagnosis And Prognosis ◽

Prognostic Analysis ◽

Kaplan Meier

Abstract Background: Ephrin receptors (Eph) and their ligands called ephrins, function in various disease processes. However, the specific mechanism of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear.Methods: Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. The Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Clinical LUAD tissue was analyzed by immunohistochemistry identifying the clinical value of identifying the ephrin-A3 protein. Weighted Co-expression Network Analysis (WGCNA) and Gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3.Results: EPHA10, EFNA3/4/5 and EPHB1/2 mRNA expression levels were significantly increased in LUAD. EFNB1/2 and EPHB6 expression levels were significantly decreased. Prognostic analysis showed that EFNA3, EFNB1/2, and EPHB2 expression were significant correlate with both overall survival (OS) and progression-free survival (PFS) in LUAD patients. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated as an independent risk prognosis factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. Additionally, higher expression of EFNA3 was significantly correlated with OS in pan-cancer patients.Conclusions: This study revealed the abnormal expression and prognostic value of Eph/Ephrin family members in LUAD. In addition, it is emphasized that EFNA3 may be a novel biomarker for the diagnosis and prognosis of LUAD patients.

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Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

Journal of Oncology ◽

10.1155/2020/9431560 ◽

2020 ◽

Vol 2020 ◽

pp. 1-24

Author(s):

Liang Liang ◽

Jin-hui Zhu ◽

Gang Chen ◽

Xin-gan Qin ◽

Jun-qiang Chen

Keyword(s):

Gastric Cancer ◽

Extracellular Matrix ◽

Mrna Expression ◽

Prognostic Value ◽

Kegg Pathway ◽

Meta Analysis ◽

Mrna Level ◽

Expression Levels ◽

Go Annotation ◽

Normal Tissues

The “A Disintegrin and Metalloproteinase with Thrombospondin Motif” (ADAMTS) family of genes is involved in the occurrence and development of different cancers. However, the prognostic value of these genes in gastric cancer (GC) has not been revealed. The present study was thus conducted to determine the prognostic value for the ADAMTS family of genes in GC. First, we evaluated the mRNA expression levels of the ADAMTS family in GC patients using a GEPIA dataset. Thereafter, we determined the prognostic value of these genes by analyzing their mRNA level using the Kaplan–Meier Plotter database. The mRNA expression level of ADAMTS12 was randomly validated by qRT-PCR and meta-analysis while its coexpression genes were derived using Coexpedia. Finally, we performed Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the OmicShare Tools. Compared to normal tissues, expression of ADAMTS2 and 12 was significantly higher while that of ADAMTS1, 13, and 15 was significantly lower in GC tissues. According to the RNA-seq and gene chip data, the ADAMTS family (6, 7, 12, 15, and 18) of genes was closely related to the prognosis of GC, and their high expression levels were associated with poor prognosis and survival time. In addition, ADAMTS12 was highly expressed in 20 pairs of GC tissues based on RT-PCR (P=0.016) and meta-analysis (SMD: 0.73, 95% CI: 0.32–1.14, P<0.001). GO and KEGG pathway analyses indicated that the ADAMTS12 coexpressed genes were enriched in the pathways of extracellular matrix organization, extracellular matrix structural constituent, extracellular matrix, and protein digestion and absorption. Herein, we discovered the prognostic values and biological roles of the ADAMTS genes in GC.

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

BioMed Research International ◽

10.1155/2018/6204684 ◽

2018 ◽

Vol 2018 ◽

pp. 1-16

Author(s):

Shan-Shan Luo ◽

Xi-Wen Liao ◽

Xiao-Dong Zhu

Keyword(s):

Gastric Cancer ◽

Mrna Expression ◽

Prognostic Value ◽

Excision Repair ◽

High Expression ◽

Diffuse Type ◽

Kaplan Meier ◽

Km Plotter ◽

Low Expression ◽

Potential Biomarkers

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.

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Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer

Cells ◽

10.3390/cells10071820 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1820

Author(s):

Chengcheng Hao ◽

Yuxin Cui ◽

Jane Lane ◽

Shuqin Jia ◽

Jiafu Ji ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Prognostic Value ◽

Splice Variants ◽

Tnm Staging ◽

Migration And Invasion ◽

Ros Production ◽

Gastric Cancer Cells ◽

Normal Tissues

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.

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Identification of Flap Endonuclease 1 With Diagnostic and Prognostic Value in Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.603114 ◽

2021 ◽

Vol 11 ◽

Author(s):

Min Wu ◽

Pan Zhang ◽

Penghui Wang ◽

Zhen Fang ◽

Yaqin Zhu

Keyword(s):

Breast Cancer ◽

Prognostic Marker ◽

Prognostic Value ◽

Diagnostic Value ◽

Roc Curve Analysis ◽

Free Survival ◽

Flap Endonuclease 1 ◽

Normal Tissues ◽

Kaplan Meier ◽

Kaplan Meier Plotter

ObjectiveThis study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).MethodsELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.ResultsBioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values>0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.ConclusionFEN1 might be a novel diagnostic and prognostic marker for BC.

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NaPi- II b as a potential diagnostic and prognostic biomarker in ovarian cancers

10.1101/394759 ◽

2018 ◽

Author(s):

Shoufeng Zhao ◽

Zhipeng Wang

Keyword(s):

Ovarian Cancer ◽

Cancer Cell Line ◽

Normal Tissues ◽

Diagnosis And Prognosis ◽

Kaplan Meier ◽

Potential Biomarker ◽

Tumor Types ◽

First Time ◽

Kaplan Meier Plotter ◽

Normal Controls

ABSTRACTOvarian cancer (OC) is commonly diagnosed at an advanced stage due to a lack of effective biomarkers and specificity required for accurate clinical diagnosis. The purpose of this study was to estimate the diagnosis and prognosis of the NaPi- II b in ovarian cancer. Herein, by performing data mining using the databases of Oncomine and Cancer Cell Line Encyclopedia (CCLE), we are for the first time to report that the expression level of NaPi- II b transcripts in a variety of tumor types compared with the normal controls. Based on Kaplan-Meier plotter, we investigated the prognostic values of NaPi- II b specifically high expressed in OC patients. The results of the Oncomine analysis showed that relative expression of NaPi- II b was distinctly high in OC tissues vs. normal tissues. CCLE analysis indicated that the expression of NaPi- II b in OC cell lines expressed the highest level in all cancer lines. In overall survival (OR) analysis, NaPi- II b mRNA high expressions were correlated to worse OR in OC patients. These results indicate that NaPi- II b may be a novel potential biomarker for determining the diagnosis and predicting the prognosis of OC.

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Evaluation of MT Family Isoforms as Potential Biomarker for Predicting Progression and Prognosis in Gastric Cancer

BioMed Research International ◽

10.1155/2019/2957821 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15

Author(s):

Mingfu Tong ◽

Wenquan Lu ◽

Hao Liu ◽

Jian Wu ◽

Mingzuo Jiang ◽

...

Keyword(s):

Gastric Cancer ◽

Mrna Expression ◽

Promoter Region ◽

Gene Promoter ◽

Distinct Type ◽

Bioinformatic Analysis ◽

Kaplan Meier ◽

Potential Biomarker ◽

Wide Range ◽

The Individual

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.

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Progressive and Prognostic Performance of an Extracellular Matrix-Receptor Interaction Signature in Gastric Cancer

Disease Markers ◽

10.1155/2020/8816070 ◽

2020 ◽

Vol 2020 ◽

pp. 1-23

Author(s):

Xiangchou Yang ◽

Liping Chen ◽

Yuting Mao ◽

Zijing Hu ◽

Muqing He

Keyword(s):

Gastric Cancer ◽

Extracellular Matrix ◽

Risk Score ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Receptor Interaction ◽

Clinicopathologic Features ◽

Normal Tissues ◽

Prognostic Application ◽

Score Model

The role of an extracellular matrix- (ECM-) receptor interaction signature has not been fully clarified in gastric cancer. This study performed comprehensive analyses on the differentially expressed ECM-related genes, clinicopathologic features, and prognostic application in gastric cancer. The differentially expressed genes between tumorous and matched normal tissues in The Cancer Genome Atlas (TCGA) and validation cohorts were identified by a paired t -test. Consensus clusters were built to find the correlation between clinicopathologic features and subclusters. Then, the least absolute shrinkage and selection operator (lasso) method was used to construct a risk score model. Correlation analyses were made to reveal the relation between risk score-stratified subgroups and clinicopathologic features or significant signatures. In TCGA (26 pairs) and validation cohort (134 pairs), 25 ECM-related genes were significantly highly expressed and 11 genes were downexpressed in gastric cancer. ECM-based subclusters were slightly related to clinicopathologic features. We constructed a risk score model = 0.081 ∗ log 2 CD 36 + 0.043 ∗ log 2 COL 5 A 2 + 0.001 ∗ log 2 ITGB 5 + 0.039 ∗ log 2 SDC 2 + 0.135 ∗ log 2 SV 2 B + 0.012 ∗ log 2 THBS 1 + 0.068 ∗ log 2 VTN + 0.023 ∗ log 2 VWF . The risk score model could well predict the outcome of patients with gastric cancer in both training ( n = 351 , HR: 1.807, 95% CI: 1.292-2.528, P = 0.00046 ) and validation ( n = 300 , HR: 1.866, 95% CI: 1.347-2.584, P = 0.00014 ) cohorts. Besides, risk score-based subgroups were associated with angiogenesis, cell adhesion molecules, complement and coagulation cascades, TGF-beta signaling, and mismatch repair-relevant signatures ( P < 0.0001 ). By univariate (1.845, 95% CI: 1.382-2.462, P < 0.001 ) and multivariate (1.756, 95% CI: 1.284-2.402, P < 0.001 ) analyses, we regarded the risk score as an independent risk factor in gastric cancer. Our findings revealed that ECM compositions became accomplices in the tumorigenesis, progression, and poor survival of gastric cancer.

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