Overexpression of RIPK4 Predicts Poor Prognosis and Promotes Metastasis in Ovarian Cancer

This study was conducted to evaluate the prognostic value of receptor-interacting protein kinase 4 (RIPK4) in ovarian cancer (OC) and its role in tumorigenesis. RNA expression and the corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The relationship between clinical-pathological characteristics and RIPK4 expression was analyzed using the Wilcoxon signed-rank test and logistic regression. The Cox regression and the Kaplan-Meier method were used to evaluate the relationship between clinicopathological features and overall survival (OS). Gene set enrichment analysis (GSEA) was performed using Molecular Signatures Database. Scratch assay, transwell assay, and cell transfection were used to verify the function of RIPK4. Overexpression of RIPK4 was associated with the stage of OC and distant metastasis. Survival analysis revealed that patients with OC and higher expression of RIPK4 had a poorer prognosis. Univariate and multivariate analyses indicated that high expression of RIPK4 was associated with poor OS, as well as age and stage of OC. The areas under the curve (AUC) at 1, 4, and 8 years were 0.737, 0.634, and 0.669, respectively, according to the established OS prediction model. GSEA revealed that adherens junction, cadherin binding, and Wnt signaling pathway were enriched in the high RIPK4 expression group. Cell transfection confirmed RIPK4 was involved in the Wnt signaling pathway. RIPK4 can act as a potential prognostic molecular marker for poor survival in OC. Moreover, RIPK4 is associated with tumor metastasis and implicated in the regulation of the Wnt signaling pathway.

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Wnt pathway-related three-mRNA clinical outcome signature in bladder urothelial carcinoma: computational biology and experimental analyses

Journal of Translational Medicine ◽

10.1186/s12967-021-03061-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Siqing Sun ◽

Yutao Wang ◽

Jianfeng Wang ◽

Jianbin Bi

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Wnt Pathway ◽

Cox Regression ◽

Wnt Signaling Pathway ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Immune Infiltration ◽

The Relationship

Abstract Background The Wnt signaling pathway is core to the growth of bladder tumors. Epithelial-to-mesenchymal transition (EMT) is significant for bladder tumor metastasis. Nevertheless, the relationship between the Wnt signaling pathway, outcomes of bladder cancer (BLCA), and the specific mechanisms driving immune infiltration have not been studied. Methods We obtained Wnt pathway-related gene mRNA and clinicopathological data from the Cancer Genome Atlas (TCGA). We obtained 34 genes that were greatly correlated with outcome using univariate Cox regression analysis and conducted a completely randomized data t-test to perform clinical staging. According to the single-sample gene set enrichment analysis (ssGSEA), the weighted correlation network analysis (WGCNA) was applied to identify relevant biological functions. Various subtypes were identified using consensus cluster analysis. Univariate Cox regression and least absolute shrinkage sum selection operator–Cox regression algorithm analysis were conducted on TCGA and Gene Expression Omnibus data to identify risk characteristics. The Kaplan–Meier method and receiver running feature curves were adopted to calculate overall survival. Single-sample gene set enrichment analysis (ssGSEA) was adopted for the assessment of the degree of immune infiltration. Then, we demonstrated the relationship between PPP2CB and EMT function in two cell lines. Results Thirty-four Wnt signaling pathway-related genes were risk factors for BLCA outcome, and their expression levels differed by clinical stage. The co-expression of WGCNA showed the relationship between the Wnt signaling pathway and biological functions and was closely associated with EMT. We divided BLCA patients into two subtypes using consensus clustering. Survival curves and clinical analysis showed that the Wnt pathway enriched group had worse outcomes. The Wnt signature showed the significance of the outcome for MAPK10, PPP2CB, and RAC3. Based on these genes, the degree of immune infiltration was evaluated. Cell function experiments suggested that PPP2CB drives the proliferation and migration of BLCA cells. Conclusion We found that Wnt signaling pathway-related genes can be used as prognostic risk factors for BLCA, and the Wnt signaling pathway is a cancer-promoting signaling pathway associated with EMT. We identified three critical genes: MAPK10, RAC3, and PPP2CB. The genes in these three Wnt signaling pathways are associated with tumor cell EMT and immune cell infiltration. The most important finding was that these three genes were independent prognostic factors for BLCA.

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Wnt Pathway-Related Three-mRNA Clinical Outcome Signature In Bladder Urothelial Carcinoma: Computational Biology And Experimental Analyses

10.21203/rs.3.rs-605515/v1 ◽

2021 ◽

Author(s):

Siqing Sun ◽

Yutao Wang ◽

Jianfeng Wang ◽

Jianbin Bi

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Wnt Pathway ◽

Cox Regression ◽

Wnt Signaling Pathway ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Immune Infiltration ◽

The Relationship

Abstract BackgroundThe Wnt signaling pathway is core to the growth of bladder tumors. Epithelial-to-mesenchymal transition (EMT) is significant for bladder tumor metastasis. Nevertheless, the relationship between the Wnt signaling pathway, outcomes of bladder cancer (BLCA), and the specific mechanisms driving immune infiltration have not been studied.MethodsWe obtained Wnt pathway-related gene mRNA and clinicopathological data from the Cancer Genome Atlas (TCGA). We obtained 34 genes that were greatly correlated with outcome using univariate Cox regression analysis and conducted a completely randomized data t-test to perform clinical staging. According to the single-sample gene set enrichment analysis (ssGSEA), the weighted correlation network analysis (WGCNA) was applied to identify relevant biological functions. Various subtypes were identified using consensus cluster analysis. Univariate Cox regression and least absolute shrinkage sum selection operator–Cox regression algorithm analysis were conducted on TCGA and Gene Expression Omnibus data to identify risk characteristics. The Kaplan–Meier method and receiver running feature curves were adopted to calculate overall survival. Single-sample gene set enrichment analysis (ssGSEA) was adopted for the assessment of the degree of immune infiltration. Then, we demonstrated the relationship between PPP2CB and EMT function in two cell lines. ResultsThirty-four Wnt signaling pathway-related genes were risk factors for BLCA outcome, and their expression levels differed by clinical stage. The co-expression of WGCNA showed the relationship between the Wnt signaling pathway and biological functions and was closely associated with EMT. We divided BLCA patients into two subtypes using consensus clustering. Survival curves and clinical analysis showed that the Wnt pathway enriched group had worse outcomes. The Wnt signature showed the significance of the outcome for MAPK10, PPP2CB, and RAC3. Based on these genes, the degree of immune infiltration was evaluated. Cell function experiments suggested that PPP2CB drives the proliferation and migration of BLCA cells.ConclusionWe found that Wnt signaling pathway-related genes can be used as prognostic risk factors for BLCA, and the Wnt signaling pathway is a cancer-promoting signaling pathway associated with EMT. We identified three critical genes: MAPK10, RAC3, and PPP2CB. The genes in these three Wnt signaling pathways are associated with tumor cell EMT and immune cell infiltration. The most important finding was that these three genes were independent prognostic factors for BLCA.

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LncRNA PAXIP1-AS1 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Ovarian Cancer

10.21203/rs.3.rs-1018252/v1 ◽

2021 ◽

Author(s):

Buze Chen ◽

Xiaoyuan Lu ◽

Qingmei Zhou ◽

Qing Chen ◽

Siyan Zhu ◽

...

Keyword(s):

Ovarian Cancer ◽

T Cells ◽

Signaling Pathway ◽

Clinical Characteristics ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

Th2 Cells ◽

Cox Regression Analysis ◽

Immune Infiltration ◽

The Relationship

Abstract Background: The long non-coding RNA (LncRNA) PAXIP1 antisense RNA 1 (PAXIP1-AS1) was found to promote proliferation, migration, EMT, and apoptosis of ovarian cancer (OC) cells in OC cell lines, but the relationship between PAXIP1-AS1 expression and clinical characteristics, prognosis, and immune infiltration of OC patients and its regulatory network are unclear. Methods: QRT-PCR, Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, Gene set enrichment analysis (GSEA), and immuno-infiltration analysis were used to evaluate the relationship between clinical characteristics and PAXIP1-AS1 expression, prognostic factors, and determine the significant involvement of PAXIP1-AS1 in function. Results: Low PAXIP1-AS1 expression in OC was associated with age (P=0.045), histological grade (P=0.011), and lymphatic invasion (P=0.004). Low PAXIP1-AS1 expression predicted a poorer overall survival (OS) (HR: 0.71; 95% CI: 0.55–0.92; P=0.009), progression free interval (PFS) (HR: 1.776; 95% CI: 1.067–2.955; P=0.001) and disease specific survival (DSS) (HR: 0.67; 95% CI: 0.51–0.89; P=0.006). And PAXIP1-AS1 expression (HR: 0.711; 95% CI: 0.542-0.934; P=0.014) was independently correlated with PFS in OC patients. GSEA demonstrated that neutrophil degranulation, signaling by Interleukins, GPCR-ligand binding, G alpha I signaling events, VEGFAVEGFR-2 signaling pathway, naba secreted factors, Class A 1 Rhodopsin-Like Receptors, PI3K-Akt signaling pathway, and Focal Adhesion-PI3K-Akt-mTOR-signaling pathway were differentially enriched in PAXIP1-AS1 high expression phenotype. PAXIP1-AS1 may inhibit the function of aDC, B cells, CD8 T cells, Cytotoxic cells, DC, iDC, Macrophages, Mast cells, Neutrophils, NK CD56dim cells, T cells, TFH, Tgd, Th1 cells, Th2 cells and Treg. Conclusions: Low expression of PAXIP1-AS1 was significantly associated with poor survival and immune infiltration in OC. PAXIP1-AS1 could be a promising prognosis biomarker for OC.

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Overexpression of MATN3 predicts poor prognosis of gastric adenocarcinoma: based on TCGA database

10.21203/rs.2.23505/v1 ◽

2020 ◽

Author(s):

GuoLiang Zheng ◽

Yan Zhao ◽

Zhichao Zheng

Keyword(s):

Signaling Pathway ◽

Gastric Adenocarcinoma ◽

Cox Regression ◽

Univariate Analysis ◽

Mtor Signaling ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Rank Test ◽

Mtor Signaling Pathway ◽

Kaplan Meier

Abstract Background Matrilin-3 (MATN3) was previously reported to in the cartilage extracellular matrix and had a role in the development and homeostasis of cartilage and bone. We evaluated the role of MATN3 in gastric adenocarcinoma (GAC) using publicly available data from The Cancer Genome Atlas (TCGA). Methods The relationship between clinicapathologic features and MATN3 were analyzed with the Wilcoxon signed-rank test and logistic regression. Clinicopathologic variables associated with overall survival (OS) in TCGA patients using Cox regression and the Kaplan-Meier method. Gene Set Enrichment Analysis (GSEA) was performed using TCGA cohort. Results MATN3 overexpressed in GAC than that in normal tissues (p﹤0.05), and MATN3 overexpression was significantly associated with TNM stage (p= 0.012), and T stage (p﹤0.01). Kaplan-Meier survival analysis showed that GAC with MATN3 - high had a worse prognosis than that with MATN3- low (p﹤0.01). The univariate analysis revealed that MATN3- high correlated significantly with a poor OS (HR: 1.86; 95% confidence interval [CI]: 0.82- 2.01; p = 0.014). The multivariate analysis revealed that MATN3 remained independently associated with OS, with a HR of 2.68 (CI: 0.74- 2.13; p﹤0.01). GSEA showed that NOTCH, WNT, and MTOR signaling pathway were differentially enriched in MANT3 high expression phenotype. Conclusion Overexpression of MATN3 may be a potential prognostic biomarker of poor survival in gastric cancer, Moreover, NOTCH, WNT, and MTOR signaling pathway may be the key pathway regulated by MATN3 in GAC.

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PSMC2 knockdown suppressed tumor progression of skin cutaneous melanoma

Cell Death Discovery ◽

10.1038/s41420-021-00727-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yanwen Yang ◽

Fazhi Qi ◽

Chuanyuan Wei ◽

Jiaqi Liu ◽

Yong Zhang ◽

...

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Cutaneous Melanoma ◽

Wnt Signaling Pathway ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Cycle Arrest ◽

Chip Technology ◽

Apoptosis Protein

AbstractSkin cutaneous melanoma (SKCM) is the most lethal tumor among three of the major malignant cancers of the skin. The mechanism underlying the malignant biological behaviors of SKCM is not fully clear. Our study intended to verify the molecular mechanism of proteasome 26 S subunit ATPase 2 (PSMC2) in malignant biological behaviors of SKCM. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of PSMC2 in SKCM and its impact on prognosis. PSMC2 expression in 105 paired SKCM tissues was investigated by immunohistochemistry (IHC), its functional roles were verified using a series of cell experiments, and the underlying pathway was detected by protein-chip technology and gene set enrichment analysis. We found that PSMC2 was significantly upregulated in SKCN patients from TCGA datasets and verified in clinical SKCM tissues. Moreover, high PSMC2 was shown to closely correlate with the pathological stages and lymphatic metastasis of SKCM patients. Functionally, knockdown of PSMC2 suppressed the progression of SKCM through inhibiting cell proliferation, migration, and DNA damage in vitro as well as cell growth in vivo, whereas inducing apoptosis, cycle arrest in G2 phase. Similarly, pharmaceutical inhibition of proteasome with MG132 mimicked the PSMC2 knockdown induced defects in cell cycle arrest, apoptosis and proliferation, while overexpression of PSMC2 has the opposite effects. Mechanistically, the silence of PSMC2 remarkably elevated the pro-apoptotic proteins DR6, IGFBP-4, p21, and p53, while inhibited the anti-apoptosis protein TRAILR-3 and the proteins related to the Wnt signaling pathway. The present study revealed that PSMC2 participated in a positive regulation to promote the progression of SKCM through regulating the Wnt signaling pathway. Our findings may offer a new mechanism underlying the development and progression of SKCM, and a deeper understanding of PSMC2 may contribute to SKCM treatment.

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GALNT14 expression in renal clear cell carcinoma and its effect on prognosis

10.21203/rs.3.rs-761157/v1 ◽

2021 ◽

Author(s):

Yuqin Wei ◽

Fan Wu ◽

Shengfeng Zhang ◽

Yanlin Tan ◽

Qunying Wu ◽

...

Keyword(s):

Cell Carcinoma ◽

Cox Regression ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Regulatory Pathways ◽

Cox Analysis ◽

The Relationship

Abstract Background The expression of GALNT14 in kidney renal clear cell carcinoma (KIRC) and its clinical significance remains unknown. Methods The KIRC data expressed by GALNT14 was downloaded from The Cancer Genome Atlas (TCGA) database. The expression of GALNT14 was analyzed by R software, Perl software and online analysis database. The relationship between GALNT14 expression and clinicopathological features in KIRC was analyzed by univariate, multivariate Cox regression and some databases. Gene Expression Profling Interactive Analysis (GEPIA), Starbase v3.0, UALCAN, and Kaplan-Meier were used to analyze the relationship between GALNT14 expression and overall survival (OS) in KIRC. UALCAN detects the expression of GALNT14 methylation in KIRC. Linkedomics and Genemania were used to analyze the gene co-expression of GALNT14. Gene Set Enrichment Analysis (GSEA) was performed to search for potential regulatory pathways. Results We found that GALNT14 was overexpressed in KIRC (p=1.433e-25). Patients with high GALNT14 expression in KIRC had a better prognosis than patients with low GALNT14 expression (p=0.008). In addition, high GALNT14 expression in KIRC was significantly associated with low T stage and positive OS (p<0.05). Univariate Cox analysis showed that GALNT14 was positively correlated with OS (p<0.001). Multivariate Cox analysis showed that GALNT14 was associated with OS (p<0.001), age (p=0.01) and histological grade (p=0.02). GALNT14 methylation is low expressed in KIRC (p<0.001). GSEA analysis showed that GALNT14 was enriched in histidine metabolism, peroxisome, and renin-angiotensin system pathways. Conclusion GALNT14 can be used as an independent prognostic factor for renal clear cell carcinoma and a potential target for clinical diagnosis and treatment of KIRC.

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Clinical Value of lncRNA LUCAT1 Expression in Liver Cancer and its Potential Pathways

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld-356 ◽

2019 ◽

Vol 28 (4) ◽

pp. 439-447 ◽

Cited By ~ 7

Author(s):

Yan Jiao ◽

Yanqing Li ◽

Bai Ji ◽

Hongqiao Cai ◽

Yahui Liu

Keyword(s):

Liver Cancer ◽

Roc Curve ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Rank Test ◽

P Value ◽

Rna Seq ◽

Cox Regression Analysis

Background and Aims: Emerging studies indicate that long noncoding RNAs (lncRNAs) play a role as prognostic markers in many cancers, including liver cancer. Here, we focused on the lncRNA lung cancer-associated transcript 1 (LUCAT1) for liver cancer prognosis. Methods: RNA-seq and phenotype data were downloaded from the Cancer Genome Atlas (TCGA). Chisquare tests were used to evaluate the correlations between LUCAT1 expression and clinical features. Survival analysis and Cox regression analysis were used to compare different LUCAT1 expression groups (optimal cutoff value determined by ROC). The log-rank test was used to calculate the p-value of the Kaplan-Meier curves. A ROC curve was used to evaluate the diagnostic value. Gene Set Enrichment Analysis (GSEA) was performed, and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanism. Results: Data mining of the TCGA -Liver Hepatocellular Carcinoma (LIHC) RNA-seq data of 371 patients showed the overexpression of LUCAT1 in cancerous tissue. High LUCAT1 expression was associated with age (p=0.007), histologic grade (p=0.009), T classification (p=0.022), and survival status (p=0.002). High LUCAT1 patients had a poorer overall survival and relapse-free survival than low LUCAT1 patients. Multivariate analysis identified LUCAT1 as an independent risk factor for poor survival. The ROC curve indicated modest diagnostic performance. GSEA revealed the related signaling pathways, and the ceRNA network uncovered the underlying mechanism. Conclusion: High LUCAT1 expression is an independent prognostic factor for liver cancer.

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An Analysis of Polymorphisms Within the Wnt Signaling Pathway in Relation to Ovarian Cancer Risk in a Polish Population

Molecular Diagnosis & Therapy ◽

10.1007/s40291-013-0059-y ◽

2013 ◽

Vol 18 (1) ◽

pp. 85-91 ◽

Cited By ~ 25

Author(s):

Adrianna Mostowska ◽

Piotr Pawlik ◽

Stefan Sajdak ◽

Janina Markowska ◽

Monika Pawałowska ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Risk ◽

Wnt Signaling ◽

Signaling Pathway ◽

Wnt Signaling Pathway ◽

Ovarian Cancer Risk ◽

Polish Population

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SERPINE1 associated with remodeling of the tumor microenvironment in colon cancer progression: a novel therapeutic target

BMC Cancer ◽

10.1186/s12885-021-08536-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shaokun Wang ◽

Li Pang ◽

Zuolong Liu ◽

Xiangwei Meng

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Immune Cells ◽

Immune Cell ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

The Relationship

Abstract Background The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. Methods In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. Results By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. Conclusion We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.

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