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Association of BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA expression levels between primary tumors and infiltrated regional lymph nodes in patients with resectable non-small cell lung cancer

The Pharmacogenomics Journal volume 19, pages 15–24 (2019)Cite this article

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Abstract

Differences in gene expression levels between the primary tumors (PTs) and matched regional lymph nodal metastases (LNs) in patients with totally excised non-small cell lung cancer (NSCLC) were explored. Microdissected formalin-fixed paraffin-embedded (FFPE) samples from (PT) and their matched infiltrated LNs, from 239 patients [183 (with matched PT and LNs samples)-case and 56 PT only samples-control cohorts] were analyzed for BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA expression by quantitative real-time polymerase-chain reaction (PCR). Moderately positive correlation between the expression of each gene in the PT and the matched LNs was observed. Concordance rates between the PT and the LNs were: BRCA1 (67.7%), ERCC1 (68.4%), PKM2 (63.4%), RAP80 (68.8%), RRM1 (70.9%), RRM2 (69%), TS (72.9%), TSP1 (69.8%), TXR1 (63.7%). Expression levels and their differences were correlated with Relapse-Free Survival (RFS) and Overall Survival (OS). High BRCA1 PT in patients with squamous histology was associated with increased OS (p = 0.036). High TSP1 PT levels were shown to be the only independent prognostic factor for OS and RFS (p = 0.023 and p = 0.007). PKM2 low levels in both PT and matched LNs were associated with better OS irrespective of the underlying histology (p = 0.031). RRM1 discordant levels between PT and matched LNs were associated with worse OS in squamous tumors (p = 0.019) compared to patients with both low expression in PT and LN.TXR1 high levels in both PT and matched LNs were associated with better OS in patients with squamous tumors (p = 0.007).These findings indicate that there is different gene expression between PT and matched LNs which may affect the outcome in early NSCLC and therefore PT’s molecular biology should not be the sole determinant for prognostication.

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Acknowledgements

This work was partially supported by Cretan Association for Biomedical Research (CABR), the Hellenic Society of Medical Oncology (HESMO) and the EORTC-Cancer Research Fund.

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Authors and Affiliations

  1. EORTC, Headquarters, Brussels, Belgium

    K Tryfonidis, S Assele & B Hasan

  2. Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece

    K Tryfonidis, C Papadaki,  M Trypaki, E Tsakalaki, M Sfakianaki, V Georgoulias & J Souglakos

  3. Department of Pathology, University of Crete, Heraklion, Greece

    E Lagoudaki, A Koutsopoulos & E Stathopoulos

  4. Institute Gustave Roussy, Paris, France

    J Menis

  5. EORTC Lung Cancer Group, EORTC Headquarters, Brussels, Belgium

    J Menis

  6. School of Medicine, University of Crete, Heraklion, Crete, Greece

    V Georgoulias

  7. Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece

    J Souglakos

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  1. K Tryfonidis
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Correspondence to K Tryfonidis.

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Tryfonidis, K., Papadaki, C., Assele, S. et al. Association of BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA expression levels between primary tumors and infiltrated regional lymph nodes in patients with resectable non-small cell lung cancer. Pharmacogenomics J 19, 15–24 (2019). https://doi.org/10.1038/s41397-018-0013-9

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