Messenger-RNA Expression of Five Gemcitabine Sensitivity-related Genes Predicting Outcome in Advanced-stage Non-small Cell Lung Cancer.
CDA
Non-small cell lung carcinoma
RRM1
RRM2
dCK
gemcitabine
hENT1
messenger RNA
pharmacogenomics
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
03
12
2019
revised:
14
12
2019
accepted:
16
12
2019
entrez:
5
2
2020
pubmed:
6
2
2020
medline:
20
3
2020
Statut:
ppublish
Résumé
Tumoural transcriptional levels of RRM1, RRM2, CDA, dCK and hENT1 genes are potential biomarkers for gemcitabine's efficacy in non-small cell lung cancer (NSCLC). We retrospectively analysed each gene's relative mRNA expression by quantitative, real-time polymerase chain reaction in microdissected, formalin-fixed, paraffin-embedded primary-tumour specimens from 219 chemonaïve patients with advanced-stage NSCLC, treated with gemcitabine-based regimens within clinical trials. The five genes' transcriptional patterns were integrated into an ordinal, five-level gemcitabine-susceptibility classifier (5L-GSC). Treatment efficacy increased progressively across the five susceptibility levels, with the very-high chemosensitivity cases obtaining the most clinical benefit. 5L-GSC emerged as an independent prognosticator for overall response and disease control rates, time to progression and overall survival at p-values of 0.03, 0.004, <0.001 and <0.001, respectively, with results remaining significant after bootstrapping. Penalised, optimally-scaled, categorical-regression modelling of overall response identified 5L-GSC as the most stable predictor. The proposed composite biomarker is promising for customising front-line chemotherapy in NSCLC.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Tumoural transcriptional levels of RRM1, RRM2, CDA, dCK and hENT1 genes are potential biomarkers for gemcitabine's efficacy in non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS
METHODS
We retrospectively analysed each gene's relative mRNA expression by quantitative, real-time polymerase chain reaction in microdissected, formalin-fixed, paraffin-embedded primary-tumour specimens from 219 chemonaïve patients with advanced-stage NSCLC, treated with gemcitabine-based regimens within clinical trials. The five genes' transcriptional patterns were integrated into an ordinal, five-level gemcitabine-susceptibility classifier (5L-GSC).
RESULTS
RESULTS
Treatment efficacy increased progressively across the five susceptibility levels, with the very-high chemosensitivity cases obtaining the most clinical benefit. 5L-GSC emerged as an independent prognosticator for overall response and disease control rates, time to progression and overall survival at p-values of 0.03, 0.004, <0.001 and <0.001, respectively, with results remaining significant after bootstrapping. Penalised, optimally-scaled, categorical-regression modelling of overall response identified 5L-GSC as the most stable predictor.
CONCLUSION
CONCLUSIONS
The proposed composite biomarker is promising for customising front-line chemotherapy in NSCLC.
Identifiants
pubmed: 32014934
pii: 40/2/901
doi: 10.21873/anticanres.14023
doi:
Substances chimiques
RNA, Messenger
0
Deoxycytidine
0W860991D6
Gemcitabine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
901-913Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.