Serum exosomal miR‐7977 as a novel biomarker for lung adenocarcinoma

Abstract

Exosomal microRNAs (miRNAs) have great potentials as a novel biomarker to predict lung cancer. We applied a miRNA microarray to identify aberrantly expressed serum exosomal miRNAs as candidate biomarkers for patients with lung adenocarcinoma (LUAD). Compared with the normal control, 31 exosomal miRNAs were found to be upregulated and 29 exosomal miRNAs were downregulated in the serum of LUAD respectively. Then, 10 dysregulated exosomal miRNAs expression levels in serum were further validated via qRT-polymerase chain reaction. Notably, exosomal miR-7977 was highest expressed and miR-98-3p was lowest expressed in the patients with LUAD, and exosomal miR-7977 showed significant correlation with the N stage and TNM stage with patients with LUAD (P < .05). Receiver operating characteristic curve showed that the abundant level of exosomal miR-7977 may predict LUAD with an area of under the curve (AUC) of 0.787. In comparison with exosomal miR-7977, exosomal miR-98-3p had a smaller area (0.719). The combination of exosomal miR-7977 and miR-98-3p improved the AUC to 0.816. Furthermore, in vitro experiments revealed that inhibition of miR-7977 enhanced the proliferation, invasion, and inhibited apoptosis in A549 cells, the opposite results were performed by miR-7977 mimics. In conclusion, exosomal miR-7977 was identified as a novel biomarker for patients with LUAD and may play as a tumor suppressor in lung cancer. K E Y W O R D S exosome, lung cancer, microRNA, miR-7977, qRT-PCR | INTRODUCTIONLung cancer is the leading cause of cancer-related mortality worldwide. This disease is classified into two major subtypes, including non-small cell lung cancer (NSCLC) and small cell lung cancer based on histopathology appearance, accounting for 85% and 15% of all lung cancer, respectively. 1 The main histological type of NSCLC is lung adenocarcinoma (LUAD). 2 While great advances were made in cancer diagnosis and therapy over the past several decades, the prognosis remains unfavorable with an overall 5-year survival rate below 15% in patients with lung cancer. 3,4 Poor prognosis and frequent relapses with patients with lung cancer urgently require the development of new screening and noninvasive biomarkers to predict lung cancer.Exosomes are small membrane vesicles and secreted by all types of cells with 30 to 150 nm in diameter of Liangyuan Chen and Pengju Cao contributed equally.

Differential Secretion of Angiopoietic Factors and Expression of MicroRNA in Umbilical Cord Blood from Healthy Appropriate-For-Gestational-Age Preterm and Term Newborns—in Search of Biomarkers of Angiogenesis-Related Processes in Preterm Birth

“…In the present study, we observed in our cohort of preterm newborns, the significant up-regulation of miR-7977 in UCB that might result in a decreased angiogenesis-supporting capacity of BM CD34+ cells in preterm gestation through the reduction of angiopoietic factor levels in blood, such as Angiopoietin-1. In the other study, Chen et al have demonstrated in in vitro experiments that miR-7977 expression might be an important modulator involved in the molecular mechanisms of cell cycle, proliferation, and apoptosis [75]. Hence, miR-7977 could play an important role in the disturbance of fetal angiogenesis.…”

Extracellular Vesicle-Associated miRNAs as a Biomarker for Lung Cancer in Liquid Biopsy

“…Serum exosomal miR-1246 was also shown to have an early diagnostic value in distinguishing NSCLC from healthy controls with an AUC value of 0.827, and an AUC value of 0.757 when discriminating between NSCLC and non-malignant respiratory diseases (Huang and Qu, 2020). miR-7977 was confirmed by Chen et al to be the miRNA with the highest fold change for upregulation in the serum exosomes of LA patients based on miRNA arrays (Chen et al, 2020). The diagnostic test showed that the AUC value of miR-7977 was 0.787 (Chen et al, 2020).…”

“…miR-7977 was confirmed by Chen et al to be the miRNA with the highest fold change for upregulation in the serum exosomes of LA patients based on miRNA arrays (Chen et al, 2020). The diagnostic test showed that the AUC value of miR-7977 was 0.787 (Chen et al, 2020). miR-98-3p was demonstrated to be the most dramatic downregulated miRNA, with an AUC value of 0.719 (Chen et al, 2020).…”

“…The diagnostic test showed that the AUC value of miR-7977 was 0.787 (Chen et al, 2020). miR-98-3p was demonstrated to be the most dramatic downregulated miRNA, with an AUC value of 0.719 (Chen et al, 2020). Another study regarding LA recruited three groups of patients comprising LA pre-and post-operation and healthy volunteers (Han et al, 2020).…”

Composition and Clinical Significance of Exosomes in Tuberculosis: A Systematic Literature Review

“…Serum exosomal miRNA-1290 represents a potential diagnostic and prognostic marker in patients with lung adenocarcinoma [133]. Serum exosomes could be a valuable source of diagnostically important exosomal miR-7977 for the diagnosis of lung cancer [134]. A study conducted by Ueda et al in 2014 identified CD91 as a lung adenocarcinoma specific antigen on exosomes [135].…”