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Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients.

ABSTRACT: We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p<.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions.

SUBMITTER: Singh PK

PROVIDER: S-EPMC3996656 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients.

Singh Prashant K PK Preus Leah L Hu Qiang Q Yan Li L Long Mark D MD Morrison Carl D CD Nesline Mary M Johnson Candace S CS Koochekpour Shahriar S Kohli Manish M Liu Song S Trump Donald L DL Sucheston-Campbell Lara E LE Campbell Moray J MJ

Oncotarget 20140201 3

We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of C ...[more]

PMID: 24583788

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Project description:BackgroundThe identification of additional prognostic markers to improve risk stratification and to avoid overtreatment is one of the most urgent clinical needs in prostate cancer (PCa). MicroRNAs, being important regulators of gene expression, are promising biomarkers in various cancer entities, though the impact as prognostic predictors in PCa is poorly understood. The aim of this study was to identify specific miRNAs as potential prognostic markers in high-risk PCa and to validate their clinical impact.Methodology and principal findingsWe performed miRNA-microarray analysis in a high-risk PCa study group selected by their clinical outcome (clinical progression free survival (CPFS) vs. clinical failure (CF)). We identified seven candidate miRNAs (let-7a/b/c, miR-515-3p/5p, -181b, -146b, and -361) that showed differential expression between both groups. Further qRT-PCR analysis revealed down-regulation of members of the let-7 family in the majority of a large, well-characterized high-risk PCa cohort (n = 98). Expression of let-7a/b/and -c was correlated to clinical outcome parameters of this group. While let-7a showed no association or correlation with clinical relevant data, let-7b and let-7c were associated with CF in PCa patients and functioned partially as independent prognostic marker. Validation of the data using an independent high-risk study cohort revealed that let-7b, but not let-7c, has impact as an independent prognostic marker for BCR and CF. Furthermore, we identified HMGA1, a non-histone protein, as a new target of let-7b and found correlation of let-7b down-regulation with HMGA1 over-expression in primary PCa samples.ConclusionOur findings define a distinct miRNA expression profile in PCa cases with early CF and identified let-7b as prognostic biomarker in high-risk PCa. This study highlights the importance of let-7b as tumor suppressor miRNA in high-risk PCa and presents a basis to improve individual therapy for high-risk PCa patients.

Project description:PURPOSE:Novel biomarkers for the diagnosis of prostate cancer (PCa) are urgently required. Increasing evidence suggests that exosomal microRNAs (miRNAs or miRs) in serum may be potential noninvasive biomarkers for certain diseases. The objective of the present study was to investigate and assess whether exosomal miR-141 is an effective biomarker for human PCa. METHODS:In the present study, exosomes were isolated from the serum of patients with PCa, patients with benign prostate hyperplasia (BPH), and healthy volunteers. The total RNA was extracted from the exosomes and the level of miR-141 was analyzed by quantitative reverse transcription-polymerase chain reaction. The expression levels of miR-141 were compared between the whole serum and the serum exosomes of the three groups. Subsequently, the relevance of the exosomal expression of miR-141 to the clinicopathological factors in PCa was investigated. RESULTS:The expression of miR-141 was higher in exosomes compared with whole serum (control group, P=0.0003; BPH group, P=0.0016; PCa group, P<0.0001). The level of serum exosomal miR-141 was significantly higher in the patients with PCa compared with the patients with BPH and the healthy controls (3.85-fold, P=0.0007 and 4.06-fold, P=0.0005, respectively). In addition, the expression levels were significantly higher in metastatic PCa compared with localized PCa (P<0.0001). Receiver-operating characteristic curve revealed that the serum exosomal miR-141 yielded an area under the curve of 0.8694, with 80% sensitivity and 87.1% specificity in discriminating patients with metastatic PCa from the patients with localized PCa. CONCLUSION:Serum exosomes may serve as a more suitable material compared with the whole serum for measuring circulating miR-141 levels in patients with PCa. Exosomal miR-141 is upregulated in the serum from patients with PCa compared with patients with BPH or the healthy volunteers, and it may be a useful potential biomarker for the diagnosis of metastatic PCa.

Project description:Background: Perturbation of energy metabolism exacerbates cardiac dysfunction, serving as a potential therapeutic target in congestive heart failure. Although circulating free fatty acids (FFAs) are linked to insulin resistance and risk of coronary heart disease, it still remains unclear whether circulating FFAs are associated with the prognosis of patients with acute heart failure (AHF). Methods: This single-center, observational cohort study enrolled 183 AHF patients (de novo heart failure or decompensated chronic heart failure) in the Second Affiliated Hospital, Zhejiang University School of Medicine. All-cause mortality and heart failure (HF) rehospitalization within 1 year after discharge were investigated. Serum FFAs were modeled as quartiles as well as a continuous variable (per SD of FFAs). The restricted cubic splines and cox proportional hazards models were applied to evaluate the association between the serum FFAs level and all-cause mortality or HF rehospitalization. Results: During a 1-year follow-up, a total of 71 (38.8%) patients had all-cause mortality or HF rehospitalization. The levels of serum FFAs positively contributed to the risk of death or HF rehospitalization, which was not associated with the status of insulin resistance. When modeled with restricted cubic splines, the serum FFAs increased linearly for the incidence of death or HF rehospitalization. In a multivariable analysis adjusting for sex, age, body-mass index, coronary artery disease, diabetes mellitus, hypertension, left ventricular ejection fraction and N-terminal pro-brain natriuretic peptid, each SD (303.07 μmol/L) higher FFAs were associated with 26% higher risk of death or HF rehospitalization (95% confidence interval, 2-55%). Each increasing quartile of FFAs was associated with differentially elevated hazard ratios for death or HF rehospitalization of 1 (reference), 1.71 (95% confidence interval, [0.81, 3.62]), 1.41 (95% confidence interval, [0.64, 3.09]), and 3.18 (95% confidence interval, [1.53, 6.63]), respectively. Conclusion: Serum FFA levels at admission among patients with AHF were associated with an increased risk of adverse outcomes. Additional studies are needed to determine the causal-effect relationship between FFAs and acute cardiac dysfunction and whether FFAs could be a potential target for AHF management.

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Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients.

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Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients.

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