scholarly journals Overexpression of miR-20a-5p in Tumor Epithelium Is an Independent Negative Prognostic Indicator in Prostate Cancer—A Multi-Institutional Study

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4096
Author(s):  
Maria J. Stoen ◽  
Sigve Andersen ◽  
Mehrdad Rakaee ◽  
Mona I. Pedersen ◽  
Lise M. Ingebriktsen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariable Analysis ◽  
Cancer Recurrence ◽  
Tumor Stroma ◽  
Tissue Microarrays ◽  
Prognostic Indicator ◽  
Biochemical Failure ◽  
Migration Ability ◽  
Dismal Prognosis

Objective: assessing the prognostic role of miR-20a-5p, in terms of clinical outcome, in a large multi-institutional cohort study. Methods: Tissue microarrays from 535 patients’ prostatectomy specimens were constructed. In situ hybridization was performed to assess the expression level of miR-20a-5p in different tissue subregions: tumor stroma (TS) and tumor epithelium (TE). In vitro analysis was performed on prostate cancer cell lines. Results: A high miR-20a-5p expression was found negatively in association with biochemical failure in TE, TS and TE + TS (p = 0.001, p = 0.003 and p = 0.001, respectively). Multivariable analysis confirmed that high miR-20a-5p expression in TE independently predicts dismal prognosis for biochemical failure (HR = 1.56, 95% CI: 1.10–2.21, p = 0.014). Both DU145 and PC3 cells exhibited increased migration ability after transient overexpression of miR-20a-5p, as well as significant elevation of invasion in DU145 cells. Conclusion: A high miR-20a-5p expression in tumor epithelium is an independent negative predictor for biochemical prostate cancer recurrence.

Intercellular Crosstalk of Mesenchymal Stem Cells with Prostate Cancer Cells via Microvesicles Loaded with Magnetic Nanocubes for Targeted Magnetic Hyperthermia

2019 ◽  
Vol 15 (12) ◽  
pp. 2291-2304
Author(s):  
Liqun Huang ◽  
Mengwei Chen ◽  
Chang Xu ◽  
Qishuai Feng ◽  
Jiaojiao Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Magnetic Hyperthermia ◽  
Migration Ability ◽  
Hyperthermia Therapy

The targeted delivery of nanomedicines into solid tumors remains challenging in cancer treatment. Stem cells with tumortropic migration ability are promising as biocarriers to transport nanomedicines. The transportation of nanomedicines into cancer cells is the key step for tumor targeted delivery via stem cells. In this study, we designed a magnetic nanocube (scMNP) loaded in mesenchymal stem cells for magnetic hyperthermia of prostate cancer, and the delivery and transportation pathways into the cancer cells were fully investigated. The MSCs acted as the carrier of the loaded scMNPs along with the upregulation of CXCR4 for the migration to cancer cells. The therapeutic effect was mainly due to scMNPs via magnetic hyperthermia. Stem cell-derived microvesicles containing scMNPs played an essential role in the crosstalk between stem cells and cancer cells for targeted delivery. Both in vitro and in vivo studies demonstrated that the system showed satisfactory therapeutic efficiency under magnetic hyperthermia therapy. Our investigation presents a comprehensive study of magnetic nanoparticles in combination with MSCs and their extracellular microvesicles and is promising as an effective strategy for magnetic hyperthermia therapy of prostate cancer.

scholarly journals Subcellular localization of p27 and prostate cancer recurrence: automated digital microscopy analysis of tissue microarrays

2011 ◽  
Vol 42 (6) ◽  
pp. 873-881 ◽  
Author(s):  
Viju Ananthanarayanan ◽  
Ryan J. Deaton ◽  
Anup Amatya ◽  
Virgilia Macias ◽  
Ed Luther ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Subcellular Localization ◽  
Cancer Recurrence ◽  
Tissue Microarrays ◽  
Digital Microscopy ◽  
Prostate Cancer Recurrence ◽  
Microscopy Analysis

scholarly journals MicroRNA-219-5p Promotes Tumor Growth and Metastasis of Hepatocellular Carcinoma by Regulating Cadherin 1

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Yang ◽  
Yuan-Yuan Sheng ◽  
Jin-Wang Wei ◽  
Xiao-Mei Gao ◽  
Ying Zhu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Vascular Invasion ◽  
Prognostic Indicator ◽  
Downstream Target ◽  
Dismal Prognosis ◽  
Tumor Growth And Metastasis ◽  
Proliferation And Invasion ◽  
Hcc Cells

MicroRNAs play significant roles in the development of cancer and may serve as promising therapeutic targets. In our previous work, miR-219-5p was identified as one of the important metastasis-related microRNAs in HCC. Here we demonstrated that miR-219-5p expression was elevated in HCC tissues and was associated with vascular invasion and dismal prognosis. In multivariate analysis, miR-219-5p was identified as an independent prognostic indicator for HCC patients. Functional mechanism analyses showed that miR-219-5p promoted HCC cell proliferation and invasion in in vitro, as well as in vivo, tumor growth and metastasis in nude mice models bearing human HCC tumors. In addition, cadherin 1 (CDH1) was revealed to be a downstream target of miR-219-5p in HCC cells. In conclusion, miR-219-5p promotes tumor growth and metastasis of HCC by regulating CDH1 and can serve as a prognostic marker for HCC patients.

scholarly journals High expression of miR-17-5p in tumor epithelium is a predictor for poor prognosis for prostate cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Jenvin Stoen ◽  
S. Andersen ◽  
M. Rakaee ◽  
M. I. Pedersen ◽  
L. M. Ingebriktsen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Cancer Cell ◽  
Tissue Microarrays ◽  
High Expression ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Negative Prognostic Factor ◽  
Independent Negative Prognostic Factor

AbstractMicroRNAs (miRs) are small non-coding RNA molecules, which are involved in the development of various malignancies, including prostate cancer (PCa). miR-17-5p is considered the most prominent member of the miR-17-92 cluster, with an essential regulatory function of fundamental cellular processes. In many malignancies, up-regulation of miR-17-5p is associated with worse outcome. In PCa, miR-17-5p has been reported to increase cell proliferation and the risk of metastasis. In this study, prostatectomy specimens from 535 patients were collected. Tissue microarrays were constructed and in situ hybridization was performed, followed by scoring of miR-17-5p expression on different tumor compartments. High expression of miR-17-5p in tumor epithelium was associated with biochemical failure (BF, p < 0.001) and clinical failure (CF, p = 0.019). In multivariate analyses, high miR-17-5p expression in tumor epithelial cells was an independent negative prognostic factor for BF (HR 1.87, 95% CI 1.32–2.67, p < 0.001). In vitro analyses confirmed association between overexpression of miR-17-5p and proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145). In conclusion, our study suggests that a high cancer cell expression of miR-17-5p was an independent negative prognostic factor in PCa.

Clinical recurrence post-biochemical failure of prostate cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 195-195
Author(s):  
C. A. Reddy ◽  
J. P. Ciezki ◽  
E. A. Klein
Keyword(s):  
Prostate Cancer ◽  
Initial Treatment ◽  
Short Interval ◽  
Multivariable Analysis ◽  
Biochemical Failure ◽  
Early Initiation ◽  
Time Interval ◽  
Clinical Recurrence ◽  
Early Use

195 Background: The purpose of this study is to evaluate the role of salvage therapy (STx) after biochemical failure (bF) for prostate cancer (CaP) and to determine what factors are associated with the development of clinical recurrence (cR). Methods: From 1996-2009, 7,585 patients (pts) with CaP were treated with prostatectomy (RP), brachytherapy (PI), or external beam radiotherapy (RT). For RP patients (pts), bF was defined as a postoperative PSA >0.3 and for PI and RT pts the Phoenix definition was used. bF was documented in 927 pts. cR was defined as any image-based or pathological diagnosis of disease recurrence after bF. Cox proportional hazards regression was used to examine if the use of STx after bF, the time of bF, along with disease characteristics were associated with cR after bF. Results: The median follow-up after bF was 31months (mo; range: 0-131). Thirty percent of pts had a cR after bF, and the 5-year rate of cR free survival was 58%. STx within 1 year after bF (early) was given to 46% of pts, STx more than 1 year after bF (late) was given to 11% of pts, and 43% of pts did not receive STx. On univariate analysis, factors found to be significantly associated (p-value <0.05) with cR were a short interval between initial treatment and bF (bFTime), no use of STx, early initiation of STx, biopsy Gleason Score (bGS), clinical stage, older age at bF, the use of PI or RT, and increased frequency of PSA follow-up after bF (PSAfreq). In multivariable analysis, bFTime, no use of STx, early initiation of STx, bGS, the use of PI or RT, and PSAfreq remained significant. To better evaluate the effect the timing of initiation of STx had on the development of cR, a second analysis was preformed, limited to the 529 pts who did receive STx after bF. In multivariable analysis, early use of STx remained significant for cR (HR=2.09, 95%CI=1.24- 3.51). As a continuous variable, in a second multivariable analysis, delayed use of STx resulted in a reduced risk of developing cR (HR=0.98, 95%CI=0.96-1.00). Conclusions: This study suggests that while the use of STx after bF reduces the risk of subsequently developing cR, early use of STx after bF is not beneficial. Other factors such as the time interval between initial treatment and bF need to be evaluated when determining when to initiate STx after bF. No significant financial relationships to disclose.

scholarly journals MicroRNA Signature Helps Distinguish Early from Late Biochemical Failure in Prostate Cancer

2013 ◽  
Vol 59 (11) ◽  
pp. 1595-1603 ◽  
Author(s):  
Zsuzsanna Lichner ◽  
Annika Fendler ◽  
Carol Saleh ◽  
Aurfan N Nasser ◽  
Dina Boles ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regression Models ◽  
Intensive Therapy ◽  
Specific Antigen ◽  
Risk Groups ◽  
Biochemical Failure ◽  
Small Subset ◽  
Linear Regression Models ◽  
Failure Risk

PURPOSE Prostate-specific antigen testing has led to overtreatment of prostate cancer (PCa). Only a small subset of PCa patients will have an aggressive disease that requires intensive therapy, and there is currently no biomarker to predict disease aggressiveness at the time of surgery. MicroRNAs (miRNAs) are reported to be involved in PCa pathogenesis. METHODS This study involved 105 participants. For the discovery phase, prostatectomy samples were dichotomized to high-risk (n = 27, biochemical failure &lt;36 months after prostatectomy) and low-risk groups (n = 14, ≥36 months without biochemical failure). Expression of 754 mature miRNAs was compared between the 2 groups. Linear regression models were built to accurately predict biochemical failure risk. miRNA mimics were transfected into PCa model cell lines to test effects on proliferation and to deduce responding signaling pathways. RESULTS We identified 25 differentially expressed miRNAs between the biochemical failure risk groups. Based on the expression of 2–3 miRNAs, 3 logistic regression models were developed, each with a high positive predictive value. Candidate miRNAs and the best-performing model were also verified on an independent PCa set. miRNA-152, featured in the models, was further investigated by using cell line models and was shown to affect cell proliferation. Predicted interaction between miR-152 and (mRNA)ERBB3 (erythroblastic leukemia viral oncogene homolog 3) was experimentally validated in vitro. CONCLUSIONS miRNAs can help to predict biochemical failure risk at the time of prostatectomy.

scholarly journals Effect of AXIN2 expression on prostate cancer recurrence and an invasive, tumorigenic phenotype.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 29-29
Author(s):  
Brian Robin Hu ◽  
Adrian S Fairey ◽  
Anisha Madhav ◽  
Dongyun Yang ◽  
Meng Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Recursive Partitioning ◽  
External Validation ◽  
Cancer Recurrence ◽  
Disease Recurrence ◽  
Internal Validation ◽  
Sirna Knockdown

29 Background: Better biomarkers are needed in prostate cancer (PCa) to predict disease recurrence and guide optimal therapy. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor cancer phenotype impact PCa biology and clinical outcomes in localized disease. Methods: Genes associated with self-renewal, drug resistance, and tumorigenicity were analyzed by qRT-PCR on PCa mRNA from radical prostatectomy (RP) specimens (+/- disease recurrence). Wilcoxon rank sum two-sample test, multivariable recursive partitioning, and bootstrap internal validation measured and confirmed associations with recurrence. Further validation was conducted in external cohorts and in-silico, as well as in vitro and in vivo using siRNA knockdown and lentiviral overexpression to determined the effect of gene expression on PCa proliferation, invasion and tumor growth. Results: Four candidate genes were differentially expressed in PCa recurrence, and of these, low AXIN2 expression was internally validated. Validation in external cohorts demonstrated low AXIN2 expression was associated with more aggressive prostate cancer and was independently associated with biochemical recurrence (BCR) and metastasis-free survival (MFS) after RP. In vitro, low AXIN2 expression was associated with a cancer stem-like cell-surface signature, and siRNA knockdown of AXIN2 resulted in significantly greater invasiveness. Conversely, ectopic overexpression of AXIN2 significantly reduced cell proliferation and tumor growth in mice. Conclusions: Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts. AXIN2 expression levels in PCa cells significantly impacted invasiveness, proliferation and tumor growth. AXIN2 represents a putative biomarker and potential therapeutic target in early prostate cancer.

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