Prevalence of ERG expression and PTEN loss in a Brazilian prostate cancer cohort

Morais, Carlos Eduardo Lima de; Gurgel, Daniel Cordeiro; Teixeira, André Costa; Mattos, T.V. Arruda; Silva, A.V. Alves da; Távora, Fábio

doi:10.1590/1414-431x20198483

Cited by 8 publications

(8 citation statements)

References 30 publications

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“…PTEN (Phosphatase and Tensin Homolog) belongs to the phosphatase group that regulates the signaling pathway of PI3K as well as AKT [64]; PTEN has tumor suppressor activity and is generally found idle connected to PCa [65]. Downregulated PTEN expression in our findings goes in line with the previously reported results in Iranian PCa patients [66].…”

Section: Discussionsupporting

confidence: 91%

Identification of Potential Key Genes in Prostate Cancer with Gene Expression, Pivotal Pathways and Regulatory Networks Analysis Using Integrated Bioinformatics Methods

Khan

Mohsen

Malik

et al. 2022

Genes

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Prostate cancer (PCa) is the most prevalent cancer (20%) in males and is accountable for a fifth (6.8%) cancer-related deaths in males globally. Smoking, obesity, race/ethnicity, diet, age, chemicals and radiation exposure, sexually transmitted diseases, etc. are among the most common risk factors for PCa. However, the basic change at the molecular level is the manifested confirmation of PCa. Thus, this study aims to evaluate the molecular signature for PCa in comparison to benign prostatic hyperplasia (BPH). Additionally, representation of differentially expressed genes (DEGs) are conducted with the help of some bioinformatics tools like DAVID, STRING, GEPIA, Cytoscape. The gene expression profile for the four data sets GSE55945, GSE104749, GSE46602, and GSE32571 was downloaded from NCBI, Gene Expression Omnibus (GEO). For the extracted DEGs, different types of analysis including functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction, survival analysis and transcription factor (TF) prediction were conducted. We obtained 633 most significant upregulated genes and 1219 downregulated genes, and a sum total of 1852 DEGs were found from all four datasets after assessment. The key genes, including EGFR, MYC, VEGFA, and PTEN, are targeted by TF such as AR, Sp1, TP53, NF-KB1, STAT3, RELA. Moreover, miR-21-5p also found significantly associated with all the four key genes. Further, The Cancer Genome Atlas data (TCGA) independent database was used for validation of key genes EGFR, MYC, VEGFA, PTEN expression in prostate adenocarcinoma. All four key genes were found to be significantly correlated with overall survival in PCa. Therefore, the therapeutic target may be determined by the information of these key gene’s findings for the diagnosis, prognosis and treatment of PCa.

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Section: Discussionsupporting

confidence: 91%

Identification of Potential Key Genes in Prostate Cancer with Gene Expression, Pivotal Pathways and Regulatory Networks Analysis Using Integrated Bioinformatics Methods

Khan

Mohsen

Malik

et al. 2022

Genes

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“… 6 Genomic characterization studies have demonstrated that 18%–70% of ductal adenocarcinomas have genetic alterations related to the PI3K pathway 6 , 7 , 8 , 9 ; this is consistent with the frequency of alterations in this study (33.3%). Although the reported incidence of PTEN alterations in East Asian patients with prostate cancer ranges from 10%–34%, which is lower than that in the United States and Western Europe (18%–40%), 24 , 25 , 26 the results of this study suggest that East Asians patients with ductal adenocarcinoma may have PTEN alterations at a similar frequency.…”

Section: Discussioncontrasting

confidence: 65%

Genomic analysis of aggressive ductal adenocarcinoma of the prostate

et al. 2022

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Background Genomic profile analysis using next‐generation sequencing can potentially elucidate the pathogenesis of rare cancers. Ductal adenocarcinoma, a rare subtype of prostate cancer, has an aggressive nature. This is the first study to analyze the genomic profile of ductal adenocarcinoma in an Asian population. Methods We identified 12 patients newly diagnosed with ductal adenocarcinoma of the prostate at two hospitals, and nine patients (75.0%) had the pure type. Genomic assessment was performed using either the PleSSision testing platform or FoundationOne CDx. Results At least one genomic alteration occurred in 11 patients (91.7%), and the most frequently mutated gene was tumor suppressor protein p53 (TP53), which was found in six cases (50.0%). Alterations characteristic of this cohort were found in four cases (33.3%) of retinoblastoma transcriptional corepressor 1 (RB1), which was only observed in the pure type. Compared to previous study results, the frequency of genetic alterations in the phosphoinositide 3‐kinase (PI3K) pathway (n = 3; 25.0%) and Wnt‐β‐catenin pathway (n = 5; 41.7%) was comparable, but no alterations in the DNA damage repair (DDR) pathway were observed. None of the patients presented high tumor mutation burden or microsatellite instability. Conclusions We found that the Asian cohort with ductal adenocarcinoma had actionable alterations, and a high frequency of alterations in TP53 and RB1 reflected the aggressive nature of the tumor. Genetic analysis using next‐generation sequencing is expected to help elucidate the pathogenesis of ductal adenocarcinoma.

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“…and A.C.L) independently who were initially blinded to the clinicopathological data of the patients as well as to each other’s results. After a literature review [ 29 ], a tissue specimen was considered to have PTEN protein loss if the intensity of cytoplasmic and nuclear staining was noticeably reduced or completely negative across >10% of tumor cells in relation to the surrounding benign glands or stroma, which were used as internal positive controls. In cases where PTEN was lost in >10 and <100% of the tumor cells, the specimen was considered to have heterogeneous PTEN loss (score 1).…”

Section: Methodsmentioning

confidence: 99%

Correlations of PTEN and ERG Immunoexpression in Prostate Carcinoma and Lesions Related to Its Natural History: Clinical Perspectives

Voulgari

Goutas

Pergaris

et al. 2023

CIMB

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Purpose: The aim of our study was to observe the associations between the ETS-related gene (ERG) and the phosphatase and tensin homolog gene (PTEN) immunoexpression in prostate cancer and related lesions and highlight the clinical significance of these findings. Methods: We evaluated the immunohistochemical expression of ERG and PTEN in a series of 151 invasive prostate adenocarcinomas, including low-grade (Gleason grade pattern 3) and high-grade (Gleason grade patterns 4, 5) morphological patterns which corresponded to 45.5% and 54.4% of the cases, respectively. Additionally, we evaluated the immunoexpression of the two markers both in foci of high-grade prostatic intraepithelial neoplasia (HGPIN), as a precursor lesion of cancer, and in foci of intraductal carcinoma of the prostate (IDCP). Finally, to ensure the malignant nature of the prostate glands examined, we employed p63 and alpha-methylacyl-CoA racemase (AMACR) expression. Results: We found that PTEN loss was observed in 50.7%, and ERG positivity was detected in 41.8% of our cancerous samples. In HGPIN, PTEN loss appeared to be linked with a high-grade adjacent invasive carcinoma component which also displayed PTEN loss. As far as IDCP is concerned, ERG immunonegativity was correlated with adjacent high-grade invasive cancer, which was also ERG immunonegative. Conclusions: Our findings suggest that the clonal expansion of invasive cancer appears to be associated with distinct immunophenotypic cellular alterations of both early and late cancer-related histological lesions. Patients with PTEN loss in HGPIN in prostate biopsies should be closely monitored due to the increased likelihood of having an associated invasive high-grade carcinoma that may have not been sampled. Given the clinical significance that derives from PTEN expression in HGPIN lesions, we suggest the routine use of PTEN immunohistochemistry in prostate cancer biopsies in which HGPIN is the only finding.

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Prevalence of ERG expression and PTEN loss in a Brazilian prostate cancer cohort

Cited by 8 publications

References 30 publications

Identification of Potential Key Genes in Prostate Cancer with Gene Expression, Pivotal Pathways and Regulatory Networks Analysis Using Integrated Bioinformatics Methods

Identification of Potential Key Genes in Prostate Cancer with Gene Expression, Pivotal Pathways and Regulatory Networks Analysis Using Integrated Bioinformatics Methods

Genomic analysis of aggressive ductal adenocarcinoma of the prostate

Correlations of PTEN and ERG Immunoexpression in Prostate Carcinoma and Lesions Related to Its Natural History: Clinical Perspectives

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