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Distinct Angiogenic microRNA-mRNA Expression Profiles Among Subtypes of Lung Adenocarcinoma

  • Original Article
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Pathology & Oncology Research

Abstract

Adenocarcinoma (ADC) represents the most common histological type of non-small cell lung cancer (NSCLC), with a heterogeneous pattern of growth classified as lepidic, acinar, papillary, solid, and micropapillary. For ADC patients there are few available therapeutic options and a valuable therapeutic strategy is represented by angiogenesis inhibitors; however, new reliable biomarkers to identify patients with benefit from anti-angiogenic drugs are needed. We designed a panel of sixteen miRNAs together with six their mRNA targets involved in the angiogenesis pathway and expression analysis was performed by the nCounter System® (NanoString Technologies) in 88 ADC patients: 29 were predominantly lepidic (33%), 26 solid (29.5%), 22 acinar (25%), and for 11 patients the prevalent pattern was papillary (12.5%). When we compared mRNA expression levels with the different histological ADC subtypes we found a significant higher expression of VEGF in papillary and solid than in other subtypes (p = 0.008). Among 16 miRNAs that target the angiogenic mRNA, 4 were significantly downregulated in papillary/solid compared to other groups. Our data suggest a distinct angiogenic miRNA-mRNA expression profile among the subtypes of ADC, with a putative clinical application to stratify patients for anti-angiogenetic drugs. Moreover, the regulation of angiogenic mRNA factors by miRNAs could provide a novel therapeutic approach based on their expression pattern specific for distinct ADC subtypes. Further studies are needed in a larger cohort of patients to confirm our results.

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Authors and Affiliations

  1. Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Via Roma 57, 56126, Pisa, Italy

    Laura Boldrini, Mirella Giordano, Franca Melfi, Marco Lucchi & Gabriella Fontanini

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  1. Laura Boldrini
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  2. Mirella Giordano
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  3. Franca Melfi
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  4. Marco Lucchi
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  5. Gabriella Fontanini
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Contributions

Laura Boldrini, Mirella Giordano and Gabriella Fontanini conceived and designed the experiments; Mirella Giordano performed the experiments; Laura Boldrini wrote the paper; Gabriella Fontanini diagnosed lung cancer; Franca Melfi, and Marco Lucchi performed lung surgery.

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Correspondence to Laura Boldrini.

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Our study was conducted in accordance with the ethical standards of our institutional research committee and with the 1964 Helsinki declaration.

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Boldrini, L., Giordano, M., Melfi, F. et al. Distinct Angiogenic microRNA-mRNA Expression Profiles Among Subtypes of Lung Adenocarcinoma. Pathol. Oncol. Res. 26, 1089–1096 (2020). https://doi.org/10.1007/s12253-019-00664-7

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  • DOI: https://doi.org/10.1007/s12253-019-00664-7

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