Prognostic and Predictive Value of Cadherin 11 for Patients with Gastric Cancer and Its Correlation with Tumor Microenvironment: Results from Microarray Analysis

Feng, Zhijun; Xue, Li; Ren, Zhijian; Feng, Jie; He, Xiaodong; You, Chongge

doi:10.1155/2020/8107478

Cited by 7 publications

(6 citation statements)

References 65 publications

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“…The AJCC pathological tumor stage and nuclear grade are commonly used for prognostic diagnoses in patients with RCC. Our statistical analysis of clinicopathological features in patients with RCC showed a positive correlation between the CDH11 methylation status and the tumor stage or nuclear grade, which was consistent with the conclusions obtained from gastric cancer and non-muscle invasive bladder cancer [28][29][30][31] . Our data in the subsequently functional trails also showed that ectopic expression of CDH11 gene inhibited the proliferation, migration and invasion in RCC cell lines.…”

Section: Discussionsupporting

confidence: 89%

Aberrant Methylation of the 16q22.1 Tumor Suppressor Gene CDH11 Promotes Tumorigenesis and Progression of Renal Cell Carcinoma through NF-kB Pathway

Xu¹,

Song²,

Luo³

et al. 2020

Preprint

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Background: To discover new epigenetic biomarkers for early cancer detection. The CDH11 gene has been reported as a critical tumor suppressor gene (TSG) for multiple tumors, although it has not yet been reported in renal cell carcinoma (RCC). We explored its epigenetic alteration in RCC and analyzed the possible biological function and mechanism in tumorigenesis and progression of RCC.Materials and Methods: We examined CDH11 gene expression and methylation using semiquantitative reverse transcriptase PCR (RT-PCR) and methylation-specific polymerase chain reaction (MSP) in RCC cell lines before and after treatment with 5-aza-2’-deoxycytidine (5-Aza). MSP was further applied to 93 RCC primary tumors, and the relationship between CDH11 gene methylation and clinicopathological features was discussed. A selection of the cell lines and specimens was subsequently examined using bisulfite genomic sequencing (BGS) and real-time PCR. Meanwhile, assays of cell viability, colony formation, migration and invasion, wound healing, and western blot were performed to confirm the tumor-suppressive function and mechanism of CDH11 gene.Results: CDH11 gene methylation was detected in 4 of 5 RCC cell lines with silenced expressions. Treatment with 5-Aza reversed methylation and restored CDH11 gene expression. Aberrant methylation was further detected in 41 of the 93 (44.1%) primary tumors. Furthermore, CDH11 gene methylation was significantly associated with tumor stage and nuclear grade in patients with RCC (p<0.05). Due to the phenomenon of aberrant methylation, ectopic low-level expression of CDH11 gene could result in promotion of tumorigenesis and progression in RCC cell lines, which might be mediated through NF-kB pathway. Conclusions: The CDH11 gene is often down-regulated by aberrant promoter methylation in RCC cell lines and primary tumors, indicating its critical role as a TSG in RCC. It may be involved in the tumorigenesis and progression in RCC through NF-kB pathway, thus which could potentially serve as a novel biomarker and therapeutic target for RCC.

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Section: Discussionsupporting

confidence: 89%

Aberrant Methylation of the 16q22.1 Tumor Suppressor Gene CDH11 Promotes Tumorigenesis and Progression of Renal Cell Carcinoma through NF-kB Pathway

Xu¹,

Song²,

Luo³

et al. 2020

Preprint

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“…Kaplan-Meier analysis and the log-rank test were applied to determine the survival curves. Correlations between key genes, infiltrating cell types, and gene markers were established by Spearman's correlation, and correlation strength was classified according to the absolute value of the partial correlation coefficient as follows: 0.00-0.19 "a negligible correlation"; 0.20-0.39 "a weak correlation"; 0.40-0.59 "a moderate correlation"; 0.60-0.79 "a strong correlation"; and 0.80-1.0 "a very strong correlation" [40,41]. The results were considered to have statistical significance when P < 0:05.…”

Section: Analyses Of Key Gene-tumor Microenvironment (Tme)mentioning

confidence: 99%

“…Two molecular modules were identified using MCODE, the most important of which contained 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK), as visualized in Figure 4(b), which also revealed that this molecular module plays an important role in the process of hepatocarcinogenesis. HCV-related HCC (53) vs. HCV-related hepatitis (40) HBV-related HCC (39) vs.…”

Section: Ppi Network and Molecularmentioning

confidence: 99%

Bioinformatic Evidence Reveals that Cell Cycle Correlated Genes Drive the Communication between Tumor Cells and the Tumor Microenvironment and Impact the Outcomes of Hepatocellular Carcinoma

Chen

Feng

Zhou

et al. 2021

BioMed Research International

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Hepatocellular carcinoma (HCC) is an aggressive cancer type with poor prognosis; thus, there is especially necessary and urgent to screen potential prognostic biomarkers for early diagnosis and novel therapeutic targets. In this study, we downloaded target data sets from the GEO database, and obtained codifferentially expressed genes using the limma R package and identified key genes through the protein–protein interaction network and molecular modules, and performed GO and KEGG pathway analyses for key genes via the clusterProfiler package and further determined their correlations with clinicopathological features using the Oncomine database. Survival analysis was completed in the GEPIA and the Kaplan–Meier plotter database. Finally, correlations between key genes, cell types infiltrated in the tumor microenvironment (TME), and hypoxic signatures were explored based on the TIMER database. From the results, 11 key genes related to the cell cycle were determined, and high levels of these key genes’ expression were focused on advanced and higher grade status HCC patients, as well as in samples of TP53 mutation and vascular invasion. Besides, the 11 key genes were significantly associated with poor prognosis of HCC and also were positively related to the infiltration level of MDSCs in the TME and the HIF1A and VEGFA of hypoxic signatures, but a negative correlation was found with endothelial cells (ECs) and hematopoietic stem cells. The result determined that 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK) could play a vital role in the pathogenesis of HCC, drive the communication between tumor cells and the TME, and act as probably promising diagnostic, therapeutic, and prognostic biomarkers in HCC patients.

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“…CDH11 is known as a transmembrane protein mediating cellular adhesion and a hallmark of mesenchymal phenotype that is broadly expressed in multiple cell types undergoing EMT including breast [ 17 , 18 , 20 , 21 ], prostate [ 22 , 23 ], brain [ 40 ], renal [ 24 ], bone [ 25 ], bladder [ 41 ], ovary [ 42 ] and gastric [ 43 , 44 ] cancer cells. Although some studies reported that CDH11 is frequently methylated and silenced in certain types of cancers [ 45 , 46 , 47 ], cumulative emerging evidence suggests that CDH11 may play a critical role in promoting tumorigenesis and metastasis in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Cadherin‐11 increases tumor cell proliferation and metastatic potential via Wnt pathway activation

Liu,

Lei,

Samuel

et al. 2023

Molecular Oncology

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During epithelial‐mesenchymal transition (EMT) in cancer progression, tumor cells switch cadherin profile from E‐cadherin to cadherin‐11 (CDH11), which is accompanied by increased invasiveness and metastatic activity. However, the mechanism through which CDH11 may affect tumor growth and metastasis remains elusive. Here, we report that CDH11 was highly expressed in multiple human tumors and was localized on the membrane, in the cytoplasm and, surprisingly, also in the nucleus. Interestingly, β‐catenin remained bound to carboxy‐terminal fragments (CTFs) of CDH11, the products of CDH11 cleavage, and co‐localized with CTFs in the nucleus in the majority of breast cancer samples. Binding of β‐catenin to CTFs preserved β‐catenin activity, whereas inhibiting CDH11 cleavage led to β‐catenin phosphorylation and diminished Wnt signaling, similar to CDH11 knockout. Our data elucidates a previously unknown role of CDH11, which serves to stabilize β‐catenin in the cytoplasm and facilitate its translocation to the nucleus, resulting in activation of Wnt signaling, with subsequent increased proliferation, migration and invasion potential.

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Prognostic and Predictive Value of Cadherin 11 for Patients with Gastric Cancer and Its Correlation with Tumor Microenvironment: Results from Microarray Analysis

Cited by 7 publications

References 65 publications

Aberrant Methylation of the 16q22.1 Tumor Suppressor Gene CDH11 Promotes Tumorigenesis and Progression of Renal Cell Carcinoma through NF-kB Pathway

Aberrant Methylation of the 16q22.1 Tumor Suppressor Gene CDH11 Promotes Tumorigenesis and Progression of Renal Cell Carcinoma through NF-kB Pathway

Bioinformatic Evidence Reveals that Cell Cycle Correlated Genes Drive the Communication between Tumor Cells and the Tumor Microenvironment and Impact the Outcomes of Hepatocellular Carcinoma

Cadherin‐11 increases tumor cell proliferation and metastatic potential via Wnt pathway activation

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