KRAS mutation and DNA repair and synthesis genes in non‑small‑cell lung cancer

Ludovini,Vienna; Ricciuti,Biagio; Tofanetti,Francesca R.; Mencaroni,Clelia; Giannarelli,Diana; Sidoni,Angelo; Reda,Maria S.; Siggillino,Annamaria; Baglivo,Sara; Crinò,Lucio; Bellezza,Guido; Chiari,Rita; Metro,Giulio

doi:10.3892/mco.2018.1731

KRAS mutation and DNA repair and synthesis genes in non‑small‑cell lung cancer

Authors:
- Vienna Ludovini
- Biagio Ricciuti
- Francesca R. Tofanetti
- Clelia Mencaroni
- Diana Giannarelli
- Angelo Sidoni
- Maria S. Reda
- Annamaria Siggillino
- Sara Baglivo
- Lucio Crinò
- Guido Bellezza
- Rita Chiari
- Giulio Metro
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Affiliations: Department of Medical Oncology, Santa Maria della Misericordia Hospital, AOU di Perugia, I‑06129 Perugia, Italy, Department of Medical Oncology 1, Regina Elena National Cancer Institute, IRCCS, I‑00144 Rome, Italy, Department of Experimental Medicine, Division of Pathology and Histology, University of Perugia Medical School, I‑06129 Perugia, Italy, Department of Medical Oncology, Scientific Institute Romagnolo for The Study and Treatment of Tumors, I‑47014 Meldola (FC), Italy
Published online on: October 1, 2018 https://doi.org/10.3892/mco.2018.1731
Pages: 689-696

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Abstract

The aim of the present study was to assess the expression of select DNA repair and synthesis genes in non-small-cell lung cancer (NSCLC) according to KRAS mutation status. ERCC1, TS, RRM1, and BRCA1 mRNA expression levels were assessed from either primary or metastatic tumor specimens of patients diagnosed with epidermal growth factor receptor (EGFR) wild‑type (WT) advanced NSCLC. Total RNA was isolated from paraffin‑embedded tumor specimens using the RNeasy FFPE kit and automatically purified using a QiaCube instrument. Quantification levels were analyzed by real‑time one‑step RT‑PCR using QuantiFast technology, and the results were compared considering β‑actin as the internal reference gene. One hundred and eighty‑four patients with advanced NSCLC were evaluated for the analysis, of which 92 were KRAS‑mutants. Nearly all patients had adenocarcinoma histology (96.7%). Among KRAS‑mutants, the majority had a KRAS codon 12 mutation (88%), the most common being G12C (44.4% of cases). Mean ERCC1 levels were indicated to be significantly higher in KRAS‑mutants when compared with KRAS WT patients (3,234±6.63 vs. 184±1.24; P=0.05). However, mean TS levels were significantly lower in the KRAS‑mutant subgroup compared with the KRAS WT subgroup (4,481±3.756 vs. 5,941±6.4; P=0.039). KRAS‑mutant NSCLCs are more likely to express high ERCC1 and low TS levels. This finding may suggest different sensitivity to cytotoxic chemotherapy according to KRAS mutation status.

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