Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical Carcinoma

Purpose of review comprehensive molecular characterization of adrenocortical carcinoma (ACC) through next-generation sequencing and bioinformatics analyses is expanding the number of targets with potential prognostic and therapeutic value. We performed a critical review of recent published literature on genotyping of ACC.Recent findings 423 studies were published between 2019 and 2021. After manual curation we summarized selected evidence in two thematic areas: germline deoxyribonucleic acid (DNA) variations, genomic alterations and prognosis. Summarythe evolving genomic landscape of ACC requires target validation in terms of prognostic and predictive value within scientific consortia. Although the existing multiple driver genes are difficult targets in the perspective of precision oncology, alterations in DNA damage repair genes or in promoter hypermethylation could open new venues for repurposing of existing drugs in ACC.

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“…In the predefined time frame, 29 original works were published and a summary is provided in Table 2[50,51 ▪ ,52 ▪ ,54–67,68 ▪ ,69–75].…”

Section: Systematic Analysis Of Literature 2019–2021 Of Molecular Gen...mentioning

confidence: 99%

Molecular genotyping of adrenocortical carcinoma: a systematic analysis of published literature 2019–2021

Grisanti

Cosentini

Sigala

et al. 2021

Current Opinion in Oncology

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“…A scatter diagram and paired plot were generated by the Wilcox test in R software. We followed the methods of [22] .…”

Section: Data Processing and Differentially Expressed Gene Analysismentioning

confidence: 99%

Identification of Potential Prognostic Biomarkers for Tongue Squamous Cell Carcinoma

Zhang

et al. 2020

Preprint

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Background: Tongue squamous cell carcinoma (TSCC) is one of the most common types of oral cancer and has a poor prognosis owing to a limited understanding of its pathogenetic mechanisms. The purpose of this study was to explore and identify potential biomarkers in TSCC by integrated bioinformatics analysis.Methods: The RNA sequencing data, methylation data, and clinical characteristics of TSCC patients were downloaded from The Cancer Genome Atlas (TCGA), and then differentially expressed RNAs (DERNAs), including differentially expressed long noncoding RNAs (DElncRNAs) and differentially expressed messenger RNAs (DEmRNAs), were identified in TSCC by bioinformatics analysis. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Hallmark pathway analyses were used to analyze the DERNAs. Univariate and multivariate Cox regression analyses were used to develop four-lncRNA and two-mRNA signatures and predict survival in TSCC patients. We established a risk model to predict the overall survival (OS) of TSCC patients based on the DERNAs with Kaplan–Meier analysis and the log-rank p test. Furthermore, weighted gene coexpression network analysis (WGCNA) was performed in Cytoscape, and a protein-protein interaction (PPI) network was established in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database.Results: A total of 2,006 DEmRNAs and 1,001 DElncRNAs were found to be dysregulated in TSCC. A total of 417 DERNAs were used to construct the coexpression network, and the PPI network included 103 DEmRNAs. Univariate regression analysis of the DERNAs revealed 51 DElncRNAs and 90 DEmRNAs that were associated with OS in TSCC patients. Multivariate Cox regression analysis demonstrated that four of those lncRNAs (MGC32805, RP1-35C21.2, RP11-108K3.1, and RP11-109M17.2) and two mRNAs (CA9, GTSF1L) had significant prognostic value, and their cumulative risk score indicated that these four-lncRNA and two-mRNA signatures independently predicted OS in TSCC patients. Additionally, there was a positive correlation between the expression and methylation level of RP11-108K3.1, the OS significantly negatively correlated with hypermethylation and low expression of GTSF1L along with hypomethylation and high expression of CA9.Conclusions: The current findings provide novel insights into the molecular mechanisms of TSCC and identify four lncRNAs and two mRNAs that are potential biomarkers that may be independent prognostic signatures for TSCC diagnosis and treatment.

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“…Among other genes differentially expressed between ACA and ACC, osteopontin and serine threonine kinase 15 were significantly up-regulated (up to 20-fold) in the latter group [ 17 ]. In addition, other differential molecular alterations between ACA and ACC were identified within the microRNA or long-non-coding RNA profiles, gene methylation status [ 22 , 23 , 24 ] or in the expression levels of single biomarkers, including livin/BIRC7 [ 25 ], NOTCH pathway [ 26 ] and CYP2W1 [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Differential Expression Profiles of Cell-to-Matrix-Related Molecules in Adrenal Cortical Tumors: Diagnostic and Prognostic Implications

Volante

Rapa

Metović

et al. 2021

JPM

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The molecular mechanisms of adrenocortical carcinoma development are incompletely defined. De-regulation of cellular-to-extracellular matrix interactions and angiogenesis appear among mechanisms associated to the malignant phenotype. Our aim was to investigate, employing PCR-based array profiling, 157 molecules involved in cell-to-matrix interactions and angiogenesis in a frozen series of 6 benign and 6 malignant adrenocortical neoplasms, to identify novel pathogenetic markers. In 14 genes, a significant dysregulation was detected in adrenocortical carcinomas as compared to adenomas, most of them being downregulated. Three exceptions—hyaluronan synthase 1 (HAS-1), laminin α3 and osteopontin genes—demonstrated an increased expression in adrenocortical carcinomas of 4.46, 4.23 and 20.32-fold, respectively, and were validated by immunohistochemistry on a series of paraffin-embedded tissues, including 20 adenomas and 73 carcinomas. Osteopontin protein, absent in all adenomas, was expressed in a carcinoma subset (25/73) (p = 0.0022). Laminin α3 and HAS-1 were mostly expressed in smooth muscle and endothelial cells of the vascular network of both benign and malignant adrenocortical tumors. HAS-1 was also detected in tumor cells, with a more intense pattern in carcinomas. In this group, strong expression was significantly associated with more favorable clinicopathological features. These data demonstrate that cell-to-matrix interactions are specifically altered in adrenocortical carcinoma and identify osteopontin and HAS-1 as novel potential diagnostic and prognostic biomarkers, respectively, in adrenal cortical tumors.

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Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical Carcinoma

Cited by 6 publications

References 48 publications

Molecular genotyping of adrenocortical carcinoma: a systematic analysis of published literature 2019–2021

Molecular genotyping of adrenocortical carcinoma: a systematic analysis of published literature 2019–2021

Identification of Potential Prognostic Biomarkers for Tongue Squamous Cell Carcinoma

Differential Expression Profiles of Cell-to-Matrix-Related Molecules in Adrenal Cortical Tumors: Diagnostic and Prognostic Implications

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