scholarly journals Comprehensive Analysis of The Significance of Hypoxia-Related Genes in Ovarian Cancer

2021 ◽  
Author(s):  
Wancheng Zhao ◽  
Lili Yin
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Principal Component ◽  
Vital Role ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Consensus Clustering ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Pca Algorithm

Abstract Background: Hypoxia-related genes have been reported to play important roles in a variety of cancers. However, their roles in ovarian cancer (OC) have remained unknown. Our aim was to explore the significance of hypoxia-related genes in OC patients.Methods: In this study, 15 hypoxia-related genes were screened from The Cancer Genome Atlas (TCGA) database to group the ovarian cancer patients using the consensus clustering method. Principal component analysis (PCA) was used to calculate the hypoxia score to quantify the hypoxic status. Results: The OC patients were divided into two hypoxia statuses based on the expression level of the 15 hypoxia-related genes. Most hypoxia-related genes were more highly expressed in the cluster.A group. We also found that patients in the cluster.A group exhibited higher expression level of immune checkpoint-related genes, epithelial-mesenchymal transition-related genes, and immune activation-related genes, as well as elevated immune infiltrates. PCA algorithm indicated that the cluster.A group had higher hypoxia scores.Conclusions: In summary, our research elucidated the vital role of hypoxia-related genes in immune infiltrates of OC. Our investigation of hypoxic status may be able to improve the efficacy of immunotherapy for OC.

scholarly journals Comprehensive Analysis of The Significance of Hypoxia-Related Genes in Ovarian Cancer

2021 ◽  
Author(s):  
Wancheng Zhao ◽  
Lili Yin
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Principal Component ◽  
Vital Role ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Pca Algorithm

Abstract Background: Hypoxia-related genes have been reported to play important roles in a variety of cancers. However, their roles in ovarian cancer (OC) have remained unknown. The aim of our research was to explore the significance of hypoxia-related genes in OC patients.Methods: In this study, 15 hypoxia-related genes were screened from The Cancer Genome Atlas (TCGA) database to group the ovarian cancer patients using the consensus clustering method. Principal component analysis (PCA) was performed to calculate the hypoxia score for each patient to quantify the hypoxic status. Results: The OC patients from TCGA-OV dataset were divided into two distinct hypoxia statuses (cluster.A and cluster.B) based on the expression level of the 15 hypoxia-related genes. Most hypoxia-related genes were expressed more highly in the cluster.A group than in the cluster.B group. We also found that patients in the cluster.A group exhibited higher expression of immune checkpoint-related genes, epithelial-mesenchymal transition-related genes, and immune activation-related genes, as well as elevated immune infiltrates. PCA algorithm indicated that patients in the cluster.A group had higher hypoxia scores than that in in the cluster.B group.Conclusions: In summary, our research elucidated the vital role of hypoxia-related genes in immune infiltrates of OC. Our investigation of hypoxic status may be able to improve the efficacy of immunotherapy for OC.

scholarly journals HDAC9 Is Preferentially Expressed in Dedifferentiated Hepatocellular Carcinoma Cells and Is Involved in an Anchorage-Independent Growth

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2734
Author(s):  
Keita Kanki ◽  
Ryota Watanabe ◽  
Le Nguyen Thai ◽  
Chun-Hao Zhao ◽  
Kyoko Naito
Keyword(s):  
Hepatocellular Carcinoma ◽  
Histone Deacetylases ◽  
Epithelial Mesenchymal Transition ◽  
Cell Transformation ◽  
The Cancer Genome Atlas ◽  
Hepatic Differentiation ◽  
Differentiation Markers ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Hcc Cells

Aberrant activation of histone deacetylases (HDACs) is one of the causes of tumor cell transformation in many types of cancer, however, the critical HDAC responsible for the malignant transformation remain unclear. To identify the HDAC related to the dedifferentiation of hepatocellular carcinoma (HCC) cells, we investigated the expression profile of HDACs in differentiated and undifferentiated hepatoma cells. We found that HDAC9, a member of the class II HDAC, is preferentially expressed in undifferentiated HCC cells. Analysis of 373 HCC patients in The Cancer Genome Atlas (TCGA) database revealed that the expression of HDAC9 mRNA positively correlated with the markers of mesenchymal phenotype and stemness, and conversely, negatively correlated with hepatic differentiation markers. HDAC9 was transcriptionally upregulated in epithelial–mesenchymal transition (EMT)-induced HCC cells treated with TGF-β. Genetic and pharmacological inhibition of HDAC9 in undifferentiated HCC cells showed decreased sphere-forming activity, which indicates an ability of anchorage-independent cell growth and self-renewal. We also showed that aldehyde dehydrogenase 1A3 (ALDH1A3) was downregulated in HDAC9-suppressing cells, and ALDH inhibitor disulfiram significantly decreased the sphere formation of undifferentiated HCC cells. Together, our data provide useful information for the development of HDAC9-specific inhibitors for the treatment of HCC progression.

scholarly journals Abnormally expressed JunB transactivated by IL-6/STAT3 signaling promotes uveal melanoma aggressiveness via epithelial–mesenchymal transition

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Chaoju Gong ◽  
Jie Shen ◽  
Zejun Fang ◽  
Lei Qiao ◽  
Ruifang Feng ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Epithelial Marker ◽  
Cancer Genome Atlas

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and it carries a high risk of metastasis and mortality. Various proinflammatory cytokines have been found to be significantly increased in the aqueous humor or vitreous fluid of UM patients; however, the role of these cytokines in UM metastasis remains elusive. In the present study, we found that long-term interleukin (IL)-6 exposure promoted the migration and invasion of UM cells, diminished cell–cell adhesion, and enhanced focal adhesion. Moreover, IL-6 treatment decreased the membranous epithelial marker TJP1 and increased the cytoplasmic mesenchymal marker Vimentin. Further investigation demonstrated that JunB played a critical role in IL-6-induced UM epithelial–mesenchymal transition (EMT). In UM cells, the expression of JunB was significantly up-regulated during the IL-6-driven EMT process. Additionally, JunB induction occurred at the transcriptional level in a manner dependent on phosphorylated STAT3, during which activated STAT3 directly bound to the JunB promoter. Importantly, the knockdown of STAT3 prevented the IL-6-induced EMT phenotype as well as cell migration and invasion, whereas JunB overexpression recovered the attenuated aggressiveness of UM cells. Similarly, with IL-6 stimulation, the stable overexpression of JunB strengthened the migratory and invasive capabilities of UM cells and induced the EMT-promoting factors (Snail, Twist1, matrix metalloproteinase (MMP)-2, MMP-14, and MMP-19). Analysis of The Cancer Genome Atlas (TCGA) database indicated that JunB was positively correlated with IL-6 and STAT3 in UM tissues. The present study proposes an IL-6/STAT3/JunB axis leading to UM aggressiveness by EMT, which illustrates the negative side of inflammatory response in UM metastasis.

scholarly journals ITGA3 Is a Reliable Biomarker and Putative Therapeutic Target for Glioma

2020 ◽  
Author(s):  
Qing Zhang ◽  
Chen Zhu ◽  
Gefei Guan ◽  
Shuai Shen ◽  
Yunhe Han ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Glioma Cells ◽  
The Cancer Genome Atlas ◽  
Integrin Subunit ◽  
Central Nervous System Tumor ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Background: Glioma is the most prevalent and malignant primary central nervous system tumor in adults. As a member of the integrin alpha chain family of proteins, integrin subunit alpha 3 (ITGA3) has been found to play a critical role in the occurrence and progression of several cancers, including lung, ovarian, and pancreatic cancers. However, the role of ITGA3 in glioma remains unclear.Methods: The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), REMBRANDT, GSE16011, GSE59612, and GSE4290 datasets were used to analyze relevant characteristics of ITGA3 in glioma. R language and GraphPad Prism 7.00 were employed as major tools for statistical analysis and graph manipulation.Results: We identified that ITGA3 expression was upregulated in glioma and related to unfavorable outcomes of glioma patients. Expression of ITGA3 also tended to be enriched in aggressive subtypes of glioma. We demonstrated that expression of ITGA3 was negatively correlated with glioma purity. In gliomas with high ITGA3 expression, the anti-glioma immune response was inhibited. ITGA3 also regulated angiogenesis within the glioma microenvironment and promoted the epithelial–mesenchymal transition (EMT) and autophagy of glioma cells. GSEA analysis revealed that ITGA3 could activate ERK1/2 and PI3K/AKT/mTOR pathways.Conclusion: Our data suggested that ITGA3 promoted the malignant progression of glioma by regulating the immunity of glioma as well as the EMT and autophagy of glioma cells, which could act as a therapeutic target for glioma.

scholarly journals Aging-Related Tumor Microenvironment Changes Could Worsen The Prognosis of GBM Patients

2020 ◽  
Author(s):  
Hongwang Song ◽  
Xiaojun Fu ◽  
Chenxing Wu ◽  
Shouwei Li
Keyword(s):  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Close Correlation ◽  
Underlying Mechanism ◽  
The Cancer Genome Atlas ◽  
Future Research ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Differential Expressed Genes ◽  
Genome Atlas

Abstract Background: Glioblastoma multiforme (GBM) is the most malignant tumor in human brain, with highly heterogeneity among different patients. Age could function as an incidence and prognosis risk factor for many tumors.Method: A series of bioinformatic experiments were conducted to evaluate the differences of incidence, differential expressed genes, enriched pathways with the data from Surveillance, Epidemiology, and End Results (SEER) program, the cancer genome atlas (TCGA) and Chinese glioma genome atlas (CGGA) project.Results: We discovered in our present study that distinct difference of incidence and prognosis of different aged GBM patients. By a series of bioinformatic method, we found that the tumor associated fibroblasts (TAFs) was the most crucial tumor microenvironment (TME) component that led to this phenomenon. Epithelial-mesenchymal transition (EMT) could be the mechanism by which TAFs regulate the progression of GBM. Conclusion: We have proposed a close correlation between age and GBM incidence and prognosis, and propose the underlying mechanism behind this correlation by mining different databases, which laid the foundation for future research.

scholarly journals Aging-related tumor associated fibroblasts changes could worsen the prognosis of GBM patients

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hongwang Song ◽  
Xiaojun Fu ◽  
Chenxing Wu ◽  
Shouwei Li
Keyword(s):  
Risk Factor ◽  
Epithelial Mesenchymal Transition ◽  
Close Correlation ◽  
Underlying Mechanism ◽  
The Cancer Genome Atlas ◽  
Future Research ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Differential Expressed Genes ◽  
Genome Atlas

Abstract Background Glioblastoma multiforme (GBM) is the most malignant tumor in human brain, with highly heterogeneity among different patients. Age could function as an incidence and prognosis risk factor for many tumors. Method A series of bioinformatic experiments were conducted to evaluate the differences of incidence, differential expressed genes, enriched pathways with the data from Surveillance, Epidemiology, and End Results (SEER) program, the cancer genome atlas (TCGA) and Chinese glioma genome atlas (CGGA) project. Results We discovered in our present study that distinct difference of incidence and prognosis of different aged GBM patients. By a series of bioinformatic method, we found that the tumor associated fibroblasts (TAFs) was the most crucial tumor microenvironment (TME) component that led to this phenomenon. Epithelial-mesenchymal transition (EMT) could be the mechanism by which TAFs regulate the progression of GBM. Conclusion We have proposed a close correlation between age and GBM incidence and prognosis, and propose the underlying mechanism behind this correlation by mining different databases, which laid the foundation for future research.

Differential Expression Pattern of Epithelial Mesenchymal Transition Gens; AXL, GAS6, Claudin-1, and Cofilin-1, in Different Stages of Epithelial Ovarian Cancer

2020 ◽  
Author(s):  
Elham HASSANI ◽  
Mahmood SHEKARI KHANIANI ◽  
Mojtaba SAFFARI ◽  
Amirnader EMAMI RAZAVI ◽  
Reza SHIRKOOHI ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Expression Pattern ◽  
Epithelial Mesenchymal Transition ◽  
Tnm Staging ◽  
Expression Level ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Differential Expression Pattern

Background: Epithelial ovarian cancer (EOC), is the fatal form of gynecological cancer. Almost 70% of ovarian cancer patients are detected at an advanced stage (III-IV) with metastases. Epithelial‑mesenchymal transition (EMT) is a critical process associated with metastasis. This study investigated the expression levels of AXL, GAS6, Claudin-1, and Cofilin-1, as genes involved in EMT in relation to clinicopathologic features in ovarian cancer patients. Methods: In this descriptive study, 78 ovarian epithelial cancer patients were enrolled. Samples were provided by the Iran National Tumor Bank, founded by the Cancer Institute of Tehran University of Medical Sciences in 2017. The expression levels of AXL, GAS6, Claudin-1, and Cofilin-1 genes were investigated in a fresh, frozen tumor sample and normal adjacent tissue by real-time PCR (RT-PCR). Results: Findings showed a significant relationship between the overexpression of AXL and TNM staging (P=0.03). The expression level of GAS6 decreased in more advanced stages (P=0.01). There is a negative relationship between Cofilin-1 expression level and TNM staging (P=0.002). Claudin-1 expression level was higher in low stages compared with that in high stages (P=0.01). There was no relationship between gene expression levels of target genes with size and grade of the tumor. Conclusion: Given the importance of these genes in EMT, alteration in their expression pattern can contribute to the progression of the disease and distant metastasis of cancer cells. Additionally, knowing the alteration pattern of these genes expression can help to better understanding and prediction of the prognosis of EOC.

scholarly journals Functional implications of PABPC1 in the development of ovarian cancer

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 805-815
Author(s):  
Cong Feng ◽  
Yan-Hua Han ◽  
Na Qi ◽  
Jia Li ◽  
Qing-Hua Sheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Data Set ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Abstract This research aimed to probe the expression characteristics of poly(A)-binding protein cytoplasmic 1 (PABPC1) and its role on the phenotype of ovarian cancer (OC) cells and to further investigate the possible underlying mechanism. The expression of PABPC1 was analyzed according to the data from gene expression omnibus, The Cancer Genome Atlas (TCGA) and Oncomine databases and the RNA sequencing data set from TCGA were downloaded for evaluating the prognostic values. We revealed that compared with the healthy samples, PABPC1 was upregulated in OC samples. High expression of PABPC1 had a connection with a shorter survival for patients with OC. Loss and gain of function assays revealed that silencing PABPC1 significantly suppressed the viability, invasion and migration of SK-OV-3 cells, while PABPC1 overexpression in A2780 cells showed the reverse outcomes. Moreover, Western blot demonstrated that silencing PABPC1 notably inactivated the epithelial–mesenchymal transition (EMT) process, while upregulation of PABPC1 promoted the mitigation of epithelial phenotype and the acquisition of mesenchymal phenotype. Taken together, PABPC1 was upregulated in OC cells and served as a carcinogene to promote the OC cell growth and invasion partly by modulating the EMT process, which implied that PABPC1 might be considered as a useful biomarker for OC therapeutics.

scholarly journals PGK1 Is a Key Target for Anti-Glycolytic Therapy of Ovarian Cancer: Based on the Comprehensive Analysis of Glycolysis-Related Genes

2021 ◽  
Vol 11 ◽  
Author(s):  
Rui Gou ◽  
Yuexin Hu ◽  
Ouxuan Liu ◽  
Hui Dong ◽  
Lingling Gao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Phosphoglycerate Kinase ◽  
Expression Level ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Research Perspective ◽  
New Research

Reprogramming of energy metabolism is a key hallmark of cancer, which provides a new research perspective for exploring the development of cancer. However, the most critical target of anti-glycolytic therapy for ovarian cancer remains unclear. Therefore, in the present study, Oncomine, GEPIA, and HPA databases, combined with clinical specimens of different histological types of ovarian cancer were used to comprehensively evaluate the expression levels of glycolysis-related metabolite transporters and enzymes in ovarian cancer. We selected phosphoglycerate kinase 1 (PGK1), which showed the greatest prognostic value in the Kaplan-Meier Plotter database, for subsequent validation. Immunochemistry assays confirmed that PGK1 was highly expressed in ovarian cancer. The PGK1 expression level was an independent risk factor for the survival and prognosis of patients with ovarian cancer. Functional analysis showed that the PGK1 expression level was positively correlated with the infiltration of neutrophils. Cell experiments confirmed that inhibiting PGK1 expression in ovarian cancer cells could reduce the epithelial-mesenchymal transition (EMT) process, resulting in loss of cell migration and invasion ability. The small molecule NG52 dose-dependently inhibited the proliferation of ovarian cancer cells. In addition, NG52 reduced the EMT process and reversed the Warburg effect by inhibiting PGK1 activity. Therefore, PGK1 is an attractive molecular target for anti-glycolytic therapy of ovarian cancer.

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