Two Panels of Plasma MicroRNAs as Non-Invasive Biomarkers for Prediction of Recurrence in Resectable NSCLC

Sanfiorenzo, C.; Ilié, Marius; Belaïd, Amine; Barlési, Fabrice; Mouroux, Jérôme; Marquette, Charles-Hugo; Brest, Patrick; Hofman, Paul

doi:10.1371/journal.pone.0054596

Cited by 154 publications

(155 citation statements)

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“…This may be due to the breakdown of the miRNA in the plasma samples. However, the majority of the previous studies in NSCLC did not examine the exosomal miRNAs separated from the plasma or serum, which would likely include the intact miRNA (7)(8)(9)(10)(11)(12)(13)(26)(27)(28)(29). In the present study, microarray-based expression profiling of miRNAs derived from exosomes in the plasma of 6 NSCLC patients with or without recurrence was employed.…”

Section: Discussionmentioning

confidence: 99%

“…Sanfiorenzo et al showed the importance of the two panels of plasma miRNAs for the prediction of recurrence in NSCLC patients (28). The study reported that one miRNA panel (high miR-155-5p, high miR-223-3p and low miR-126a-3p) was significantly associated with a higher progression risk in adenocarcinoma patients, and that another miRNA panel (high miR-20a-5p, low miR-152-3p and low miR-199a-5p) was significant in the prediction of likely survival rates of squamous cell carcinoma patients.…”

Section: Discussionmentioning

confidence: 99%

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Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer

et al. 2017

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Abstract. Predictive biomarkers for the recurrence of non-small cell lung cancer (NSCLC) in patients who have received curative resection are important for cancer treatment. The functional microRNAs (miRNAs/miRs) in the exosomes of plasma and serum samples are of interest as stable and non-invasive biomarkers for recurrence in cancer patients. The aim of the present study was to clarify the usefulness of plasma exosomal miRNAs as biomarkers for the prediction of recurrence in NSCLC following curative resection. First, microarray-based expression profiling of miRNAs derived from exosomes in the plasma of 6 patients was employed to identify a biomarker that distinguishes between patients with and without NSCLC recurrence. In the miRNA microarray analyses, the exosomal miR-21 and miR-4257 levels of the NSCLC patients showed marked upregulation in those individuals with recurrence compared with those without recurrence and healthy individuals. These two miRNAs were thus selected as recurrence-specific biomarkers and their potential was evaluated in a separate cohort of 195 NSCLC patients. In comparison to the levels in 30 healthy individuals, exosomal miR-21 and miR-4257 levels showed a significant increase in the NSCLC patients (P<0.01). When evaluating the clinicopathological significance of these miRNAs, exosomal miR-21 showed a significant association with tumor size and tumor-node-metastasis (TNM) stage (P<0.05). Exosomal miR-4257 showed a significant association with histological type, lymphatic invasion and TNM stage (P<0.05). The disease-free survival (DFS) rates of high exosomal miR-21 patients were significantly worse than those of low exosomal miR-21 patients (P<0.05), and the DFS rates of patients with high exosomal miR-4257 levels were significantly worse than those with low exosomal miR-4257 levels (P<0.01). In the Cox multivariate analysis, plasma exosomal miR-21 and miR-4257 expression showed a significance association with DFS (P<0.05). These results suggest that plasma exosomal miR-21 and mir-4257 expression has potential as a predictive biomarker for recurrence in NSCLC patients who have received curative resection. IntroductionLung cancer, mainly non-small cell lung cancer (NSCLC), is the leading cause of cancer-associated mortality globally. More than 133,000 new diagnoses and over 77,000 associated mortalities are expected to occur in 2015 in Japan (1). In spite of progress in NSCLC therapy, the prognosis for patients with NSCLC remains poor (2). Therefore, clarification of the biomarkers most likely to predict the recurrence of NSCLC after curative surgery is required to improve the outcome of NSCLC patients.MicroRNAs (miRNAs/miRs) are one of the most compelling molecular markers in the diagnosis and prognosis of tumors (3,4). miRNAs are short (20-24 nt) non-coding RNAs that take part in the post-transcriptional regulation of gene expression in multicellular organisms by impacting mRNA stability and translation. miRNAs target protein-coding mRNAs at the post-transcriptional level by directly c...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer

et al. 2017

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“…In contrast to mRNAs and proteins, miRNAs are not involved in complex post-transcriptional and post-transcriptional modification. Considering the limitations of condition and time for tissue sampling (Freidin et al 2012), circulating miRNAs are optimal prog- nostic biomarkers for cancer (Sanfiorenzo et al 2013;Chen et al 2013b;Lin et al 2013;Greenberg et al 2013;Kim et al 2013). However, further studies should be conducted before miRNA can be extensively used in clinical applications.…”

Section: Discussionmentioning

confidence: 99%

“…The unique expression profile of circulating miRNA may function as the fingerprint of different diseases because miRNAs are highly stable in serum and plasma (Chen et al 2008). Circulating miRNA has been considered as a potential non-invasive biomarker in tumor diagnosis and prognosis (Sanfiorenzo et al 2013;Chen et al 2013b;Lin et al 2013;Greenberg et al 2013;Kim et al 2013;Rani et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of miR-19b and miR-146a as Prognostic Biomarkers for Non-Small Cell Lung Cancer

Cao

et al. 2014

Tohoku J. Exp. Med.

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MicroRNA (miRNA) is a type of small non-coding RNA molecule that has important roles in cancer initiation, promotion and progression by negatively regulating gene expression. In this study, we explored the role of miRNAs in the prognosis of patients with non-small cell lung cancer (NSCLC). The miRNA expression profiles were determined in 5 pairs of NSCLC and paracancerous tissues (3 adenocarcinomas and 2 squamous cell carcinomas). Aberrantly expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR) in 61 pairs of NSCLC and paracancerous tissues. Differentially expressed miRNAs were further analyzed in sera from 94 healthy subjects and 94 advanced NSCLC patients receiving platinumbased chemotherapy. Three miRNAs (miR-19b, miR-146a, and miR-223) were significantly dysregulated in NSCLC tissues (P < 0.05). High miR-19b and low miR-146a expression in NSCLC tissues were associated with higher TNM stage, lymph node metastasis and poorer survival (P < 0.05). The serum levels of miR-19b in NSCLC patients were significantly higher (P < 0.001), whereas serum levels of miR-146a were significantly lower (P < 0.001), compared with those in controls. Serum levels of miR-19b and miR-146a were associated with overall survival of NSCLC patients (P < 0.05). Patients with low serum level of miR-19b and high serum level of miR-146a achieved a higher overall response rate and longer survival time (P < 0.05). These data suggest that miR-19b and miR-146a are potential biomarkers for the prediction of survival and response to chemotherapy in NSCLC.

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“…Microarray-based studies have identified a large number of differentially expressed miRNAs in primary fibroblasts and lung tissue from patients with COPD [40][41][42]. Many of the miRNAs implicated in COPD have also been associated with various cancers, whereas miRNA that discriminated COPD from lung cancer have also been identified, including miRNAs 26a, 641, 383, 940, 662, 92a, 369-5p, and 636 [43] and miRNAs 20a, 24, 25, 152, 145, 199a [43]. Reduced expression of miR-199a-5p was reported in regulatory T cells from patients with COPD.…”

Section: Microrna-silencing Rnamentioning

confidence: 99%

Genetics Association and Epigenetic Changes in COPD

Malhotra¹,

Vaarala²

2018

COPD - An Update in Pathogenesis and Clinical Management

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Genome-wide association studies (GWASs) have successfully identified susceptibility loci associated with COPD. The genes mapped on these loci, eg The FAM13A gene (family with sequence similarity 13, member A), provide a new approach to understand the COPD pathology. Furthermore, heavy smoking is reported to correlate with altered methylation and epigenetic changes of multiple genes in small airway cells. These changes have been shown to be associated with the severity of COPD. It is likely that smoking-induced changes in epigenetic control of gene expression result in genetically vulnerable individual's results in reduced tissue repair, tissue damage and persistent inflammation associated with COPD pathophysiology.

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Two Panels of Plasma MicroRNAs as Non-Invasive Biomarkers for Prediction of Recurrence in Resectable NSCLC

Cited by 154 publications

References 48 publications

Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer

Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer

Serum Levels of miR-19b and miR-146a as Prognostic Biomarkers for Non-Small Cell Lung Cancer

Genetics Association and Epigenetic Changes in COPD

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