Despite multiple advances in the management of retinoblastoma, enucleation remains an essential therapeutic modality. We studied patients who underwent enucleation at the King Hussein Cancer Center in Jordan. We retrospectively reviewed medical records of children with retinoblastoma who were treated at our center from June 2002 to February 2008. Twenty-eight eyes from 27 patients were enucleated. Median age at diagnosis was 1.1 years (range, 0.3-6.3 years). Twenty-six eyes (93%) had advanced disease (RE groups IV and V). Seventeen patients (61%) had unilateral retinoblastoma, and 11 (39%) had bilateral retinoblastoma. The median time from diagnosis to enucleation was 0.45 months (range, 0-45 months; mean, 4.4 months) and was longer for patients with bilateral retinoblastoma (median, 2.2 vs. 0.2 months; P = 0.034). Twenty enucleated eyes (71%) did not show high-risk pathologic features. Seventeen eyes with advanced intraocular disease were enucleated at the time of presentation, whereas chemoreduction was attempted for the other 19 eyes with advanced intraocular disease. Enucleation was then recommended for nine (47%) of those eyes. Enucleation at the time of diagnosis was feasible for most patients with advanced disease. Attempted salvage of eyes with advanced disease is justified, particularly in patients with bilateral disease. We were able to salvage almost half of these eyes. We hope our study provides new insights for counseling patients.
Introduction: Triple-negative breast cancer (TNBC) is an aggressive type that lacks targeted therapies posing a challenge in its management. This necessitates identifying novel targets that may play a role in the regulation and progression of TNBC. There is renewed interest in targeting the androgen receptor (AR) since it is expressed in TNBC and plays an important role in its biology. Studies have shown that AR can influence the behavior of TNBC via affecting the of expression microRNA molecules (miRNAs), which can modulate the expression of cancer-regulatory proteins. We aimed to profile the expression of miRNAs in human TNBC tissue samples in relation to the expression of AR and investigate their prognostic value. Methods: The expression of 84 miRNAs in 24 TNBC tissue samples (12 AR-positive and 12 AR-negative) was examined using PCR array technology. Several bioinformatics tools were then utilized on the differentially expressed miRNAs (DE-miRNA) to determine the potentially affected protein targets and signaling pathways. Potential target genes (DEGs) for each miRNA were identified by miRWalk2.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for the target genes using the DAVID 6.8 bioinformatics tool. String and Cytoscape were used for establishing a PPI network and identifying the hub genes. Jamovi2.2 was used for the statistical analysis. Results: A total of 7 DE-miRNAs were found to be significantly expressed in the tissue samples relative to AR expression. Good and poor survival outcomes, respectively, were found to be linked to miR-328-3p and miR-489-3p. Interestingly, these two miRNAs were found to be up-regulated in AR-positive tumors. The association of miR-328-3p with AR corroborates our previous findings that this miRNA is up-regulated upon AR activation in TNBC cells. Two other miRNAs, miR-17-5p and iR-193b-3p, were found to be significantly associated with high T3 and low N2 status, respectively. Gene Ontology (GO) analysis for the 7 DE-miRNAs indicated a role in the regulation of the cell cycle in various cellular components (CC) such as the “nucleus”, “centrosome”, and “transcription factor complex”. GO analysis also showed enrichment in kinase and transcription factor activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses retrieved numerous relevant signaling pathways such as that of the TGF-beta, MAPK, Th17 cell differentiation, and endocrine resistance. Conclusion: This study offers an understanding of the molecular etiology of TNBC and further implicates miRNAs in mediating the effect of AR on TNBC. We also provide an integrative analysis of the AR-miRNA-TNBC gene network that can help in identifying potential therapeutic targets. Keywords: Breast Cancer, TNBC, Bioinformatics, miRNA, Androgen Receptor Citation Format: Bayan O. Abu Alragheb, Hassan Abushukair, Maysa Al-Husseini, Randa Bawadi, Mamoun Ahram. The association of androgen receptor with microRNA expression in triple-negative breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3772.
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