A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer

Halvorsen, Ann Rita; Bjaanæs, Maria Moksnes; LeBlanc, Marissa; Holm, Are Martin; Bolstad, Nils; Rubio, Luis; Peñalver, J.C.; Cervera, José; Mojarrieta, Julia Cruz; Löpez‐Guerrero, José Antonio; Brustugun, Odd Terje; Helland, Åslaug

doi:10.18632/oncotarget.9363

Cited by 83 publications

(79 citation statements)

References 46 publications

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“…To test if our microRNA-signature was predictive of therapy response or barely prognostic, we inspected the same microRNAs analyzed in a previous study on NSCLC [27]. Profiling of microRNAs was performed in serum of 38 surgical resected NSCLC patients, 16 COPD patients and 16 healthy volunteers.…”

Section: Resultsmentioning

confidence: 99%

Circulating microRNAs associated with prolonged overall survival in lung cancer patients treated with nivolumab

et al. 2018

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Background: The introduction of immune check-point inhibition in non-small cell lung cancer (NSCLC) therapy represents improved prospects for the patients. The response rates to check-point inhibitors are approximately 20% in unselected NSCLC patients. Increasing levels of tumor PD-L1 expression are associated with higher response rates. However, patients with low PD-L1 levels may also have durable responses, and improved strategies for patient stratification are needed. Material and methods: In this study, we investigated circulating microRNAs aiming to identify circulating predictive biomarkers associated with increased overall survival after immune check-point treatment. Using next generation sequencing, we performed microRNA profiling in serum from NSCLC patients (n ¼ 20) treated with nivolumab. Serum samples from 31 patients were used for validation using qPCR assays. Serum samples were collected prior to immune therapy initiation. Results: Based on multivariate regression analysis, we identified a signature of seven microRNAs (miR-215-5p, miR-411-3p, miR-493-5p, miR-494-3p, miR-495-3p, miR-548j-5p and miR-93-3p) significantly associated with overall survival (OS) > 6 months in discovery cohort (p ¼ .0003). We further validated this in another similar set of samples (n ¼ 31) and the model was significantly associated with overall survival (OS) > 6 months (p ¼ .001) with sensitivity and specificity of 71% and 90%, respectively. Conclusions: In this study of circulating microRNAs, we have identified a 7-miR signature associated with survival in nivolumab-treated NSCLC patients. This signature may lead to better treatment options for patients with NSCLC, but a validation in an independent cohort is needed to confirm the predicted potential.

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Section: Resultsmentioning

confidence: 99%

Circulating microRNAs associated with prolonged overall survival in lung cancer patients treated with nivolumab

et al. 2018

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“…The remaining 88 articles were selected for full‐text reading, of which 71 articles were removed: 14 using disease controls, 16 without reporting sensitivity, specificity or AUC values, and 41 reporting in non‐Western countries. In the end, 17 studies evaluating the diagnostic performance of circulating miRNAs in serum or plasma for LC detection published between 2011 and 2017 (Tables and ) were eligible for this systematic review …”

Section: Resultsmentioning

confidence: 99%

Circulating microRNA biomarkers for lung cancer detection in Western populations

Guan

Ćuk

et al. 2018

Cancer Medicine

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Lung cancer (LC) is a leading cause of cancer‐related death in the Western world. Patients with LC usually have poor prognosis due to the difficulties in detecting tumors at early stages. Multiple studies have shown that circulating miRNAs might be promising biomarkers for early detection of LC. We aimed to provide an overview of published studies on circulating miRNA markers for early detection of LC and to summarize their diagnostic performance in Western populations. A systematic literature search was performed in PubMed and ISI Web of Knowledge to find relevant studies published up to 11 August 2017. Information on study design, population characteristics, miRNA markers, and diagnostic accuracy (including sensitivity, specificity, and AUC) were independently extracted by two reviewers. Overall, 17 studies evaluating 35 circulating miRNA markers and 19 miRNA panels in serum or plasma were included. The median sensitivity (range) and specificity (range) were, respectively, 78.4% (51.7%‐100%) and 78.7% (42.9%‐93.5%) for individual miRNAs, and 83.0% (64.0%‐100%) and 84.9% (71.0%‐100%) for miRNA panels. Most studies incorporated individual miRNA markers as panels (with 2‐34 markers), with multiple miRNA‐based panels generally outperforming individual markers. Two promising miRNA panels were discovered and verified in prospective cohorts. Of note, both studies exclusively applied miRNA ratios when building up panels. In conclusion, circulating miRNAs may bear potential for noninvasive LC screening, but large studies conducted in screening or longitudinal settings are needed to validate the promising results and optimize the marker panels.

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“…Due to its differential expression in serum among cancer patients and healthy individuals, this miRNA has been considered a new biomarker for early detection of cancer [39, 40]. …”

Section: Discussionmentioning

confidence: 99%

Differentially expressed miRNAs in triple negative breast cancer between African-American and non-Hispanic white women

et al. 2016

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Triple Negative Breast Cancer (TNBC), a clinically aggressive subtype of breast cancer, disproportionately affects African American (AA) women when compared to non-Hispanic Whites (NHW). MiRNAs(miRNAs) play a critical role in these tumors, through the regulation of cancer driver genes. In this study, our goal was to characterize and compare the patterns of miRNA expression in TNBC of AA (n = 27) and NHW women (n = 30). A total of 256 miRNAs were differentially expressed between these groups, and distinct from the ones observed in their respective non-TNBC subtypes. Fifty-five of these miRNAs were mapped in cytobands carrying copy number alterations (CNAs); 26 of them presented expression levels concordant with the observed CNAs. Receiving operating characteristic (ROC) analysis showed a good power (AUC ≥ 0.80; 95% CI) for over 65% of the individual miRNAs and a high combined power with superior sensitivity and specificity (AUC = 0.88 (0.78−0.99); 95% CI) of the 26 miRNA panel in discriminating TNBC between these populations. Subsequent miRNA target analysis revealed their involvement in the interconnected PI3K/AKT, MAPK and insulin signaling pathways. Additionally, three miRNAs of this panel were associated with early age at diagnosis. Altogether, these findings indicated that there are different patterns of miRNA expression between TNBC of AA and NHW women and that their mapping in genomic regions with high levels of CNAs is not merely physical, but biologically relevant to the TNBC phenotype. Once validated in distinct cohorts of AA women, this panel can potentially represent their intrinsic TNBC genome signature.

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A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer

Cited by 83 publications

References 46 publications

Circulating microRNAs associated with prolonged overall survival in lung cancer patients treated with nivolumab

Circulating microRNAs associated with prolonged overall survival in lung cancer patients treated with nivolumab

Circulating microRNA biomarkers for lung cancer detection in Western populations

Differentially expressed miRNAs in triple negative breast cancer between African-American and non-Hispanic white women

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