Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum

Abstract

Abstract. Pemetrexed combined with platinum is a first-line therapy used to treat patients with advanced non-small cell lung cancer (NSCLC) that exhibit negative or unknown epidermal growth factor receptor (EGFR) mutational status or anaplastic lymphoma kinase (ALK) rearrangements. Lung adenocarcinoma (LAC) is the primary type of NSCLC. In order to prevent overtreatment, it is necessary to identify patients with LAC who may not benefit from certain chemotherapies. Patients recruited in the present study (n=129) were diagnosed with advanced LAC and received first-line pemetrexed and platinum-based chemotherapy. A microRNA (miR) microarray was used to screen the plasma miR expression profiles in a screening set of eight patients prior to and following treatment. Specifically, plasma miR-25, miR-21, miR-27b, miR-326, miR-483-5p and miR-920 were selected for reverse transcription-quantitative polymerase chain reaction analysis in a training set (n=44) prior to treatment. The screening and training set patients were all non-smokers with no prior history of serious or chronic disease. The ∆∆Cq values of these miRs were compared between the group that showed benefit from pemetrexed and platinum treatment and the group that did not. Consequently, the ∆∆Cq values of miR-25, miR-21, miR-27b and miR-326 were further determined in a validation set (n=77). The results of the present study demonstrate that plasma expression levels of miR-25, miR-21, miR-27b and miR-326, in the training and validation sets prior to treatment, were significantly different between the benefit and non-benefit groups (P≤0.001). The expression of miR-25, miR-21, miR-27b and miR-326 was upregulated in the non-benefit group and this elevation was positively correlated with decreased progression-free survival (PFS; P≤0.001). In addition, the predictive power of each miR was evaluated through receiver operating characteristic curves, in which miR-25 exhibited the highest degree of accuracy (area under the curve, 0.926; 95% confidence interval, 0.881-0.971). These results indicate that overexpression of plasma miR-25, miR-21, miR-27b and miR-326, prior to treatment, in patients with advanced LAC is predictive of non-benefit from first-line pemetrexed and platinum-based chemotherapy, and is associated with decreased PFS. Among these four miRs, miR-25 exhibited the highest degree of accuracy in predicting insensitivity, suggesting it is the most promising biomarker.

Diagnostic biomarker and therapeutic target applications of miR‐326 in cancers: A systematic review

“…Zhu et al (2016) on 129 participants, it was noticed that miR-25, miR-21, miR-27b and miR-326 can consider as the most promising biomarker for LAC (J. Zhu et al, 2016). MiR-326 upregulates epithelial-to-mesenchymal transition (EMT)-induced cells invasion in LAC by targeting of ADAM17 (Cai et al, 2015).…”

A Large Set of miRNAs Is Dysregulated from the Earliest Steps of Human Hepatocellular Carcinoma Development

“…Finally, miR-21 is up-regulated not only in HCC but also in precursor lesions. It has been previously reported that miR-21 is up-regulated in HCC tissues and hepatoma cell lines, 29,37 and that its expression gradually increases along with an augmented invasive phenotype of the tumor. Moreover, miR-21 has been reported to play a role in hepatocyte proliferation by promoting cyclin D1 translation and inhibition of tumor suppressor genes (eg, phosphatase and tensin homolog) and apoptotic genes (programed cell death 4 and B-cell lymphoma 2).…”

Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands

“…Also, miR-483-3p reversed EMT and repressed migration, invasion, and metastasis of GR NSCLC cells. Mechanistically, miR-483-3p directly targeted integrin β3, consequently inhibiting the downstream FAK/Erk signaling pathway, highlighting miR-483-3p is a prospective target for combination treatment to overcome acquired EGFR TKI resistance in EGFR-mutant NSCLC [226,227]. miR-625-3p can potentially target AXL receptor tyrosine kinase, and this miRNA expression is markedly decreased in the HCC827GR cell line, while its overexpression partly reversed gefitinib resistance.…”