Sex-Specific Differences in Glioblastoma

Carrano, Anna; Juarez, Juan Jose; Incontri‐Abraham, Diego; Ibarra, Antonio; Guerrero-Cázares, Hugo

doi:10.3390/cells10071783

Cited by 100 publications

(51 citation statements)

References 145 publications

(225 reference statements)

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“…Moreover, nine of top ten candidate drugs were predicted to bind to PGR and eight were predicted to bind to Androgen Receptor (AR) (Additional file 1 : Figure S5E). Both of PGR and AR have been reported to play important roles in glioma [ 40 – 42 ].…”

Section: Resultsmentioning

confidence: 99%

From GWAS to drug screening: repurposing antipsychotics for glioblastoma

et al. 2022

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Background Glioblastoma is currently an incurable cancer. Genome-wide association studies have demonstrated that 41 genetic variants are associated with glioblastoma and may provide an option for drug development. Methods We investigated FDA-approved antipsychotics for their potential treatment of glioblastoma based on genome-wide association studies data using a ‘pathway/gene-set analysis’ approach. Results The in-silico screening led to the discovery of 12 candidate drugs. DepMap portal revealed that 42 glioma cell lines show higher sensitivities to 12 candidate drugs than to Temozolomide, the current standard treatment for glioblastoma. Conclusion In particular, cell lines showed significantly higher sensitivities to Norcyclobenzaprine and Protriptyline which were predicted to bind targets to disrupt a certain molecular function such as DNA repair, response to hormones, or DNA-templated transcription, and may lead to an effect on survival-related pathways including cell cycle arrest, response to ER stress, glucose transport, and regulation of autophagy. However, it is recommended that their mechanism of action and efficacy are further determined.

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Section: Resultsmentioning

confidence: 99%

From GWAS to drug screening: repurposing antipsychotics for glioblastoma

et al. 2022

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“…Our pipeline identified two clusters (G 1 and G 2 , Figure 1 a) by analyzing GBM editomes. The prognostic value of editing-based subtyping was evaluated in males and females separately since multiple lines of evidence have shown sex differences in GBM incidence and survival [ 50 , 51 ]. Intriguingly, samples in the same cluster exhibited sex dimorphism in survival.…”

Section: Resultsmentioning

confidence: 99%

“…We observed that editing profiles had sexually dimorphic prognostic values. Sex differences in incidence, disease phenotype, and clinical outcome have been well documented in GBM [ 50 , 91 , 92 ], but little is known about IDH-MUT gliomas. Moreover, the molecular differences that drive such different presentation and outcomes between sexes remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation Pathways

Lin

Chen

2022

Cells

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RNA editing alters the nucleotide sequence and has been associated with cancer progression. However, little is known about its prognostic and regulatory roles in glioma, one of the most common types of primary brain tumors. We characterized and analyzed RNA editomes of glioblastoma and isocitrate dehydrogenase mutated (IDH-MUT) gliomas from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas (CGGA). We showed that editing change during glioma progression was another layer of molecular alterations and that editing profiles predicted the prognosis of glioblastoma and IDH-MUT gliomas in a sex-dependent manner. Hyper-editing was associated with poor survival in females but better survival in males. Moreover, noncoding editing events impacted mRNA abundance of the host genes. Genes associated with inflammatory response (e.g., EIF2AK2, a key mediator of innate immunity) and fatty acid oxidation (e.g., acyl-CoA oxidase 1, the rate-limiting enzyme in fatty acid β-oxidation) were editing-regulated and associated with glioma progression. The above findings were further validated in CGGA samples. Establishment of the prognostic and regulatory roles of RNA editing in glioma holds promise for developing editing-based therapeutic strategies against glioma progression. Furthermore, sexual dimorphism at the epitranscriptional level highlights the importance of developing sex-specific treatments for glioma.

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“…Sex differences have been well identified in many brain tumors including glioma. The sex-specific effects for the incidence, phenotype, and outcome of glioma have been well described; however, few insights are available to distinguish male and female glioma patients at the molecular level or allow specific targeting of these biological differences ( 30 , 31 ). More studies are needed to focus on sex differences in GBM in terms of pathophysiology, hormones, metabolism, tumor location, treatment response, recurrence, and outcome ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

MAPK Activated Protein Kinase 3 Is a Prognostic-Related Biomarker and Associated With Immune Infiltrates in Glioma

Ren

Sun

et al. 2021

Front. Oncol.

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Glioma is the most common primary brain tumor that causes significant morbidity and mortality. MAPK activated protein kinase 3 (MAPKAPK3/MK3) is a serine/threonine protein kinase regulating various cellular responses and gene expression. However, the role of MK3 in tumor progress, prognosis, and immunity for glioma remains unclear. Here, we determined the expression and prognostic values of MK3. We further analyzed the correlation of MK3 expression with immune infiltrations by using the biochemical methods and bioinformatic approaches with available databases. We find that MK3 is aberrantly upregulated in glioma. In addition, the higher MK3 expression is closely linked to the poor clinicopathologic features of glioma patients. Importantly, MK3 expression is negatively correlated with the prognosis of patients with glioma. Mechanistically, we demonstrated that the correlated genes of MK3 were mainly enriched in pathways that regulate tumor immune responses. The MK3 level was significantly associated with tumor-infiltrating immune cells and positively correlated with the majority of tumor immunoinhibitors, chemokines, and chemokine receptors in glioma. Thus, these findings suggest the novel prognostic roles of MK3 and define MK3 as a promising target for glioma immunotherapy.

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Sex-Specific Differences in Glioblastoma

Cited by 100 publications

References 145 publications

From GWAS to drug screening: repurposing antipsychotics for glioblastoma

From GWAS to drug screening: repurposing antipsychotics for glioblastoma

RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation Pathways

MAPK Activated Protein Kinase 3 Is a Prognostic-Related Biomarker and Associated With Immune Infiltrates in Glioma

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