The ETS Homologous Factor (EHF) Represents a Useful Immunohistochemical Marker for Predicting Prostate Cancer Metastasis

Scimeca, Manuel; Montanaro, Manuela; Bonfiglio, Rita; Anemona, Lucia; Agrò, Enrico Finazzi; Asimakopoulos, Anastasios D.; Bei, Roberto; Manzari, Vittorio; Urbano, Nicoletta; Giacobbi, Erica; Servadei, Francesca; Bonanno, Elena; Schillaci, Orazio; Mauriello, Alessandro

doi:10.3390/diagnostics12040800

Cited by 5 publications

(5 citation statements)

References 37 publications

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“…3D) 60,63 . Further, CBP was enriched for PCa-associated transcription factors, including ETS-factor, Elk4 and SP1 62,64,67–70 . Conversely, in addition to FOXA1, p300 was enriched for mitochondrial factor (GFY), zinc finger proteins (Bc111a, ZNF143), and PCa- associated transcription factors (HOXB13) 71–78 .…”

Section: Resultsmentioning

confidence: 99%

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AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer

Sardar,

McNair,

Ravindranath

et al. 2024

Preprint

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Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease. CBP/p300 bromodomain inhibition enhances response to standard of care therapeutics. Functional studies, CBP/p300 cistrome mapping, and transcriptome in CRPC revealed that CBP/p300 regulates DDR. Further mechanistic investigation showed that CBP/p300 attenuation via therapeutic targeting and genomic knockdown decreases homologous recombination (HR) factorsin vitro,in vivo, and in human prostate cancer (PCa) tumorsex vivo. Similarly, CBP/p300 expression in human prostate tissue correlates with HR factors. Lastly, targeting CBP/p300 impacts HR-mediate repair and patient outcome. Collectively, these studies identify CBP/p300 as drivers of PCa tumorigenesis and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed and DDR therapies.

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Section: Resultsmentioning

confidence: 99%

“…3D). Proximal to CBP binding, motifs are enriched for Ets-factors Elk4 and Sp1, which are linked to PCa oncogenic signaling 62,64,67–70 . Intriguingly, proximal to p300 binding, motifs are enriched for GFY, ZNF143, and HOXB13, which are linked to mitochondrial signaling and zinc-finger function 71–78 .…”

Section: Discussionmentioning

confidence: 99%

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer

Sardar,

McNair,

Ravindranath

et al. 2024

Preprint

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“…Numerous studies highlight the implication of microRNAs (miRNAs) in cancer research, as they play an important role in regulating cancer cells and impacting various aspects of cancer progression, including apoptosis induction, cell cycle regulation, metastasis promotion, and angiogenesis stimulation [30,[62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. In a recent investigation by Xiong et al [79], the effects of circSETD3, a circular RNA containing multiple miRNA binding sites, were studied in CCA cells.…”

Section: Potential Therapeutical Approachesmentioning

confidence: 99%

Programmed Cell Death Pathways in Cholangiocarcinoma: Opportunities for Targeted Therapy

Scimeca

Rovella

Palumbo

et al. 2023

Cancers

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Cholangiocarcinoma is a highly aggressive cancer arising from the bile ducts. The limited effectiveness of conventional therapies has prompted the search for new approaches to target this disease. Recent evidence suggests that distinct programmed cell death mechanisms, namely, apoptosis, ferroptosis, pyroptosis and necroptosis, play a critical role in the development and progression of cholangiocarcinoma. This review aims to summarize the current knowledge on the role of programmed cell death in cholangiocarcinoma and its potential implications for the development of novel therapies. Several studies have shown that the dysregulation of apoptotic signaling pathways contributes to cholangiocarcinoma tumorigenesis and resistance to treatment. Similarly, ferroptosis, pyroptosis and necroptosis, which are pro-inflammatory forms of cell death, have been implicated in promoting immune cell recruitment and activation, thus enhancing the antitumor immune response. Moreover, recent studies have suggested that targeting cell death pathways could sensitize cholangiocarcinoma cells to chemotherapy and immunotherapy. In conclusion, programmed cell death represents a relevant molecular mechanism of pathogenesis in cholangiocarcinoma, and further research is needed to fully elucidate the underlying details and possibly identify therapeutic strategies.

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“…The Gleason score (GS) is the most widely used tool to assess the aggressiveness of PCa [ 3 – 5 ]. Studies have reported that the number of positive needles of systematic biopsy is also one of the indicators for assessing PCa aggressiveness [ 6 ]. A considerable difference in prognosis exists between patients with ≥ 50% positive needles and those with < 50% positive needles [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Prediction of prostate cancer aggressiveness using magnetic resonance imaging radiomics: a dual-center study

Pan,

Shi,

et al. 2024

Discov Onc

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Purpose The Gleason score (GS) and positive needles are crucial aggressive indicators of prostate cancer (PCa). This study aimed to investigate the usefulness of magnetic resonance imaging (MRI) radiomics models in predicting GS and positive needles of systematic biopsy in PCa. Material and Methods A total of 218 patients with pathologically proven PCa were retrospectively recruited from 2 centers. Small-field-of-view high-resolution T2-weighted imaging and post-contrast delayed sequences were selected to extract radiomics features. Then, analysis of variance and recursive feature elimination were applied to remove redundant features. Radiomics models for predicting GS and positive needles were constructed based on MRI and various classifiers, including support vector machine, linear discriminant analysis, logistic regression (LR), and LR using the least absolute shrinkage and selection operator. The models were evaluated with the area under the curve (AUC) of the receiver-operating characteristic. Results The 11 features were chosen as the primary feature subset for the GS prediction, whereas the 5 features were chosen for positive needle prediction. LR was chosen as classifier to construct the radiomics models. For GS prediction, the AUC of the radiomics models was 0.811, 0.814, and 0.717 in the training, internal validation, and external validation sets, respectively. For positive needle prediction, the AUC was 0.806, 0.811, and 0.791 in the training, internal validation, and external validation sets, respectively. Conclusions MRI radiomics models are suitable for predicting GS and positive needles of systematic biopsy in PCa. The models can be used to identify aggressive PCa using a noninvasive, repeatable, and accurate diagnostic method.

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The ETS Homologous Factor (EHF) Represents a Useful Immunohistochemical Marker for Predicting Prostate Cancer Metastasis

Cited by 5 publications

References 37 publications

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer

Programmed Cell Death Pathways in Cholangiocarcinoma: Opportunities for Targeted Therapy

Prediction of prostate cancer aggressiveness using magnetic resonance imaging radiomics: a dual-center study

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