Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.

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GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

Cancer Cell International ◽

10.1186/s12935-020-01692-z ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Hong Chen ◽

Lu Xu ◽

Zhi-li Shan ◽

Shu Chen ◽

Hao Hu

Keyword(s):

Gastric Cancer ◽

Transcription Factor ◽

Western Blot ◽

Wnt Signaling ◽

Cancer Cells ◽

Signaling Pathway ◽

Wnt Signaling Pathway ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Cancer Tissues

Abstract Background Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported. Methods Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot. Results The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes. Conclusions These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.

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LncRNA HCG11 promotes proliferation and migration in gastric cancer via targeting miR-1276/CTNNB1 and activating Wnt signaling pathway

Cancer Cell International ◽

10.1186/s12935-019-1046-0 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Hua Zhang ◽

Haitao Huang ◽

Xiaomei Xu ◽

Haiying Wang ◽

Jianxiang Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

Function Analysis ◽

Wnt Signaling Pathway ◽

Tumor Formation ◽

Tumor Promoter ◽

Luciferase Reporter ◽

And Migration ◽

Proliferation And Migration

Abstract Background Gastric cancer (GC) is one common cancer which occurs in the stomach leading to high mortality around the world. Long non-coding RNAs (lncRNAs) were found overexpressed or silenced in the occurrence and progression of multiple cancers including GC. Method The gene expression level in GC tissues and cells were analyzed by RT-qPCR. CCK-8, colony formation, flow cytometry and transwell assays were performed for the function analysis of HLA complex group 11 (HCG11). The mechanism study for HCG11 was conducted using RIP, RNA pull down and luciferase reporter assays. Results HCG11 was discovered highly expressed in GC tissues and cells. Depletion experiments were used to evaluate HCG11 silence on cell proliferation, migration and apoptosis. Moreover, Wnt signaling pathway was found as a tumor promoter in GC. RIP assay, RNA pull down assay and luciferase reporter assay were performed to illustrate the relationship of HCG11, miR-1276 and CTNNB1. Rescue assays revealed that HCG11/miR-1276/CTNNB1 axis regulated the incidence and development of GC. Tumor formation in mice proved that HCG11 was negatively correlated with miR-1276 and had positively correlation with CTNNB1. Conclusion Overall, HCG11 accelerated proliferation and migration in GC through miR-1276/CTNNB1 and Wnt signaling pathway, revealing that HCG11 could be a brand new target for GC.

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LINC00665 induces gastric cancer progression through activating Wnt signaling pathway

Journal of Cellular Biochemistry ◽

10.1002/jcb.29449 ◽

2019 ◽

Vol 121 (3) ◽

pp. 2268-2276 ◽

Cited By ~ 1

Author(s):

Bo Yang ◽

Qingqing Bai ◽

Huidong Chen ◽

Kun Su ◽

Chao Gao

Keyword(s):

Gastric Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

Cancer Progression ◽

Wnt Signaling Pathway ◽

Gastric Cancer Progression

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Sinomenine sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway

Anti-Cancer Drugs ◽

10.1097/cad.0000000000000834 ◽

2019 ◽

Vol 30 (10) ◽

pp. 983-990 ◽

Cited By ~ 7

Author(s):

Ying Liu ◽

Changqing Liu ◽

Ting Tan ◽

Shang Li ◽

Shunyu Tang ◽

...

Keyword(s):

Gastric Cancer ◽

Wnt Signaling ◽

Cancer Cells ◽

Signaling Pathway ◽

Wnt Signaling Pathway ◽

Negative Regulation ◽

Human Gastric Cancer ◽

Gastric Cancer Cells

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Long noncoding RNA FEZF1-AS1 indicates a poor prognosis of gastric cancer and promotes tumorigenesis via activation of Wnt signaling pathway

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2017.11.113 ◽

2017 ◽

Vol 96 ◽

pp. 1103-1108 ◽

Cited By ~ 40

Author(s):

Xiaoli Wu ◽

Peichen Zhang ◽

Hua Zhu ◽

Shi Li ◽

Xiangjian Chen ◽

...

Keyword(s):

Gastric Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Poor Prognosis ◽

Wnt Signaling Pathway

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The prognostic value of a tumor microenvironment-based immune cell infiltration score model in colon cancer

10.21203/rs.3.rs-496500/v1 ◽

2021 ◽

Author(s):

Xiaofen Pan ◽

Xingkui Tang ◽

Minling Liu ◽

Xijun Luo ◽

Mengyuan Zhu ◽

...

Keyword(s):

Colon Cancer ◽

Signaling Pathway ◽

Immune Cells ◽

Evaluation System ◽

Prognostic Value ◽

Immune Cell ◽

Wnt Signaling Pathway ◽

Mapk Signaling ◽

Cell Infiltration ◽

Immune Cell Infiltration

Abstract BackgroundTumor microenvironment consists of tumor cells, immune cells and other matric components. Tumor infiltration immune cells are associated with prognosis. But all the current prognosis evaluation system dose not take tumor immune cells other matrix component into consideration. In the current study, we aimed to construct a prognosis predictive model based on tumor microenvironment.MethodCIBERSORT and ESTIMATE algorithms were used to reveal the immune cell infiltration landscape of colon cancer. Patients were classified into three clusters by ConsensusClusterPlus algorithm. Immune cell infiltration (ICI) scores of each patient were determine by principal-component analysis. Patients were divided to high and low ICI score groups. Survival, gene expression and somatic mutation of the two groups were compared.ResultsPatients with no lymph node invasion, no metastasis, T1-2 disease and stage I-II had higher ICI scores. Calcium signaling pathway, leukocyte transendothelial migration pathway, MAPK signaling pathway, TGF β pathway, and WNT signaling pathway were enriched in high ICI score group. Immune-checkpoint genes and immune-activity associated genes were significantly decreased in high ICI score. Patients in high ICI score group had better survival than low ICI score group. Prognostic value of ICI score was independent of TMB.ConclusionICI score might serve as an independent prognostic biomarker in colon cancer.

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Prognostic value and biological significance of GUCY1A2 in gastric cancer: a bioinformatics analysis

10.21203/rs.3.rs-274107/v1 ◽

2021 ◽

Author(s):

Shan Huang ◽

Min Wei ◽

Mengyuan Zhu ◽

Xiaofen Pan

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Confidence Interval ◽

Calcium Signaling ◽

Signaling Pathway ◽

Prognostic Value ◽

Wnt Signaling Pathway ◽

Mapk Signaling ◽

Poor Survival ◽

Prognostic Predictor

Abstract Background: Guanylate cyclase 1 soluble subunit alpha 2 (sGCα2), also known as GUCY1A2, was reported to be upregulated and promoted tumorigenesis in some cancers. But whether GUCY1A2 was abnormally expressed and the prognostic value in gastric cancer was unknown. The current study aimed to find out the prognostic value of GUCY1A2 in gastric cancer by analyzing data from The Cancer Genome Atlas (TCGA). Methods: Wilcoxon signed-rank test, cox regression analysis and multivariant analysis were used to analyze the relationship between clinical characteristic and GUCY1A2 expression level. Kaplan-Meier method was used to analyze the association of GUCY1A2 and overall survival. Gene set enrichment analysis (GSEA) was used to identify GUCY1A2-related signaling pathway. Results: Compared to normal tissue, expression of GUCY1A2 was significantly increased in gastric cancer (p=0.000). Increased GUCY1A2 was associated with advance T stage (p=0.012) and poor survival (p=0.022). Univariate analysis showed that high GUCY1A2 expression was associated with a poor overall survival (HR:1.44, 95% confidence interval [CI]: 1.03-2.02, p=0.03). Multivariate analysis indicated that GUCY1A3 remained an independent prognostic predictor of overall survival (HR:1.75, 95% confidence interval [CI]: 1.20-2.56, p=0.00). GSEA revealed that calcium signaling pathway, MAPK signaling pathway, TGF-β signaling pathway and Wnt signaling pathway were enriched in GUCY1A2 high expression phenotype. Conclusions: GUCY1A2 maybe a potential prognostic predictor of poor survival in gastric cancer. Calcium signaling pathway, MAPK signaling pathway, TGF-β signaling pathway and Wnt signaling pathway may be the key signaling pathway regulated by GUCY1A2.

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The Prognostic Value of a Tumor Microenvironment-Based Immune Cell Infiltration Score Model in Colon Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.728842 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xingkui Tang ◽

Minling Liu ◽

Xijun Luo ◽

Mengyuan Zhu ◽

Shan Huang ◽

...

Keyword(s):

Colon Cancer ◽

Tumor Microenvironment ◽

Signaling Pathway ◽

Prognostic Value ◽

Immune Cell ◽

Wnt Signaling Pathway ◽

Mapk Signaling ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Score Model

The current study aimed to construct a prognostic predictive model based on tumor microenvironment. CIBERSORT and ESTIMATE algorithms were used to reveal the immune cell infiltration (ICI) landscape of colon cancer. Patients were classified into three clusters by ConsensusClusterPlus algorithm. ICI scores of each patient were determined by principal component analysis. Patients were divided into high and low ICI score groups. Survival, gene expression, and somatic mutation of the two groups were compared. We found that patients with no lymph node invasion, no metastasis, T1–2 disease, and stage I–II had higher ICI scores. Calcium signaling pathway, leukocyte transendothelial migration pathway, MAPK signaling pathway, TGF β pathway, and Wnt signaling pathway were enriched in the high ICI score group. Immune-checkpoint and immune-activity associated genes were decreased in high ICI score patients. Patients in the high ICI score group had better survival. Prognostic value of ICI score was independent of tumor mutational burden (TMB). The ICI score model constructed in the current study may serve as an independent prognostic biomarker in colon cancer.

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