scholarly journals DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Jianyu Yang ◽  
Yongsheng Jiang ◽  
Ruizhe He ◽  
Wei Liu ◽  
Minwei Yang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Immunity ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Gene Set Enrichment Analysis ◽  
Cellular Migration ◽  
Ductal Adenocarcinoma ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating cancer types despite the improvement of modern medicine. In our present study, we found that dickkopf-related protein 2 (DKK2) shares a higher expression in PDAC compared with adjacent pancreas tissue in tissue microarray. In addition, an elevated expression of DKK2 predicts poorer prognosis of patients and positively correlated with poor tumor differentiation. Multivariate Cox regression analysis was also performed and confirmed that the expression of DKK2 is an independent prognostic factor in PDAC. A high expression of DKK2 correlates with cell migration and epithelial mesenchymal transition based on gene set enrichment analysis (GSEA) while knockdown of DKK2 in PDAC cells resulted in impaired cellular migration. Furthermore, GSEA predicts negative correlation between tumor immunity invasion and DKK2 expression. We then confirmed these results and demonstrated that a higher expression of DKK2 imparts the recruitment of CD8+ T cells. Our work suggested that DKK2 imparts tumor immune evasion and is associated with poor prognosis in pancreatic ductal adenocarcinoma.

scholarly journals Identification of Epithelial–Mesenchymal Transition-Related Prognostic lncRNAs Biomarkers Associated With Melanoma Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Bo Xiao ◽  
Liyan Liu ◽  
Zhuoyuan Chen ◽  
Aoyu Li ◽  
Pingxiao Wang ◽  
...  
Keyword(s):  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Enrichment Analysis ◽  
Roc Curves ◽  
Risk Groups ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial–mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database (N = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.

scholarly journals Exploration of the Key Proteins in the Normal-Adenoma-Carcinoma Sequence of Colorectal Cancer Evolution Using In-Depth Quantitative Proteomics

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Yin Zhang ◽  
Chun-Yuan Li ◽  
Wei Ge ◽  
Yi Xiao
Keyword(s):  
Colorectal Cancer ◽  
Quantitative Proteomics ◽  
Prognostic Value ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Gene Set Enrichment Analysis ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Proteomic Data

Purpose. In most cases, the carcinogenesis of colorectal cancer (CRC) follows the normal-adenoma-carcinoma (N-A-C) sequence. In this study, we aimed to identify the key proteins in the N-A-C sequence. Methods. Differentially expressed proteins (DEPs) in normal, adenoma, and carcinoma tissues were identified using the Tandem Mass Tag- (TMT-) based quantitative proteomics approach. The landscape of proteomic variation in the N-A-C sequence was explored using gene set enrichment analysis (GSEA) and Proteomaps. Key proteins in the N-A-C sequence were identified, verified, and validated based on our proteomic data, external proteomic data, and external transcriptomic data in the ProteomeXchange, CPTAC, GEO, and TCGA databases. The prognostic value of the key proteins in our database was evaluated by univariate and multivariate Cox regression analysis. The effects of the key proteins on adenoma organoids and colorectal cancer cells were explored in functional studies. Results. Based on our proteomic profiles, we identified 1,294 DEPs between the carcinoma (CG) and normal (NG) groups, 919 DEPs between the adenoma group (AG) and NG, and 1,030 DEPs between the CG and AG. Ribosome- and spliceosome-related pathways were mainly enriched in the N-A process. Extracellular matrix- and epithelial-mesenchymal transition- (EMT-) related pathways were mainly enriched in the A-C process. RRP12 and SERPINH1 were identified, verified, and validated as candidate key proteins in the N-A and A-C processes, respectively. Furthermore, RRP12 and SERPINH1 knockdown impeded the viability and proliferation of adenoma organoids. SERPINH1 was validated as a risk factor for disease-free survival (DFS) based on the TCGA and our database, whereas RRP12 did not show prognostic value. SERPINH1 knockdown was accompanied by EMT-related protein variation, increased apoptosis, and reduced proliferation, invasion, and migration of CRC cells in vitro. Conclusions. RRP12 and SERPINH1 may play an important role in the N-A and A-C processes, respectively. Furthermore, SERPINH1 showed favorable prognostic value for DFS in CRC patients. We speculate that SERPINH1 might promote not only the A-C process but also the development of CRC.

scholarly journals Upregulated SMAD3 promotes epithelial–mesenchymal transition and predicts poor prognosis in pancreatic ductal adenocarcinoma

2014 ◽  
Vol 94 (6) ◽  
pp. 683-691 ◽  
Author(s):  
Ken Yamazaki ◽  
Yohei Masugi ◽  
Kathryn Effendi ◽  
Hanako Tsujikawa ◽  
Nobuyoshi Hiraoka ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Ductal Adenocarcinoma ◽  
Mesenchymal Transition

scholarly journals Prognostic Impact of Autophagy and Immunity Related Biomarker for Uveal Melanoma

2021 ◽  
Author(s):  
Huibin Du ◽  
Yan He ◽  
Wei Lu ◽  
Qi Wan
Keyword(s):  
High Risk ◽  
Uveal Melanoma ◽  
Risk Model ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Prognostic Impact ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis

Abstract Background: Autophagy and immunity related genes serve crucial roles in carcinogenesis, but little is known about the prognostic impact for uveal melanoma (UM).Methods: Autophagy related and immunity related genes (AIRGs) expression data of 80 UM patients were obtained from the cancer genome atlas project (TCGA) database. Next, univariate cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithms were applied to build a robust AIRGs signature in TCGA and validated in another two independent datasets. Besides, UM patients classified into two subgroups based on the risk model. Differences of clinical outcome, tumor microenvironment and the likelihood of chemotherapeutic response were further explored.Results: In total, a 4-AIRGs signature was constructed and validated in various datasets, which can robustly predict patients’ metastasis-free survival (MFS) and overall survival (OS) and is an independent prognostic factor in UM. The UM patients can be classified into high and low risk subgroups by applied risk score system. The high risk group have poor clinical outcomes, higher CD8+ T cell and macrophage immune-infiltrating and more sensitive to chemotherapies. In addition, Gene Set Enrichment Analysis (GSEA) analysis revealed that hallmark epithelial-mesenchymal transition and KRAS pathways are commonly enriched in high-risk expression phenotype.Conclusion: Thus, our findings provide a new clinical strategy for the accurate diagnosis and identify a novel prognostic autophagy and immunity associated biomarker for the treatment of uveal melanoma.

scholarly journals Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Pancreatic Ductal Adenocarcinoma

2020 ◽  
Author(s):  
Qianhui Xu ◽  
Yuxin Wang ◽  
Wen Huang
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Risk Score ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Cox Regression Analysis

Abstract Background: An increasing body of evidence has suggested that long non-coding RNAs (lncRNAs) can serve as essential regulators in cancer immunity. We aimed to establish a robust immune-associated lncRNA signature for pancreatic ductal adenocarcinoma (PDAC) outcome prediction to enhance prognostic accuracy.Methods: Pancreatic cancer samples were obtained from the The Cancer Genome Atlas (TCGA) project. Immune‐related lncRNAs displaying significant association with overall survival (OS) were screened through univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. The prediction reliability was further estimated in the internal validation set and combination set. Gene set enrichment analysis (GSEA) of the lncRNA model risk score was performed for functional annotation. The correlation between immune checkpoint inhibitors and this signature was examined. Results: 5 immune-related lncRNAs were confirmed to establish five‐immune-related lncRNAs prognostic signature. The constructed risk model showed significant correlation with PDAC OS. The area under the curve (AUC) for this lncRNA model was up to 0.747. This immune‐related lncRNA signature was correlated with disease progression and worse survival and was an independent prognostic biomarker. Our signature mediated chondrocyte development, laminin binding and so forth. This risk score model was associated with immune cell infiltration (i.e., CD4 T cells, etc.,) and immune checkpoint blockade (ICB) immunotherapy‐related molecules (i.e., PDCD1 and CTLA4).Conclusion: The immune‐related lncRNA signature we established possesses latent prognostic value for patients with PDAC and may have the potential to measure the response to ICB immunotherapy, which could guide for immunological treatment in PDAC.

scholarly journals Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 410-418
Author(s):  
Ping Tian ◽  
Chen Zhang ◽  
Cailing Ma ◽  
Lu Ding ◽  
Ning Tao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Vascular Invasion ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Clinicopathological Characteristics ◽  
Clinical Staging ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis

Abstract The aim of this study was to evaluate the association of the chromobox homologue 7 (CBX7) expression with the epithelial–mesenchymal transition in cervical cancer (CC), as well as with the disease prognosis. CBX7, E-cadherin (E-cad), and vimentin (VIM) expression levels were detected with immunohistochemistry. The relationship between the expression of CBX7, E-cad, and VIM expression and conventional clinicopathological characteristics of CC were evaluated. The positive expression rates of CBX7 and E-cad in the CC tissues were lower than the adjacent non-tumorous cervical tissues. Moreover, the VIM expression level was higher. The CBX7 expression was positively correlated with the E-cad expression, whereas was negatively correlated with the VIM expression. Furthermore, CBX7 was associated with the disease clinical staging, histological differentiation, lymph node metastasis, and vascular invasion. Patients with negative CBX7 expression showed decreased overall survival rates compared with those with low or high CBX7 expression. Multivariate Cox regression analysis indicated that the decreased CBX7 expression was an independent predictor for the poor prognosis of CC. In conclusion, the absence of CBX7 is associated with the histologic differentiation, lymphatic metastasis, vascular invasion, and poor prognosis of CC. CBX7 may be an independent prognostic factor for the prognosis of CC patients.

scholarly journals Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

2021 ◽  
Vol 12 (1) ◽  
pp. 67-75
Author(s):  
Ying Yang ◽  
Jin Wang ◽  
Shihai Xu ◽  
Fei Shi ◽  
Aijun Shan
Keyword(s):  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Gliomas ◽  
Strongly Correlated ◽  
Who Grade ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
R Language ◽  
Biological Adhesion ◽  
Tcga Dataset

Abstract Background Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. Methods Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses. Results CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age. Conclusions CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.

scholarly journals Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2

Oncogene ◽  
2021 ◽  
Vol 40 (17) ◽  
pp. 3164-3179
Author(s):  
Yang Liu ◽  
Tianchi Tang ◽  
Xiaosheng Yang ◽  
Peng Qin ◽  
Pusen Wang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Noncoding Rna ◽  
Pancreatic Tumor ◽  
Epithelial Mesenchymal Transition ◽  
Noncoding Rnas ◽  
Ductal Adenocarcinoma ◽  
Overall Survival Rate ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.

FAM196B promotes proliferation and migration via regulating epithelial-mesenchymal transition in esophageal cancer

2021 ◽  
pp. 1-8
Author(s):  
Haifeng Xia ◽  
Fang Hu ◽  
Liangbin Pan ◽  
Chengcheng Xu ◽  
Haitao Huang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Western Blot ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Ec Cells ◽  
And Migration ◽  
Proliferation And Migration

BACKGROUND: EC (esophageal cancer) is a common cancer among people in the world. The molecular mechanism of FAM196B (family with sequence similarity 196 member B) in EC is still unclear. This article aimed to clarify the role of FAM196B in EC. METHODS: The expression of FAM196B in EC tissues was detected using qRT-PCR. The prognosis of FAM196B in EC patients was determined by log-rank kaplan-Meier survival analysis and Cox regression analysis. Furthermore, shRNA was used to knockdown the expression of FAM196B in EC cell lines. MTT, wound healing assays and western blot were used to determine the role of FAM196B in EC cells. RESULTS: In our research, we found that the expression of FAM196B was up-regulated in EC tissues. The increased expression of FAM196B was significantly correlated with differentiation, lymph node metastasis, stage, and poor survival. The proliferation and migration of EC cells were inhibited after FAM196B-shRNA transfection in vitro and vivo. The western blot result showed that FAM196B could regulate EMT. CONCLUSION: These results suggested that FAM196B severs as an oncogene and promotes cell proliferation and migration in EC. In addition, FAM196B may be a potential therapeutic target for EC patients.

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