Experimental challenges to modeling prostate cancer heterogeneity

Flores-Téllez, Teresita del N.J.; Baena, Esther

doi:10.1016/j.canlet.2021.10.012

Cited by 14 publications

(5 citation statements)

References 147 publications

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“…It is important to realize that the overall tumour expression of miR-21 and RHOB will be determined by a variety of cell types, such as immune cells and fibroblasts, as well as tumour cells. Likewise, there may be multiple tumour foci present, representing tumour cells with distinctly different molecular characteristics, which provides significant challenges for modelling the disease in experiments [102]. Future work to address this is likely to require single-cell analyses coupled with advanced proteomics to gain further insight into the intra-tumour and inter-tumour heterogeneity present in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

MiR-21 Is Induced by Hypoxia and Down-Regulates RHOB in Prostate Cancer

Angel

Stafford

McNally

et al. 2023

Cancers

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Tumour hypoxia is a well-established contributor to prostate cancer progression and is also known to alter the expression of several microRNAs. The over-expression of microRNA-21 (miR-21) has been consistently linked with many cancers, but its role in the hypoxic prostate tumour environment has not been well studied. In this paper, the link between hypoxia and miR-21 in prostate cancer is investigated. A bioinformatic analysis of The Cancer Genome Atlas (TCGA) prostate biopsy datasets shows the up-regulation of miR-21 is significantly associated with prostate cancer and clinical markers of disease progression. This up-regulation of miR-21 expression was shown to be caused by hypoxia in the LNCaP prostate cancer cell line in vitro and in an in vivo prostate tumour xenograft model. A functional enrichment analysis also revealed a significant association of miR-21 and its target genes with processes related to cellular hypoxia. The over-expression of miR-21 increased the migration and colony-forming ability of RWPE-1 normal prostate cells. In vitro and in silico analyses demonstrated that miR-21 down-regulates the tumour suppressor gene Ras Homolog Family Member B (RHOB) in prostate cancer. Further a TCGA analysis illustrated that miR-21 can distinguish between different patient outcomes following therapy. This study presents evidence that hypoxia is a key contributor to the over-expression of miR-21 in prostate tumours, which can subsequently promote prostate cancer progression by suppressing RHOB expression. We propose that miR-21 has good potential as a clinically useful diagnostic and prognostic biomarker of hypoxia and prostate cancer.

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Section: Discussionmentioning

confidence: 99%

MiR-21 Is Induced by Hypoxia and Down-Regulates RHOB in Prostate Cancer

Angel

Stafford

McNally

et al. 2023

Cancers

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“…PCa is characterized by its significant heterogeneity, which implies a wide range of oncologic prognoses [ 27 , 28 ]. The majority of prostate cancers are slow-growing, but the remaining cases can be extremely aggressive and even fatal [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Prostate Region-Wise Imaging Biomarker Profiles for Risk Stratification and Biochemical Recurrence Prediction

Sánchez Iglesias,

Morillo Macías,

Picó Peris

et al. 2023

Cancers

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Background: Identifying prostate cancer (PCa) patients with a worse prognosis and a higher risk of biochemical recurrence (BCR) is essential to guide treatment choices. Here, we aimed to identify possible imaging biomarker (perfusion/diffusion + radiomic features) profiles extracted from MRIs that were able to discriminate patients according to their risk or the occurrence of BCR 10 years after diagnosis, as well as to evaluate their predictive value with or without clinical data. Methods: Patients with localized PCa receiving neoadjuvant androgen deprivation therapy and radiotherapy were retrospectively evaluated. Imaging features were extracted from MRIs for each prostate region or for the whole gland. Univariate and multivariate analyses were conducted. Results: 128 patients (mean [range] age, 71 [50–83] years) were included. Prostate region-wise imaging biomarker profiles mainly composed of radiomic features allowed discriminating risk groups and patients experiencing BCR. Heterogeneity-related radiomic features were increased in patients with worse prognosis and with BCR. Overall, imaging biomarkers profiles retained good predictive ability (AUC values superior to 0.725 in most cases), which generally improved when clinical data were included (particularly evident for the prediction of the BCR, with AUC values ranging from 0.841 to 0.877 for combined models and sensitivity values above 0.960) and when models were built per prostate region vs. the whole gland. Conclusions: Prostate region-aware imaging profiles enable identification of patients with worse prognosis and with a higher risk of BCR, retaining higher predictive values when combined with clinical variables.

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“…Prostate cancer is a highly heterogeneous entity, comprised of multiple cancer cell subpopulations (including CSCs) and non-tumoral cells such as epithelial cells, stromal cells, immune cells, vascular endothelial cells, tumor-associated macrophages (TAMs) and cancer associated fibroblasts [29][30][31]. Studies involving CSCs has progressed rapidly, and novel techniques for identification, purification, and characterization of these cells have been developed.…”

Section: Prostate Cancer Stem Cellsmentioning

confidence: 99%

Interaction between prostate cancer stem cells and bone microenvironment regulates prostate cancer bone metastasis and treatment resistance

Yao

Zhang

2022

J. Cancer

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Prostate cancer (PCa) is one of the most common cancers with increasing rates of incidence. Bone metastasis and drug resistance are the most serious threat faced by patients following a delayed diagnosis of cancer, which might lead to treatment failure and death. The theoretical model of cancer stem cells (CSCs) explains the diverse molecular characteristics of cancer as well as its relapse, metastasis and drug resistance. Prostate cancer involves heterogeneous cells community, including prostate cancer stem cells as an important component. These subtypes of cancer cells are usually monoclonal, expressing specific biomarkers and exhibiting self-renewal and differentiation capacity. Therefore, therapies that target CSCs might be more effective in overcome drug resistance and metastasis. Thus, anti-CSCs therapies differ from the traditional anti-proliferative approach. We focus here on reviewing the effects of prostate CSCs on bone metastasis and resistance to traditional treatment in PCa, and report new clinical strategies that address CSC-based tumorigenesis.

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Experimental challenges to modeling prostate cancer heterogeneity

Cited by 14 publications

References 147 publications

MiR-21 Is Induced by Hypoxia and Down-Regulates RHOB in Prostate Cancer

MiR-21 Is Induced by Hypoxia and Down-Regulates RHOB in Prostate Cancer

Prostate Region-Wise Imaging Biomarker Profiles for Risk Stratification and Biochemical Recurrence Prediction

Interaction between prostate cancer stem cells and bone microenvironment regulates prostate cancer bone metastasis and treatment resistance

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