Circulating miR-22, miR-24 and miR-34a as novel predictive biomarkers to pemetrexed-based chemotherapy in advanced non small cell lung cancer

Abstract

Pemetrexed has been widely used in patients with advanced non-small cell lung cancer (NSCLC). The clinical relevance of polymorphisms of folate pathway genes for pemetrexed metabolism have not been fully elucidated yet. The aim of this study was to evaluate the expression levels of circulating miR-22, miR-24, and miR-34a, possibly involved in folate pathway, in NSCLC patients treated with pemetrexed compared with healthy controls and to investigate their impact on patient clinical outcomes. A total of 22 consecutive patients with advanced NSCLC, treated with pemetrexed-based chemotherapy and 27 age and sex matched healthy controls were included in this preliminary analysis. miR-22, miR-24, and miR-34a targets were identified by TargetScan 6.2 algorithm, validating the involvement of these microRNAs in folate pathway. MicroRNAs were isolated from whole blood and extracted with miRNAeasy Mini Kit (Qiagen). miRNA profiling was performed using Real-Time PCR. SPSS 17 was used to data analysis. miR-22, miR-24, and miR-34a were found upregulated (P < 0.05) in NSCLC patients versus healthy controls. Higher expression levels were recorded for miR-34a. Nevertheless, significantly higher miR-22 expression was observed in patients developing progressive disease (P ¼ 0.03). No significant associations with clinical outcome were recorded for miR-24 and miR-34a. Albeit preliminary, these data support the involvement of miR-22, miR-24, and miR-34a in advanced NSCLC. The correlation between high expression of miR-22 in whole blood and the lack of response in pemetrexed treated NSCLC patients indicates that miR-22 could represent a novel predictive biomarker for pemetrexed-based treatment.J. Cell. Physiol. 229: 97-99, 2014. ß 2013 Wiley Periodicals, Inc.Despite significant improvements in the treatment of non-small cell lung cancer (NSCLC) over the past several years, the prognosis for patients with advanced disease remains poor. Chemotherapy resistance is a key contributor to the dismal prognoses for lung cancer patients.However, important advances have been achieved in the treatment of advanced NSCLC with the introduction of new antiblastic and biological agents.Lung cancer is driven by genomic alterations, and cancer cells use multiple mechanisms to alter the activity of key genes: mutation, amplification, deletion, intrachromosomal and interchromosomal translocation, and epigenetic mechanisms (MacConaill, 2012).The progresses in the field of genomics during the past decade have greatly advanced our understanding of the genomic alterations that contribute to lung cancer, but additional challenges must be addressed before the goal of personalized cancer therapy can become a reality for lung cancer patients.Pemetrexed, a chemotherapeutic agent already approved in the second-line setting (Hanna et al., 2004), has demonstrated its efficacy also in the first-line treatment combined with cisplatin (Scagliotti et al., 2008) and in the maintenance treatment as single-agent in non-squamous NSCLC (Ciuleanu et al., 2009;Paz-Ares et al., ...

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

“…Expression of the miR-34 family was downregulated in tumor tissue compared with normal tissue, and low levels of miR-34a expression were associated with a higher probability of relapse in surgically resected NSCLC (28). However, higher levels of circulating miR-34a were observed in patients with NSCLC compared with healthy controls (29). Higher levels of miR-34a indicated a shorter OS time in patients receiving palliative platinum derivate-based chemotherapy in combination with gemcitabine in the present study.…”

MicroRNAs: A Puzzling Tool in Cancer Diagnostics and Therapy

“…Likely to cellular miRNAs, studies suggested that changes in the profile of circulating miRNAs are correlated with a pathophysiological condition of human cancer. In line with this concept, data achieved from our studies indicated that blood levels of miR-22, miR-24 and miR-34a are correlated with advanced stages of non-small cell lung cancer (NSCLC) (25). Also, several other cell-free miRNAs (e.g.…”

Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer

“…It inhibits cell cycle progression by repressing Max and ErbB3 expression post-transcriptionally, mediates the effects of the tumor-suppressor p53, and suppresses interferon gene expression by blocking interferon regulatory factor-5 [49][50][51] . MiR-22 has been proposed as a potential serum marker for non-small cell lung cancer [52] , esophageal squamous cell carcinoma [53] , and nasopharyngeal carcinoma [54] . Our experimental strategy in this study focused on using hybridization-based microarray technology as the means to screen thousands of genes simultaneously, but it is also severely limited due to its issues with reproducibility and its tendency to produce a high rate of false positive and false negative results.…”