Circulating plasma microRNAs as potential markers to identify EGFR mutation status and to monitor epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with advanced non-small cell lung cancer

Abstract

We aimed to identify a panel of circulating plasma microRNAs that can predict EGFR mutation status and monitor epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with non-small cell lung cancer. Microarrays were performed for the preliminary screening of dysregulated microRNAs in 9 EGFR mutation-positive patients versus healthy controls. MiR-107 was upregulated and miR-195 was downregulated in the exon 19 deletion versus wild-type group. The areas under the receiver operating characteristic curves for miR-107, miR-195, and a panel of these 2 microRNAs were 0.72, 0.75, and 0.74, with sensitivities and specificities of 64.7% and 76.6%, 71.8% and 69.1%, and 71.7% and 78.9%, respectively. MiR-122 was significantly upregulated in the p.L858R versus wild-type group. An area under the receiver operative characteristic curve of 0.75 suggests that miR-122 might be a specific biomarker for patients with the p.L858R mutation. In addition, dynamic changes in these 3 microRNAs were also found to correlate with responses to epidermal growth factor receptor-tyrosine kinase inhibitor treatment, indicating that circulating plasma microRNAs may represent potential biomarkers for monitoring epidermal growth factor receptor-tyrosine kinase inhibitor treatment. This study demonstrates the prospective application of circulating plasma microRNAs as potential non-invasive, convenient biomarkers for patients with EGFR-sensitive mutations.

A five‐miRNA panel in plasma was identified for breast cancer diagnosis

“…[27][28][29] The diagnostic or prognostic value of circulating miR-122 was also reported in other cancers such as colorectal cancer and non-small cell lung cancer, indicating its close connection with tumor biological processes. [30][31][32] Circulating miR-215 was previously found to be decreased in plasma in progressive BC patients in comparison with those who did not, but van Schooneveld et al showed just the opposite result of increasing tendency in serum in metastatic BC patients. 33,34 In BC tissues, downregulation of miR-215-5p was once reported by Leblanc et al under the effect of its modulator Pax-5, 35 and was also observed by Zhou et al which could act as a predictor for pool clinical outcomes for patients.…”

Unique circulating microRNAs in relation to EGFR mutation status in Japanese smoker male with lung adenocarcinoma

“…Since the molecular target therapy against NSCLC patients harboring somatic mutations in EGFR genes has been evolved, clinical sequencing for mutations in EGFR gene is therefore an important step in the treatment-decision pathway [ 26 ]. Expression profiling of miRNAs associated with EGFR mutational status in tumor tissues and bloodstream have been extensively investigated to translate specific miRNAs as prediction biomarker [ 18 , 25 , 27 , 28 ]. However, there are still limited studies regarding to circulating miRNA expression signatures which enable to distinguish mutation status of EGFR gene in lung adenocarcinoma male patients with smoking history.…”

Profiling of 179 miRNA Expression in Blood Plasma of Lung Cancer Patients and Cancer-Free Individuals

“…This layer of protection plays a critical role in defining their stability and accessibility as disease biomarkers. So far, a number of groups have reported specific subsets of circulating miRNAs in blood that were linked to tumour location, clinical properties, and genetic phenotypes, including certain EGFR mutations and ALK fusion positivity 10 , 14 – 16 . Even more importantly, miRNAs have been proposed as indicators of disease progression, metastasis, patient prognosis and survival 17 – 19 .…”