RGD Reference Report - Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients. - Rat Genome Database

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Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.

Authors: Boukovinas, Ioannis  Papadaki, Chara  Mendez, Pedro  Taron, Miquel  Mavroudis, Dimitris  Koutsopoulos, Anastasios  Sanchez-Ronco, Maria  Sanchez, Jose Javier  Trypaki, Maria  Staphopoulos, Eustathios  Georgoulias, Vassilis  Rosell, Rafael  Souglakos, John 
Citation: Boukovinas I, etal., PLoS One. 2008;3(11):e3695. doi: 10.1371/journal.pone.0003695. Epub 2008 Nov 11.
RGD ID: 127229933
Pubmed: PMID:19002265   (View Abstract at PubMed)
PMCID: PMC2579656   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0003695   (Journal Full-text)


BACKGROUND: Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. We have retrospectively examined the effect of RRM1, RRM2 and BRCA1 expression on outcome to gemcitabine plus docetaxel in advanced non-small-cell lung cancer (NSCLC) patients.
METHODOLOGY AND PRINCIPAL FINDINGS: Tumor samples were collected from 102 chemotherapy-naïve advanced NSCLC patients treated with gemcitabine plus docetaxel as part of a randomized trial. RRM1, RRM2 and BRCA1 mRNA levels were assessed by quantitative PCR and correlated with response, time to progression and survival. As BRCA1 levels increased, the probability of response increased (Odds Ratio [OR], 1.09: p = 0.01) and the risk of progression decreased (hazard ratio [HR], 0.99; p = 0.36). As RRM1 and RRM2 levels increased, the probability of response decreased (RRM1: OR, 0.97; p = 0.82; RRM2: OR, 0.94; p<0.0001) and the risk of progression increased (RRM1: HR, 1.02; p = 0.001; RRM2: HR, 1.005; p = 0.01). An interaction observed between BRCA1 and RRM1 allowed patients to be classified in three risk groups according to combinations of gene expression levels, with times to progression of 10.13, 4.17 and 2.30 months (p = 0.001). Low BRCA1 expression was the only factor significantly associated with longer time to progression in 31 patients receiving cisplatin-based second-line therapy.
CONCLUSIONS: The mRNA expression of BRCA1, RRM1 and RRM2 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy and warrants further investigation in prospective studies.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Rrm1  (ribonucleotide reductase catalytic subunit M1)
Rrm2  (ribonucleotide reductase regulatory subunit M2)

Genes (Mus musculus)
Rrm1  (ribonucleotide reductase M1)
Rrm2  (ribonucleotide reductase M2)

Genes (Homo sapiens)
RRM1  (ribonucleotide reductase catalytic subunit M1)
RRM2  (ribonucleotide reductase regulatory subunit M2)


Additional Information