Plasma microRNA signature is associated with risk stratification in prostate cancer patients

Al-Qatati, Abeer; Akrong, Christine; Stevic, Ines; Pantel, Klaus; Awe, Julius Adebayo; Saranchuk, Jeff; Drachenberg, Darrel; Mai, Sabine; Schwarzenbach, Heidi

doi:10.1002/ijc.30815

Cited by 44 publications

(34 citation statements)

References 31 publications

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“…Out of the three other miRNAs in bCaP, only miR-16-5p was significantly upregulated in samples from patients with APC, relative to that of samples from patients with BPH or LPC. miR-16-5 has previously displayed elevated expression levels in plasma from LPC patients compared to healthy controls [22,39] as well as elevated expression levels in serum of PC mouse models with bone metastasis [40]. We found no significant changes in expression levels in plasma between samples from BPH or LPC versus APC of either miR-33a-5p or miR-409-3p, indicating that these two miRNAs may simply function as normalization genes in our bCaP model.…”

Section: Discussionmentioning

confidence: 49%

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Fredsøe

Rasmussen²,

Mouritzen³

et al. 2020

Diagnostics

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Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAs in plasma, we confirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375*miR-33a-5p/miR-16-5p*miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

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Section: Discussionmentioning

confidence: 49%

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Fredsøe

Rasmussen²,

Mouritzen³

et al. 2020

Diagnostics

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“…For several microarray biomarkers of PCa, only a few have been tested in large studies and found appropriate. miR‐16, miR‐148a and miR‐195 in plasma were found to be significantly related to a Gleason score ≥ 8, and therefore, miRNAs may differentiate between intermediate‐ and high‐risk Gleason scores (Al‐Qatati et al, ).…”

Section: Discussionmentioning

confidence: 99%

Oxidised low‐density lipoprotein, a possible distinguishing lipid profile biomolecule between prostate cancer and benign prostatic hyperplasia

et al. 2019

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Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) share common conditions such as lower urinary tract symptoms (LUTS) and dyslipidaemia. Whether an extensive lipid profile analysis could discriminate between BPH and PCa was the objective. Thirty‐six (36) BPH and twenty (20) PCa outpatients of a urology clinic plus forty (40) controls without LUTS, but normal PSA, were recruited. Body mass index (BMI), lipid profile (total cholesterol [CHOL], triglycerides [TG], high‐density lipoprotein [HDL], very‐low‐density lipoprotein [VLDL], low‐density lipoprotein [LDL] and Castelli's risk index I [CR I] [TC/HDL]), oxidised LDL, apolipoprotein E, ceramide and PSA were determined. Mean ages for BPH, PCa and control were 69 ± 13, 67 ± 10 and 53 ± 7 years respectively. Most parameters apart from BMI and HDL were significantly different compared to the control group. oxLDL for BPH versus control, PCa versus control and BPH versus PCa was significant (p < 0.001, p = 0.02 and p < 0.001 respectively). Ceramide showed significant group differences. Between BPH and PCa, total cholesterol, LDL and Apo E were significantly different (p = 0.00, p = 0.01 and p = 0.03 respectively). Apo E could potentially be a discriminating biomarker. Receiver operating characteristic curves for TPSA, Apo E and oxLDL demonstrated sensitivity of 69.44 and specificity of 88.24 for oxLDL, hence more discriminatory.

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“…Further analysis using these data [ 6 , 21 , 61 ] found histone modification of miR-148a promoter and AR bindings in the vicinity, suggesting that this miRNA is a direct AR target ( Figure 1 ). Clinical studies have revealed that high miR-148a expression is significantly correlated with prostate cancer progression [ 40 , 62 , 63 ]. Consistent with our finding, subsequent microarray analyses in prostate cancer cell lines and xenograft models have revealed that miR-141 is overexpressed in prostate cancers and CRPCs compared to BPH tissues [ 64 ].…”

Section: Identification Of Androgen-regulated Mirnas In Prostate Cmentioning

confidence: 99%

Significance of microRNAs in Androgen Signaling and Prostate Cancer Progression

Takayama

Misawa

Inoue

2017

Cancers

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The androgen receptor (AR) plays important roles in prostate cancer development and prostate tumor growth. After binding to androgens, AR functions as a nuclear receptor and translocates to the nucleus to bind to specific AR-binding sites (ARBSs). AR regulates epigenetic factor recruitments to activate its downstream signaling. Although androgen deprivation therapy (ADT) is initially useful for prostate cancer patients, most patients eventually show resistance with hormone-refractory prostate cancers (HRPCs) or castration-resistant prostate cancers (CRPCs). Thus, new therapeutic strategies targeting HRPCs/CRPCs should be very important for clinical medicine as well as prostate cancer biology. Past studies have shown that mechanisms such as AR overexpression, hypersensitivity, variants and reprograming are responsible for developing HRPCs/CRPCs. These findings suggest that AR target genes will be major key factors. In this review article, we focus mainly on the androgen-regulated microRNAs (miRNAs) to summarize the contribution of miRNA-mediated pathways for prostate cancer progression.

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Plasma microRNA signature is associated with risk stratification in prostate cancer patients

Cited by 44 publications

References 31 publications

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Oxidised low‐density lipoprotein, a possible distinguishing lipid profile biomolecule between prostate cancer and benign prostatic hyperplasia

Significance of microRNAs in Androgen Signaling and Prostate Cancer Progression

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