Exosomal miR-1290 and miR-375 as Prognostic Markers in Castration-resistant Prostate Cancer
By Xiaoyi Huang, Tiezheng Yuan, Meihua Liang, Meijun Du, Shu Xia, Rachel L. Dittmar, Dian Wang, W. See, B. Costello, F. Quevedo and 11 more. European Urology, 2014
633 citations recorded by the source corpus.
Background Extracellular microRNAs (miRNAs) embedded in circulating exosomes may serves as prognostic biomarkers in cancer. Objective To identify and evaluate plasma exosomal miRNAs for prognosis in castration-resistant prostate cancer (CRPC). Design, setting, and participants RNA sequencing was performed to identify candidate exosomal miRNAs associated with overall survival in a screening cohort of 23 CRPC patients. Candidate miRNAs were further evaluated for prognosis using quantitative real-time polymerase chain reaction in a follow-up cohort of 100 CRPC patients. Outcome measurements and statistical analysis Cox regression and Kaplan-Meier survival analyses were used to evaluate survival association using candidate miRNAs along with clinical prognostic factors. Results and limitations RNA sequencing in screening cohort generated approximately 6.80 million mappable reads per patient. Of those with normalized read counts ≥5, 43% were mapped to miRNAs for a total of 375 known and 57 novel miRNAs. Cox regression analysis identified an association of miR-1290, -1246, and -375 with overall survival (false discover rate <0.05). Of those, higher levels of miR-1290 and -375 were significantly associated with poor overall survival (p < 0.004) in the follow-up cohort. Incorporation of miR-1290/-375 into putative clinical prognostic factors-based models in CRPC stage significantly improved predictive performance with a time-dependent area under the curve increase from 0.66 to 0.73 (p = 6.57 × 10−6). Conclusions Plasma exosomal miR-1290 and miR-375 are promising prognostic biomarkers for CRPC patients. Prospective validation is needed for further development of these candidate miRNAs. Patient summary In this study, we evaluated whether small RNAs circulating in blood could be used to predict clinical outcomes in late-stage prostate cancer patients. We identified two blood-based small RNAs whose levels showed significant association with survival. Our results warrant further investigation because the noninvasive blood-based test has great potential in the management of late-stage prostate cancer.
Subfields: Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/13a91b40a838190bdade27164643e73df900f446
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In Molecular Biology
Citations in the corpus
- Precision Cancer Medicine: Challenges and Opportunities (2019, background): “HER2 inhibition by the TKI lapatinib induces upregulation of HER3 in vitro, which as mentioned previously can lead to resistance [115].”
- Effect of exosomal miRNA on cancer biology and clinical applications (2018, background): “Additionally, miR-1290 and miR-375 upregulation might indicate poor overall survival in castration-resistant prostate cancer [75], and exosomal miR-19a cluster expression level in serumarecorrelated with recurrence in colorectal cancer [76].”
- Extracellular vesicles in cancer: cell-to-cell mediators of metastasis (2016, background): “Another study associated higher levels of miR-1290 and miR-375 within serum exosomes with decreased survival in patients with castration-resistant tumors (Huang et al., 2015).”