Serum MicroRNAs Are Promising Novel Biomarkers

Gilad, Shlomit; Meiri, Eti; Yogev, Yariv; Schwessinger, Benjamin; Lebanony, Danit; Yerushalmi, Noga; Benjamin, H.; Kushnir, Michal; Cholakh, Hila; Melamed, Nir; Bentwich, Zvi; Hod, Moshe; Goren, Yaron; Chajut, Ayelet

doi:10.1371/journal.pone.0003148

Cited by 1,243 publications

(959 citation statements)

References 23 publications

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“…[27][28][29] Our micro-RNA-based qRT-PCR test has been developed and validated using retrospective FFPE samples with established primary origins. Our technology is highly sensitive and is applicable also to fresh frozen and small samples such as are obtained with fine needle aspirates.…”

Section: Discussionmentioning

confidence: 99%

“…qRT-PCR was performed as described, 23,27 using probes for the 104 candidate microRNAs, of which five were tested with two different forward primers, and for U6 snoRNA.…”

Section: Qrt-pcrmentioning

confidence: 99%

“…27 A recently described diagnostic test for sub-classification of non-small cell lung carcinoma uses this same technology. 23 We previously showed the performance and reproducibility of this platform, as well as the correlation of data obtained to microRNA arrays.…”

Section: Tissue Classification By Microrna Qrt-pcrmentioning

confidence: 99%

“…[23][24][25][26] MicroRNAs are also stable in tissue, stored frozen or as formalinfixed, paraffin-embedded (FFPE) samples, and in serum. [27][28][29] In an earlier work, we showed that a biologically motivated classifier based on expression of a relatively small number of tissue-specific microRNAs allows tumor tissues of origin to be accurately identified. 26 A small number of markers can be measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), which is a well-established platform for diagnostic assays.…”

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confidence: 99%

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Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

et al. 2010

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Identification of the tissue of origin of a tumor is vital to its management. Previous studies showed tissuespecific expression patterns of microRNA and suggested that microRNA profiling would be useful in addressing this diagnostic challenge. MicroRNAs are well preserved in formalin-fixed, paraffin-embedded (FFPE) samples, further supporting this approach. To develop a standardized assay for identification of the tissue origin of FFPE tumor samples, we used microarray data from 504 tumor samples to select a shortlist of 104 microRNA biomarker candidates. These 104 microRNAs were profiled by proprietary quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) on 356 FFPE tumor samples. A total of 48 microRNAs were chosen from this list of candidates and used to train a classifier. We developed a clinical test for the identification of the tumor tissue of origin based on a standardized protocol and defined the classification criteria. The test measures expression levels of 48 microRNAs by qRT-PCR, and predicts the tissue of origin among 25 possible classes, corresponding to 17 distinct tissues and organs. The biologically motivated classifier combines the predictions generated by a binary decision tree and K-nearest neighbors (KNN). The classifier was validated on an independent, blinded set of 204 FFPE tumor samples, including nearly 100 metastatic tumor samples. The test predictions correctly identified the reference diagnosis in 85% of the cases. In 66% of the cases the two algorithm predictions (tree and KNN) agreed on a single-tissue origin, which was identical to the reference diagnosis in 90% of cases. Thus, a qRT-PCR test based on the expression profile of 48 tissue-specific microRNAs allows accurate identification of the tumor tissue of origin.

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Section: Discussionmentioning

confidence: 99%

“…qRT-PCR was performed as described, 23,27 using probes for the 104 candidate microRNAs, of which five were tested with two different forward primers, and for U6 snoRNA.…”

Section: Qrt-pcrmentioning

confidence: 99%

Section: Tissue Classification By Microrna Qrt-pcrmentioning

confidence: 99%

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confidence: 99%

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Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

et al. 2010

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“…[5][6][7] In addition, reliable methods for extracting miRNAs from bodily fluids, such as serum, have been well developed and well validated. 8,9 Therefore, serum miRNAs could represent novel biomarkers for PCa. 10,11 A study of plasma samples from PCa patients reported that plasma miR-141 levels can be used to screen for metastatic PCa with high sensitivity.…”

Section: Introductionmentioning

confidence: 99%

An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

Zhang¹,

Xiao²,

Cao³

et al. 2013

Asian J Androl

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The skeleton is the most common metastatic organ in patients with prostate cancer (PCa). Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable. We designed this study to assess the expression patterns of serum miR-141 in patients with bone-metastatic PCa. Serum samples were collected to measure the miR-141 level in 56 patients, including six with benign prostatic hyperplasia (BPH), 20 with localized PCa and 30 with bone-metastatic PCa (10 with hormone-naive PCa, 10 with hormone-sensitive PCa and 10 with hormone-refractory PCa). A bone scan was performed for each patient with PCa to assess the number of bone lesions. The quantification of serum miR-141 levels was assayed by specific TaqMan qRT-PCR. The results showed that serum miR-141 levels were elevated in patients with bone metastasis (P,0.001). There was no statistically significant difference in the serum miR-141 levels between patients with BPH and patients with localized PCa. Using Kendall's bivariate correlation test, both the Gleason score and the number of bone-metastatic lesions were found to correlate with serum miR-141 levels (P50.012 and P,0.001, respectively). The serum miR-141 level was found to be positively correlated with alkaline phosphatase (ALP) level in patients with skeletal metastasis, using Pearson's bivariate correlation test. No relationship was found between the serum miR-141 level and the serum prostate-specific antigen (PSA) level. We concluded that serum miR-141 levels are elevated in patients with bone-metastatic PCa and that patients with higher levels of serum miR-141 developed more bone lesions. Furthermore, serum miR-141 levels are correlated with serum ALP levels but not serum PSA levels.

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Association of Salivary MicroRNA Changes With Prolonged Concussion Symptoms

et al. 2018

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IMPORTANCE Approximately one-third of children who experience a concussion develop prolonged concussion symptoms. To our knowledge, there are currently no objective or easily administered tests for predicting prolonged concussion symptoms. Several studies have identified alterations in epigenetic molecules known as microRNAs (miRNAs) following traumatic brain injury. No studies have examined whether miRNA expression can detect prolonged concussion symptoms. OBJECTIVE To evaluate the efficacy of salivary miRNAs for identifying children with concussion who are at risk for prolonged symptoms. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study at the Penn State Medical Center observed 52 patients aged 7 to 21 years presenting for evaluation of concussion within 14 days of initial head injury, with follow-up at 4 and 8 weeks. EXPOSURES All patients had a clinical diagnosis of concussion. MAIN OUTCOMES AND MEASURES Salivary miRNA expression was measured at the time of initial clinical presentation in all patients. Patients with a Sport Concussion Assessment Tool (SCAT3) symptom score of 5 or greater on self-report or parent report 4 weeks after injury were designated as having prolonged symptoms. RESULTS Of the 52 included participants, 22 (42%) were female, and the mean (SD) age was 14 (3) years. Participants were split into the prolonged symptom group (n = 30) and acute symptom group (n = 22). Concentrations of 15 salivary miRNAs spatially differentiated prolonged and acute symptom groups on partial least squares discriminant analysis and demonstrated functional relationships with neuronal regulatory pathways. Levels of 5 miRNAs (miR-320c-1, miR-133a-5p, miR-769-5p, let-7a-3p, and miR-1307-3p) accurately identified patients with prolonged symptoms on logistic regression (area under the curve, 0.856; 95% CI, 0.822-0.890). This accuracy exceeded accuracy of symptom burden on child (area under the curve, 0.649; 95% CI, 0.388-0.887) or parent (area under the curve, 0.562; 95% CI, 0.219-0.734) SCAT3 score. Levels of 3 miRNAs were associated with specific symptoms 4 weeks after injury; miR-320c-1 was associated with memory difficulty (R, 0.55; false detection rate, 0.02), miR-629 was associated with headaches (R, 0.47; false detection rate, 0.04), and let-7b-5p was associated with fatigue (R, 0.45; false detection rate, 0.04). CONCLUSIONS AND RELEVANCE Salivary miRNA levels may identify the duration and character of concussion symptoms. This could reduce parental anxiety and improve care by providing a tool for concussion management. Further validation of this approach is needed.

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Serum MicroRNAs Are Promising Novel Biomarkers

Cited by 1,243 publications

References 23 publications

Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

Association of Salivary MicroRNA Changes With Prolonged Concussion Symptoms

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