Comparative analysis of epi-miRNA expression levels in local/locally advanced and metastatic prostate cancer patients

Gurbuz, Venhar; Kılıçcıoğlu, İlker; Dikmen, Asiye Uğraş; Bilen, Cenk Yücel; Sözen, Sinan; Konac, Ece

doi:10.1016/j.gene.2020.144963

Cited by 10 publications

(9 citation statements)

References 40 publications

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“…From studies published so far, two include using plasma as a sample and one each using sera and whole blood. They all showed overexpression in PCa compared to healthy controls [ 36 , 37 , 38 , 39 ]. These studies included healthy men as controls, which might be a reason for different findings in our study.…”

Section: Discussionmentioning

confidence: 99%

MiR-182-5p and miR-375-3p Have Higher Performance Than PSA in Discriminating Prostate Cancer from Benign Prostate Hyperplasia

Abramović

Vrhovec

Škara

et al. 2021

Cancers

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Prostate cancer (PCa) is the most commonly diagnosed neoplasm among men. Since it often resembles benign prostate hyperplasia (BPH), biomarkers with a higher differential value than PSA are required. Epigenetic biomarkers in liquid biopsies, especially miRNA, could address this challenge. The absolute expression of miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were quantified in blood plasma and seminal plasma of 65 PCa and 58 BPH patients by digital droplet PCR. The sensitivity and specificity of these microRNAs were determined using ROC curve analysis. The higher expression of miR-182-5p and miR-375-3p in the blood plasma of PCa patients was statistically significant as compared to BPH (p = 0.0363 and 0.0226, respectively). Their combination achieved a specificity of 90.2% for predicting positive or negative biopsy results, while PSA cut-off of 4 µg/L performed with only 1.7% specificity. In seminal plasma, miR-375-3p, miR-182-5p, and miR-21-5p showed a statistically significantly higher expression in PCa patients with PSA >10 µg/L compared to ones with PSA ≤10 µg/L. MiR-182-5p and miR-375-3p in blood plasma show higher performance than PSA in discriminating PCa from BPH. Seminal plasma requires further investigation as it represents an obvious source for PCa biomarker identification.

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Section: Discussionmentioning

confidence: 99%

MiR-182-5p and miR-375-3p Have Higher Performance Than PSA in Discriminating Prostate Cancer from Benign Prostate Hyperplasia

Abramović

Vrhovec

Škara

et al. 2021

Cancers

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“…Nevertheless, the number of experimentally validated epi-miRNAs is still very low [124]. A recent study by Gurbuz et al [125] provided the first evidence of the combined effect of two epigenetic mechanisms, miRNA and DNA methylation, on PCa metastatic progression. Considering the methylation profiles, Gurbuz and colleagues identified 8 miRNAs, among 30 epi-miRNAs analyzed, which are promising biomarkers for the prediction of PCa progression.…”

Section: Epigenetic (Epi)-mirnasmentioning

confidence: 99%

Exploring miRNA Signature and Other Potential Biomarkers for Oligometastatic Prostate Cancer Characterization: The Biological Challenge behind Clinical Practice. A Narrative Review

Corrao

Zaffaroni

Bergamaschi

et al. 2021

Cancers

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In recent years, a growing interest has been directed towards oligometastatic prostate cancer (OMPC), as patients with three to five metastatic lesions have shown a significantly better survival as compared with those harboring a higher number of lesions. The efficacy of local ablative treatments directed on metastatic lesions (metastases-directed treatments) was extensively investigated, with the aim of preventing further disease progression and delaying the start of systemic androgen deprivation therapies. Definitive diagnosis of prostate cancer is traditionally based on histopathological analysis. Nevertheless, a bioptic sample—static in nature—inevitably fails to reflect the dynamics of the tumor and its biological response due to the dynamic selective pressure of cancer therapies, which can profoundly influence spatio-temporal heterogeneity. Furthermore, even with new imaging technologies allowing an increasingly early detection, the diagnosis of oligometastasis is currently based exclusively on radiological investigations. Given these premises, the development of minimally-invasive liquid biopsies was recently promoted and implemented as predictive biomarkers both for clinical decision-making at pre-treatment (baseline assessment) and for monitoring treatment response during the clinical course of the disease. Through liquid biopsy, different biomarkers, commonly extracted from blood, urine or saliva, can be characterized and implemented in clinical routine to select targeted therapies and assess treatment response. Moreover, this approach has the potential to act as a tissue substitute and to accelerate the identification of novel and consistent predictive analytes cost-efficiently. However, the utility of tumor profiling is currently limited in OMPC due to the lack of clinically validated predictive biomarkers. In this scenario, different ongoing trials, such as the RADIOSA trial, might provide additional insights into the biology of the oligometastatic state and on the identification of novel biomarkers for the outlining of true oligometastatic patients, paving the way towards a wider ideal approach of personalized medicine. The aim of the present narrative review is to report the current state of the art on the solidity of liquid biopsy-related analytes such as CTCs, cfDNA, miRNA and epi-miRNA, and to provide a benchmark for their further clinical implementation. Arguably, this kind of molecular profiling could refine current developments in the era of precision oncology and lead to more refined therapeutic strategies in this subset of oligometastatic patients.

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“…Moya et al ( 59 ) identified one of the four plasma miRNAs (a highly expressed miR-152) that has the potential to improve the diagnostic power of the existing PSA biomarker for PCa. In a preliminary study ( 25 ), we found that the increase in the expression of miR-152 as a result of promoter hypomethylation was directly proportional to PSA, GS and TNM staging in both PCa and Met-PCa groups. Our results did not support the finding of the study by Zhu et al ( 53 ), Theodore et al ( 54 ) and Ramalho-Carvalho et al ( 86 ).…”

Section: Discussionmentioning

confidence: 89%

“…It was demonstrated that there is an inverse proportion between the expression level of miR-34 and DNMTs. In a preliminary study ( 25 ), it was found that the percentages of promoter methylation of miR-34b and miR-34c decreased in the PCa and Met-PCa groups, and this hypomethylation resulted in an increased expression level of miR-34b/c. Furthermore, high miR-34b/c levels were associated directly with PSA, GS and TNM staging.…”

Section: Discussionmentioning

confidence: 99%

“…In a preliminary study where miR-34b/c, miR-148a and miR-152 were identified as prognostic onco-miR biomarker candidates in PCa, it was found that these epi-miRNAs were correlated with the clinicopathological (PSA, GS and TNM-Staging) characteristics of the patients ( 25 ). It was also reported that miR-200a/b acted as an onco-miR in the early stage of PCa and a tumor suppressing miR in the advanced metastatic stage.…”

Section: Introductionmentioning

confidence: 99%

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miR‑148a, miR‑152 and miR‑200b promote prostate cancer metastasis by targeting DNMT1 and PTEN expression

et al. 2021

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MicroRNAs (miRs) modulate the expression of target genes in the signal pathway on transcriptome level. The present study investigated the ‘epigenetic-based miRNA (epi-miRNA)-mRNA’ regulatory network of miR-34b, miR-34c, miR-148a, miR-152, miR-200a and miR-200b epi-miRNAs and their target genes, DNA methyltransferase (DNMT1, 3a and 3b), phosphate and tensin homolog (PTEN) and NK3 Homeobox 1 (NKX3.1), in prostate cancer (PCa) using reverse transcription-quantitative PCR. The expression level of NKX3.1 were not significantly different between the PCa, Met-PCa and control groups. However, in the PCa and Met-PCa groups, the expression level of DNMT1 was upregulated, while DNMT3a, DNMT3b and PTEN were downregulated. Overexpression of DNMT1 (~5 and ~6-fold increase in the PCa and Met-PCa groups respectively) was accompanied by a decreased expression in PTEN, indicating a potential negative association. Both groups indicated that a high level of DNMT1 is associated with the aggressiveness of cancer, and there is a a directly proportional relationship between this gene and PSA, GS and TNM staging. A significant ~2 to ~5-fold decrease in the expression levels of DNMT3a and DNMT3b was found in both groups. In the PCa group, significant associations were identified between miR-34b and DNMT1/DNMT3b; between miR-34c/miR-148a and all target genes; between miR-152 and DNMT1/DNMT3b and PTEN; and between miR-200a/b and DNMT1. In the Met-PCa group, miR-148a, miR-152 and miR-200b exhibited a significant association with all target genes. A significant negative association was identified between PTEN and DNMT1 in the Met-PCa group. It was also revealed that that miR-148a, miR-152 and miR-200b increased the expression of DNMT1 and suppressed PTEN. Furthermore, the ‘epi-miRNA-mRNA’ bidirectional feedback loop was emphasised and the methylation pattern in PCa anti-cancer therapeutics was highlighted.

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Comparative analysis of epi-miRNA expression levels in local/locally advanced and metastatic prostate cancer patients

Cited by 10 publications

References 40 publications

MiR-182-5p and miR-375-3p Have Higher Performance Than PSA in Discriminating Prostate Cancer from Benign Prostate Hyperplasia

MiR-182-5p and miR-375-3p Have Higher Performance Than PSA in Discriminating Prostate Cancer from Benign Prostate Hyperplasia

Exploring miRNA Signature and Other Potential Biomarkers for Oligometastatic Prostate Cancer Characterization: The Biological Challenge behind Clinical Practice. A Narrative Review

miR‑148a, miR‑152 and miR‑200b promote prostate cancer metastasis by targeting DNMT1 and PTEN expression

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