Computational analysis of TP53 vs. CTNNB1 mutations in hepatocellular carcinoma suggests distinct cancer subtypes with differential gene expression profiles and chromatin states.

Genetic variations are important drivers of carcinogenesis. It is extremely important to identify molecular distinctions between patients of the same disease for effective cancer treatment. This study aims to understand cellular and molecular differences between hepatocellular carcinoma patients carrying TP53 or CTNNB1 mutations, which could possess clinical significance. For this purpose, DNA sequencing and mRNA expression data for hepatocellular carcinoma patients were analyzed. Differentially expressed genes and the cellular processes that they are involved in were determined for TP53/CTNNB1-altered patient groups. We found that the mutations of TP53/CTNNB1 genes in the patient cohort was almost mutually exclusive and gene expression profiling in these subgroups were unique. Gene Ontology (GO) enrichment analysis of the differentially expressed genes identified several important cellular processes. In line with this, selected histone variants, histone chaperons, as well as the binding partners of TP53/CTNNB1 showed distinct enrichment levels. TP53/CTNNB1-altered patient groups laso showed different prognostic outcomes and tumor infiltration levels. In conclusion, our results strongly imply differential chromatin states and transcriptional regulation in relation to the mutational status of TP53 vs. CTNNB1, suggesting that these genes might be inducing different cellular pathways involving distinct chromatin environments during the course of carcinogenesis.

Molecular profiling of immune cell-enriched Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacting protein USP13.

AIMS: Coronavirus disease 2019 (COVID-19), which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a major health concern worldwide. Due to the lack of specific medication and vaccination, drug-repurposing attempts has emerged as a promising approach and identified several human proteins interacting with the virus. This study aims to provide a comprehensive molecular profiling of the immune cell-enriched SARS-CoV-2 interacting protein USP13. MATERIALS AND METHODS: The list of immune cell-enriched proteins interacting with SARS-CoV-2 was retrieved from The Human Protein Atlas. Genomic alterations were identified using cBioPortal. Survival analysis was performed via Kaplan-Meier Plotter. Analyses of protein expression and tumor infiltration levels were carried out by TIMER. KEY FINDINGS: 14 human proteins that interact with SARS-CoV-2 were enriched in immune cells. Among these proteins, USP13 had the highest frequency of genomic alterations. Higher USP13 levels were correlated with improved survival in breast and lung cancers, while resulting in poor prognosis in ovarian and gastric cancers. Furthermore, copy number variations of USP13 significantly affected the infiltration levels of distinct subtypes of immune cells in head & neck, lung, ovarian and stomach cancers. Although our results suggested a tumor suppressor role for USP13 in lung cancer, in other cancers, its role seemed to be context-dependent. SIGNIFICANCE: It is critical to identify and characterize human proteins that interact with SARS-CoV-2 in order to have a better understanding of the disease and to develop better therapies/vaccines. Here, we provided a comprehensive molecular profiling the immune cell-enriched SARS-CoV-2 interacting protein USP13, which will be useful for future studies.

A comprehensive analysis of the angiogenesis-related genes in glioblastoma multiforme vs. brain lower grade glioma.

OBJECTIVE: Brain tumors are one of the most common causes of cancer-related deaths around the world. Angiogenesis is critical in high-grade malignant gliomas, such as glioblastoma multiforme. The aim of this study is to comparatively analyze the angiogenesis-related genes, namely VEGFA, VEGFB, KDR, CXCL8, CXCR1 and CXCR2 in LGG vs. GBM to identify molecular distinctions using datasets available on The Cancer Genome Atlas (TCGA). METHODS: DNA sequencing and mRNA expression data for 514 brain lower grade glioma (LGG) and 592 glioblastoma multiforme (GBM) patients were acquired from The Cancer Genome Atlas (TCGA), and the genetic alterations and expression levels of the selected genes were analyzed. RESULTS: We identified six distinct KDR mutations in the LGG patients and 18 distinct KDR mutations in the GBM patients, including missense and nonsense mutations, frame shift deletion and altered splice region. Furthermore, VEGFA and CXCL8 were significantly overexpressed within GBM patients. CONCLUSIONS: VEGFA and CXCL8 are important factors for angiogenesis, which are suggested to have significant roles during tumorigenesis. Our results provide further evidence that VEGFA and CXCL8 could induce angiogenesis and promote LGG to progress into GBM. These findings could be useful in developing novel targeted therapeutics approaches in the future.

Data article on genes that share similar expression patterns with EEF1 complex proteins in hepatocellular carcinoma.

Eukaryotic Elongation Factor complex 1 (EEF1) consists of six subunits namely EEF1A1, EEF1A2, EEF1B2, EEF1D, EEF1E1 and EEF1G. Recently we showed that EEF1 complex proteins might play critical roles in cancer [1]. This article provides data on genes that share similar expression patterns with EEF1 complex proteins in cancer by analyzing RNA expression data using GEPIA online tool. Correlation analysis was performed on selected genes in a pairwise manner and the Pearson coefficients were automatically calculated by the GEPIA online tool. These data can be useful for future studies directed towards understanding the mechanisms by which EEF1 complex proteins affect in cancer pathogenesis.

A comprehensive analysis of the angiogenesis-related genes in glioblastoma multiforme vs. brain lower grade glioma / Uma análise abrangente dos genes relacionados à angiogênese no glioblastoma multiforme vs. glioma cerebral de baixo grau

Abstract Brain tumors are one of the most common causes of cancer-related deaths around the world. Angiogenesis is critical in high-grade malignant gliomas, such as glioblastoma multiforme. Objective: The aim of this study is to comparatively analyze the angiogenesis-related genes, namely VEGFA, VEGFB, KDR, CXCL8, CXCR1 and CXCR2 in LGG vs. GBM to identify molecular distinctions using datasets available on The Cancer Genome Atlas (TCGA). Methods: DNA sequencing and mRNA expression data for 514 brain lower grade glioma (LGG) and 592 glioblastoma multiforme (GBM) patients were acquired from The Cancer Genome Atlas (TCGA), and the genetic alterations and expression levels of the selected genes were analyzed. Results: We identified six distinct KDR mutations in the LGG patients and 18 distinct KDR mutations in the GBM patients, including missense and nonsense mutations, frame shift deletion and altered splice region. Furthermore, VEGFA and CXCL8 were significantly overexpressed within GBM patients. Conclusions: VEGFA and CXCL8 are important factors for angiogenesis, which are suggested to have significant roles during tumorigenesis. Our results provide further evidence that VEGFA and CXCL8 could induce angiogenesis and promote LGG to progress into GBM. These findings could be useful in developing novel targeted therapeutics approaches in the future.

Resumo Os tumores cerebrais são uma das causas mais comuns de mortes relacionadas ao câncer em todo o mundo. A angiogênese tem caráter crítico em gliomas malignos de alto grau, como o glioblastoma multiforme. Objetivo: O objetivo deste estudo foi analisar comparativamente os genes relacionados à angiogênese, VEGFA, VEGFB, KDR, CXCL8, CXCR1 e CXCR2 em GBG vs. GBM para identificar distinções moleculares usando conjuntos de dados disponíveis no The Cancer Genome Atlas (TCGA). Métodos: Os dados de sequenciamento de DNA e expressão de mRNA para 514 pacientes com glioma cerebral de baixo grau (GBG) e 592 pacientes com glioblastoma multiforme (GBM) foram adquiridos do TCGA e as alterações genéticas e os níveis de expressão dos genes selecionados foram analisados. Resultados: Identificamos seis mutações KDR distintas nos pacientes GBG e 18 mutações KDR distintas nos pacientes GBM, incluindo mutações missense e nonsense, exclusão de mudança de quadro e região de emenda alterada. Além disso, VEGFA e CXCL8 foram significativamente super-expressos nos pacientes com GBM. Conclusões: VEGFA e CXCL8 são fatores importantes para a angiogênese, os quais parecem ter um papel significativo durante a tumorigênese. Nossos resultados fornecem evidências adicionais de que o VEGFA e o CXCL8 podem induzir a angiogênese e promover o GBG a progredir no GBM. Esses achados podem ser úteis no desenvolvimento de novas abordagens terapêuticas direcionadas no futuro.

Alterations in Eukaryotic Elongation Factor complex proteins (EEF1s) in cancer and their implications in epigenetic regulation.

AIMS: In the cell, both transcriptional and translational processes are tightly regulated. Cancer is a multifactorial disease characterized by aberrant protein expression. Since epigenetic control mechanisms are also frequently disrupted during carcinogenesis, they have been the center of attention in cancer research within the past decades. EEF1 complex members, which are required for the elongation process in eukaryotes, have recently been implicated in carcinogenesis. This study aims to investigate genetic alterations within EEF1A1, EEF1A2, EEF1B2, EEF1D, EEF1E1 and EEF1G genes and their potential effects on epigenetic regulation mechanisms. MATERIALS AND METHODS: In this study, we analyzed DNA sequencing and mRNA expression data available on The Cancer Genome Atlas (TCGA) across different cancer types to detect genetic alterations in EEF1 genes and investigated their potential impact on selected epigenetic modulators. KEY FINDINGS: We found that EEF1 complex proteins were deregulated in several types of cancer. Lower EEF1A1, EEF1B2, EEF1D and EEF1G levels were correlated with poor survival in glioma, while lower EEF1B2, EEF1D and EEF1E1 levels were correlated with better survival in hepatocellular carcinoma. We detected genetic alterations within EEF1 genes in up to 35% of the patients and showed that these alterations resulted in down-regulation of histone modifying enzymes KMT2C, KMT2D, KMT2E, KAT6A and EP300. SIGNIFICANCE: Here in this study, we showed that EEF1 deregulations might result in differential epigenomic landscapes, which affect the overall transcriptional profile, contributing to carcinogenesis. Identification of these molecular distinctions might be useful in developing targeted drug therapies and personalized medicine.