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Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome.

ABSTRACT: Improved prostate cancer prognostic biomarkers are urgently needed. We previously identified the four-miRNA prognostic biomarker panel MiCaP ((miR-23a-3p?×?miR-10b-5p)/(miR-133a-3p?×?miR-374b-5p)) for prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Here, we identified an optimal numerical cut-off for MiCaP dichotomisation using a training cohort of 475 RP patients and tested this in an independent cohort of 281 RP patients (PCA281). Kaplan-Meier, uni- and multivariate Cox regression analyses were conducted for multiple endpoints: BCR, metastatic-(mPC) and castration-resistant prostate cancer (CRPC), prostate cancer-specific (PCSS) and overall survival (OS). Functional effects of the four MiCaP miRNAs were assessed by overexpression and inhibition experiments in prostate cancer cell lines. We found the numerical value 5.709 optimal for MiCaP dichotomisation. This was independently validated in PCA281, where a high MiCaP score significantly [and independent of the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score] predicted BCR, progression to mPC and CRPC, and PCSS, but not OS. Harrell's C-index increased upon addition of MiCaP to CAPRA-S for all endpoints. Inhibition of miR-23a-3p and miR-10b-5p, and overexpression of miR-133a-3p and miR-374b-5p significantly reduced cell survival. Our results may promote future implementation of a MiCaP-based test for improved prostate cancer risk stratification.

SUBMITTER: Strand SH

PROVIDER: S-EPMC7329825 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome.

Strand Siri H SH Schmidt Linnéa L Weiss Simone S Borre Michael M Kristensen Helle H Rasmussen Anne Karin Ildor AKI Daugaard Tina Fuglsang TF Kristensen Gitte G Stroomberg Hein Vincent HV Røder Martin Andreas MA Brasso Klaus K Mouritzen Peter P Sørensen Karina Dalsgaard KD

Scientific reports 20200701 1

Improved prostate cancer prognostic biomarkers are urgently needed. We previously identified the four-miRNA prognostic biomarker panel MiCaP ((miR-23a-3p × miR-10b-5p)/(miR-133a-3p × miR-374b-5p)) for prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Here, we identified an optimal numerical cut-off for MiCaP dichotomisation using a training cohort of 475 RP patients and tested this in an independent cohort of 281 RP patients (PCA281). Kaplan-Meier, uni- and multivariat ...[more]

PMID: 32612164

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Project description:BackgroundAbout 30% of stroke patients suffer from aphasia. As aphasia strongly affects daily life, most patients request a prediction of outcome of their language function. Prognostic models provide predictions of outcome, but external validation is essential before models can be used in clinical practice. We aim to externally validate the prognostic model from the Sequential Prognostic Evaluation of Aphasia after stroKe (SPEAK-model) for predicting the long-term outcome of aphasia caused by stroke.MethodsWe used data from the Rotterdam Aphasia Therapy Study - 3 (RATS-3), a multicenter RCT with inclusion criteria similar to SPEAK, an observational prospective study. Baseline assessment in SPEAK was four days after stroke and in RATS-3 eight days. Outcome of the SPEAK-model was the Aphasia Severity Rating Scale (ASRS) at 1 year, dichotomized into good (ASRS-score of 4 or 5) and poor outcome (ASRS-score < 4). In RATS-3, ASRS-scores at one year were not available, but we could use six month ASRS-scores as outcome. Model performance was assessed with calibration and discrimination.ResultsWe included 131 stroke patients with first-ever aphasia. At six months, 86 of 124 (68%) had a good outcome, whereas the model predicted 88%. Discrimination of the model was good with an area under the receiver operation characteristic curve of 0.87 (95%CI: 0.81-0.94), but calibration was unsatisfactory. The model overestimated the probability of good outcome (calibration-in-the-large α = - 1.98) and the effect of the predictors was weaker in the validation data than in the derivation data (calibration slope β = 0.88). We therefore recalibrated the model to predict good outcome at six months.ConclusionThe original model, renamed SPEAK-12, has good discriminative properties, but needs further external validation. After additional external validation, the updated SPEAK-model, SPEAK-6, may be used in daily practice to discriminate between patients with good and patients with poor outcome of aphasia at six months after stroke.Trial registrationRATS-3 was registered on January 13th 2012 in the Netherlands Trial Register: NTR3271 . SPEAK was not listed in a trial registry.

Project description:Introduction Four-corner arthrodesis with excision of the scaphoid is an accepted salvage procedure for scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) and has been performed in our unit for over 20 years. We have undertaken a retrospective review of 116 of these procedures performed in 110 patients between 1992 and 2009. Fifty-eight patients attended for a clinical evaluation, and 29 responded by postal questionnaire. Methods The surgical technique undertaken was standard. That is, through a dorsal approach the scaphoid and tip of the radial styloid were excised. The capitate, lunate, triquetrum, and hamate articular surfaces were then prepared down to bleeding bone. Bone grafts from the scaphoid and radial styloid were then inserted and fixation undertaken. For the latter, various methods were used, including Kirschner (K-)wires, staples, bone screws, but predominantly the Spider plate (Integra Life Sciences, USA). Thereafter the wrist was immobilized for a minimum period of 2 weeks prior to rehabilitation. Results Follow-up was done at a mean of 9 years and 4 months (range 3-19 years). All patients reported a significant improvement in pain relief and ∼50% of flexion extension, although only 40% of radioulnar deviation. Grip strength was again ∼50% of the contralateral side. Most patients reported a significant improvement in function with 87% returning to work. In addition, radiologic evaluation identified 28 patients (31%) who demonstrated ongoing signs of nonunion, particularly around the triquetrum. Fourteen of these (15%) underwent a further procedure, generally with success. Finally, none of the patients demonstrated any arthritic changes in the lunate fossa on follow-up X-ray, and all secondary procedures were undertaken within 2 years of the primary. Discussion This research has demonstrated that four-corner fusion fixed with a circular plate can result in a satisfactory outcome with a reduction in pain, a functional range of motion, and a satisfactory functional outcome. The bulk of the complications appear to occur in the first 2 years after surgery. Thereafter, analysis shows long-term satisfaction with little deterioration. Nonunion, particularly around the triquetrum, continues to be a problem, but it may be that this bone should be excised along with the scaphoid, resulting in a three-part fusion only. Alternatively, a simple capitolunate fusion may be satisfactory.

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Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome.

Publications

Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome.

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