Methylation of Cancer Stem Cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33114 | GEO | 2011/11/05
SECONDARY ACCESSION(S): PRJNA149357
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the following subset Series: GSE33112: Gene expression in colon cancer stem cells (CSC) cultures identified by Wnt signaling levels GSE33113: AMC colon cancer AJCCII Refer to individual Series
2011-11-05 | E-GEOD-33114 | biostudies-arrayexpress
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Project description:Methylation of Cancer Stem Cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients
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Project description:PurposeThe epithelial-mesenchymal transition (EMT) is a key hallmark of cancer which promotes malignant progression, especially during the process of cancer invasion. A better understanding of EMT will help elucidate the molecular mechanism underlying colorectal cancer (CRC) metastasis and may provide new insights into the identification of potential biomarkers and therapeutic targets.MethodsA series of bioinformatic approaches were combined and identify GLI3 as a potential key regulator in EMT. In vitro experiments were performed to knockdown GLI3 expression in two CRC cell lines and to reveal the oncogenic role of GLI3 in CRC. qRT-PCR and western blot were performed to show the influence of GLI3 in EMT and downstream pathways. The Kaplan-Meier analysis and log-rank test were used to evaluate the prognostic value of GLI3 in CRC patients.ResultsGLI3 was identified as a key regulator in coexpression and protein-protein interaction (PPI) networks involved in EMT. Bioinformatic analyses indicated that GLI3 had a high correlation with EMT markers in CRC. In vitro experiments showed that GLI3 knockdown attenuated the migratory and invasive capacities of CRC cells via influencing EMT property, especially by regulating phosphorylation of ERK signaling pathway. In addition, higher expression of GLI3 predicts worse prognosis in CRC patients.ConclusionsIn summary, we presented the first evidence that GLI3 could promote the migratory and invasive capacities of CRC cells by regulating the EMT process. Our study might provide some useful clues to a better understanding of GLI3 in EMT during CRC progression.
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Project description:Bone morphogenetic proteins (BMPs) both promote and suppress tumorigenesis, and multiple BMP antagonists reportedly contribute to cancer progression. In this study, we demonstrated that the BMP antagonist Chordin-like 2 (CHRDL2) is upregulated in colorectal cancer (CRC) tissues, and that CHRDL2 levels correlate with clinical features of CRC patients, including tumor size, TNM staging, and tumor differentiation. In addition, survival rate and Cox proportional hazards model analyses showed that high CHRDL2 levels correlate with a poor prognosis in CRC. Moreover, CHRDL2 promoted CRC cell proliferation in vitro and in vivo, perhaps through up-regulation of Cyclin D1 and down-regulation of P21. Co-immunoprecipitation assays showed that CHRDL2 bound to BMPs, which inhibited p-Smad1/5, thereby promoting CRC cell proliferation and inhibiting apoptosis. These results suggest CHRDL2 could serve as a biomarker of poor prognosis in CRC, and provide evidence that CHRDL2 acts as an oncogene in human CRC, making it a novel potential therapeutic target.
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Project description:Colorectal cancer is a heterogeneous disease. Although many risk factors are used to predict colorectal cancer patients' prognosis after surgical resection, new prognostic factors are still needed to be defined to promote predictive efficacy of prognosis and further guide therapies. Herein, we identified the prognostic significance of CXCR2 in colorectal cancer patients. We retrospectively analysed 134 patients with colorectal cancer who underwent minimally invasive surgery between 2010 and 2011. The overall cohort was divided into a training set (n = 78) and a validation set (n = 56). We detected CXCR2 expression using immunohistochemical staining and defined the cut-off value using X-tile program. Next, we analysed the association between CXCR2 expression and clinicopathologic features in training and validation sets. High expression of CXCR2 was associated with Dukes stage (P = 0.018), tumor invasion (P = 0.018) and liver metastasis (P = 0.047). Multivariate COX regression analyses confirmed that high CXCR2 level was an independent prognostic risk factor for both overall survival and disease free survival. Kaplan-Meier survival analysis demonstrated that patients with high expression of CXCR2 had a poor overall survival and disease free survival even in low-risk group (I + II). This indicated that CXCR2 can help to refine individual risk stratification. In addition, we established Nomograms of all significant factors to predict 3- or 5-years overall survival and disease free survival. Moreover, we found the combination of CXCR2 and its ligand CXCL5 had more significant value in predicting the prognosis than single CXCR2 factor.
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Project description:Transforming growth factor-beta-induced (TGFBI) serves as a linker protein and plays a role in the activation of morphogenesis, cell proliferation, adhesion, migration, differentiation and inflammation. High expression levels of the human TGFBI gene are correlated with numerous human malignancies. In order to explore the roles of TGFBI in the tumor progression of colorectal cancer, colorectal cancer specimens from 115 patients with strict follow-up were selected for the analysis of TGFBI by immunohistochemistry. The correlations between TGFBI expression and the clinicopathological features of colorectal cancers were evaluated. In the colorectal cancer tissues, TGFBI was mainly localized in the cytoplasm and stroma and scarcely in the nucleus. TGFBI expression in the cytoplasm and stroma was not found to be associated with age, gender, tumor histopathological grading, PT category and tumor location (P > 0.05 for each). However, high TGFBI expression in the cytoplasm and stroma correlated with lymph node metastasis, distant metastasis and Dukes stage (P < 0.05 for each). The survival rate was significantly lower in patients with high TGFBI expression than in those with low TGFBI expression. Furthermore, we found that tumor node metastasis (TNM) staging (HR: 2.963; 95% CI: 1.573-1.664; P = 0.000), differentiation (HR: 1.574; 95% CI: 1.001-2.476; P = 0.049) and high TGFBI cytoplasmic expression (HR: 3.332; 95% CI: 1.410-7.873; P = 0.000) proved to be independent prognostic factors for survival in colorectal cancer. In conclusion, TGFBI plays an important role in the progression of colorectal cancers and it is an independent poor prognostic factor for colorectal cancer patients.
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Project description:BackgroundLncRNA MIR4435-2HG is observed in a variety of cancers, while its role in colorectal cancer is unknown. We aimed to demonstrate the relationship between MIR4435-2HG and colorectal cancer based on The Cancer Genome Atlas (TCGA) database.Materials and methodsPatients with colorectal cancer were collected from TCGA. We compared the expression of MIR4435-2HG in colorectal cancer and normal tissues with Wilcoxon rank sum test, and logistic regression was used to evaluate the relationship between MIR4435-2HG and clinicopathological characters. Moreover, Kaplan-Meier and Cox regression was performed to evaluate the correlation between MIR4435-2HG and survival rate. Gene set enrichment analysis (GSEA) was also conducted to annotate biological function of MIR4435-2HG.ResultsMIR4435-2HG level was elevated in colorectal cancer tissues. Increased level of MIR4435-2HG was significantly correlated with TNM stage (OR = 1.66 for T1/T2 vs. T3/T4; OR = 1.68 for N0 vs. N1/N2), stage (OR = 1.66 for stage 1/2 vs. stage 3/4), and carcinoembryonic antigen level before treatment (OR = 1.70 for <5 vs. ≥5) (all P-value <0.05). High MIR4435-2HG expression had a poorer progression-free survival (p = 0.048), and overall survival (OS) (P = 0.028), which were validated in the GSE92921 and GSE29621 datasets. MIR4435-2HG expression (P = 0.040, HR = 1.955 (95% CI [1.031-3.710])) was independently correlated with OS. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway, the cell surface interactions at the vascular wall, and integrin cell surface interactions were differentially enriched in MIR4435-2HG high expression phenotype.ConclusionsIncreased MIR4435-2HG might be a potential biomarker for the diagnosis and prognosis of colorectal cancer. Moreover, MIR4435-2HG might participate in the development of colorectal cancer via the P38/MAPK and VEGF pathway.
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Project description:BackgroundThe role of meteorin (METRN) in colorectal cancer has not been reported previously. We aimed to explore the relationship between METRN and colorectal cancer (CRC) prognosis.MethodsData were retrieved from the Gene Expression Omnibus database. Gene expression values were log2 transformed and normalized by quantile normalization. Missing values were imputed with the R impute package. Differentially expressed genes were analyzed using the R limma package. METRN expression was compared between normal and CRC tissues and among different stages and subtypes of CRC. We assessed the relationship between METRN and KRAS/BRAF mutations in CRC. Five-year overall (OS), disease-free (DFS), and disease-specific survival (DSS) rates were determined by Kaplan-Meier analysis and analyzed by log-rank test.ResultsMETRN was expressed at a higher level in CRC (p = .0011) than in normal tissues, especially in advanced stages (p = .0343). METRN expression levels were higher in the MSI (dMMR) subtype (p < .001) and usually with BRAF mutations (p < .0001). METRN overexpression was associated with poor prognosis and low OS (p = .01014), DFS (p = .0146), and DSS (p < .0001) rates.ConclusionMETRN overexpression is a predictive factor for poor prognosis in patients with CRC.
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Project description:BackgroundLong noncoding RNAs (lncRNAs) have been suggested to be involved in the development and progression of malignancies. However, the investigation of small nucleolar RNA host gene 20 (SNHG20) on cancer progression remains unknown. The present study aims to explore the clinical significance of SNHG20 and its potential molecular mechanism in colorectal cancer (CRC).MethodsQuantitative real-time PCR (qRT-PCR) was used to measure the SNHG20 expression in a total of 107 CRC tissues and CRC cell lines. Loss of function approach was employed to explore the biological roles of SNHG20 in vitro. Its potential molecular mechanism was further verified by western blotting and qRT-PCR.ResultsThe results suggested that SNHG20 expression was significantly upregulated in CRC tissues compared to corresponding normal tissues from 107 CRC patients. High expression of SNHG20 was remarkably associated with advanced TNM stage in patients with CRC. Multivariate analyses unraveled that SNHG20 expression was an independent prognostic factor for overall survival in CRC patients. Further functional assays revealed that knockdown of SNHG20 suppressed cell proliferation, invasion and migration, and cell cycle progression in CRC cells. Moreover, SNHG20 regulated cell growth through modulation of a series of cell cycle-associated genes.ConclusionsOur findings suggest that dysregulation of SNHG20 participates in CRC progression and may serve as a potential therapeutic target in CRC patients.
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