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

  • Authors:
    • Jinghua Zhu
    • Yuhua Qi
    • Jianzhong Wu
    • Meiqi Shi
    • Jifeng Feng
    • Longbang Chen

  • View Affiliations

  • Published online on: October 19, 2016     https://doi.org/10.3892/ol.2016.5295
  • Pages: 4829-4837
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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.
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December-2016
Volume 12 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • Journal Metrics
  • Impact Factor: 2.9
  • Ranked Oncology
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  • CiteScore: 6.3
  • CiteScore Rank: Q2: #119/366 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.725
  • SCImago Journal Rank (SJR): 0.639
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Spandidos Publications style
Zhu J, Qi Y, Wu J, Shi M, Feng J and Chen L: Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum. Oncol Lett 12: 4829-4837, 2016
APA
Zhu, J., Qi, Y., Wu, J., Shi, M., Feng, J., & Chen, L. (2016). Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum. Oncology Letters, 12, 4829-4837. https://doi.org/10.3892/ol.2016.5295
MLA
Zhu, J., Qi, Y., Wu, J., Shi, M., Feng, J., Chen, L."Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum". Oncology Letters 12.6 (2016): 4829-4837.
Chicago
Zhu, J., Qi, Y., Wu, J., Shi, M., Feng, J., Chen, L."Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum". Oncology Letters 12, no. 6 (2016): 4829-4837. https://doi.org/10.3892/ol.2016.5295