Τίτλος:
Predicting the role of dna polymerase β alone or with kras mutations in advanced nsclc patients receiving platinum-based chemotherapy
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Clinical data suggest that only a subgroup of non-small cell lung cancer (NSCLC) patients has long-term benefits after front-line platinum-based therapy. We prospectively investigate whether KRAS status and DNA polymerase β expression could help identify patients responding to platinum compounds. Prospectively enrolled, advanced NSCLC patients treated with a first-line regimen containing platinum were genotyped for KRAS and centrally evaluated for DNA polymerase β expression. Overall survival (OS), progression-free survival (PFS), and the objective response rate (ORR) were recorded. Patients with KRAS mutations had worse OS (hazard ratio (HR): 1.37, 95% confidence interval (95% CI): 0.70–2.27). Negative DNA polymerase β staining identified a subgroup with worse OS than patients expressing the protein (HR: 1.43, 95% CI: 0.57–3.57). The addition of KRAS to the analyses further worsened the prognosis of patients with negative DNA polymerase β staining (HR: 1.67, 95% CI: 0.52–5.56). DNA polymerase β did not influence PFS and ORR. KRAS may have a negative role in platinum-based therapy responses in NSCLC, but its impact is limited. DNA polymerase β, when not expressed, might indicate a group of patients with poor outcomes. KRAS mutations in tumors not expressing DNA polymerase β further worsens survival. Therefore, these two biomarkers together might well identify patients for whom alternatives to platinum-based chemotherapy should be used. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Alvisi, M.F.
Ganzinelli, M.
Linardou, H.
Caiola, E.
Russo, G.L.
Cecere, F.L.
Bettini, A.C.
Psyrri, A.
Milella, M.
Rulli, E.
Fabbri, A.
De Maglie, M.
Romanelli, P.
Murray, S.
Ndembe, G.
Broggini, M.
Garassino, M.C.
Marabese, M.
Περιοδικό:
Journal of Clinical Medicine Research
Λέξεις-κλειδιά:
biological marker; carboplatin; cisplatin; DNA directed DNA polymerase beta; gemcitabine; K ras protein; pemetrexed; platinum derivative; vinorelbine tartrate, adult; aged; Article; cancer prognosis; chemoradiotherapy; controlled study; DNA extraction; female; gene mutation; genetic analysis; genotype; histology; human; human tissue; immunohistochemistry; major clinical study; male; multicenter study; non small cell lung cancer; overall survival; polymerase chain reaction; progression free survival; prospective study; protein expression; Sanger sequencing
