Dataset Information

Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy.

ABSTRACT: BACKGROUND:The aim of this study was to investigate prognostic value of excision repair cross-complementing 1 (ERCC1), BCL2-associated athanogene (BAG-1), the breast and ovarian cancer susceptibility gene 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and class III ?-tubulin (TUBB3) in patients with non-small cell lung cancer (NSCLC) who received platinum- based adjuvant chemotherapy. METHODS:Messenger RNA expressions of these genes were examined in 85 tumor tissues and 34 adjacent tissue samples using semi-quantitative RT-PCR. The expressions of these five genes were analyzed in relation to chemotherapy and progression-free survival (PFS) and overall survival (OS). Seventy-four patients were enrolled into chemotherapy. RESULTS:Patients with ERCC1 or BAG-1 negative expression had a significantly longer PFS (P = 0.001 and P = 0.001) and OS (P = 0.001 and P = 0.001) than those with positive expression. Patients with negative ERCC1 and BAG-1 expression benefited more from platinum regimen (P = 0.001 and P = 0.002). Patients with BRCA1 negative expression might have a longer OS (P = 0.052), but not PFS (P = 0.088) than those with BRCA1 positive expression. A significant relationship was observed between the mRNA expression of ERCC1 and BAG-1 (P = 0.042). In multivariate analysis, ERCC1 and BAG-1 were significantly favorable factors for PFS (P = 0.018 and P = 0.017) and OS (P = 0.027 and P = 0.022). CONCLUSIONS:ERCC1 and BAG-1 are determinants of survival after surgical treatment of NSCLC, and its mRNA expression in tumor tissues could be used to predict the prognosis of NSCLC treated by platinum.

SUBMITTER: Leng XF

PROVIDER: S-EPMC3338093 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy.

Leng Xue-Feng XF Chen Ming-Wu MW Xian Lei L Dai Lei L Ma Guang-Yao GY Li Man-Hong MH

Journal of experimental & clinical cancer research : CR 20120323

<h4>Background</h4>The aim of this study was to investigate prognostic value of excision repair cross-complementing 1 (ERCC1), BCL2-associated athanogene (BAG-1), the breast and ovarian cancer susceptibility gene 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and class III β-tubulin (TUBB3) in patients with non-small cell lung cancer (NSCLC) who received platinum- based adjuvant chemotherapy.<h4>Methods</h4>Messenger RNA expressions of these genes were examined in 85 tumor tissues and 34 ...[more]

PMID: 22439756

Similar Datasets

Project description:BackgroundGenetic testing is widespread among breast cancer patients; however, no guideline recommends using germline genetic testing results to select a chemotherapy regimen. It is unknown whether breast cancer patients who carry pathogenic variants (PVs) in BRCA1 and/or 2 (BRCA1/2) or other cancer-associated genes receive different chemotherapy regimens than noncarriers.MethodsWe linked Surveillance, Epidemiology, and End Results registry records from Georgia and California to germline genetic testing results from 4 clinical laboratories. Patients who 1) had stages I-III breast cancer, either hormone receptor (HR) positive and HER2 negative or triple negative (TNBC), diagnosed in 2013-2017; 2) received chemotherapy; and 3) were linked to genetic results were included. Chemotherapy details were extracted from Surveillance, Epidemiology, and End Results text fields completed by registrars. We examined whether PV carriers received more intensive regimens (HR-positive,HER2-negative: ≥3 drugs including an anthracycline; TNBC: ≥4 drugs including an anthracycline and platinum) and/or less standard breast cancer agents (a platinum). All statistical tests were 2-sided.ResultsAmong 2293 patients, 1451 had HR-positive, HER2-negative disease, and 842 had TNBC. On multivariable analysis of women with HR-positive, HER2-negative disease, receipt of a more intensive chemotherapy regimen varied statistically significantly by genetic results (P = .02), with platinum receipt more common among BRCA1/2 PV carriers (odds ratio = 2.44, 95% confidence interval = 1.36 to 4.38; P < .001). Among women with TNBC, chemotherapy agents did not vary significantly by genetic results.ConclusionBRCA1/2 PV carriers with HR-positive, HER2-negative breast cancer had twofold higher odds than noncarriers of receiving a platinum, as part of a more intensive chemotherapy regimen. This likely represents overtreatment and emphasizes the need to monitor how genetic testing results are managed in oncology practice.

Project description:BackgroundExcision repair cross complementing 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) are molecular determinants that predict sensitivity or resistance to platinum agents and gemcitabine, respectively. Tailored therapy using these molecular determinants suggested patient benefit in a previously reported phase 2 trial. Here, we report an individual patient analysis of prospectively accrued patients who were treated with the "personalized therapy" approach versus other "standard," noncustomized approaches.MethodsPatients who had nonsmall cell lung cancer (NSCLC) with extranodal metastatic disease and an Eastern Cooperative Oncology Group performance status of 0/1 were accrued to 4 phase 2 clinical trials conducted at the H. Lee Moffitt Cancer Center: Trial A (first-line carboplatin/gemcitabine followed by docetaxel), Trial B (docetaxel and gefitinib in patients aged ≥70 years), Trial C (combination therapy with carboplatin/paclitaxel/atrasentan), and Trial D (personalized therapy based on ERCC1 and RRM1 expression). Patients with low RRM1/low ERCC1 expression received gemcitabine/carboplatin, patients with low RRM1/high ERCC1 expression received gemcitabine/docetaxel, patients with high RRM1/low ERCC1 expression received docetaxel/carboplatin, and patients with high RRM1/high ERCC1 expression received vinorelbine/docetaxel. Patients who were treated on Trials A, B, and C were pooled together and analyzed as the "standard therapy" group. Patients accrued to Trial D were called the "personalized therapy" group. Individual patient data were updated as of February 8, 2011. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.ResultsThere were statistically significant improvements between the personalized therapy group versus the standard therapy group in response (44% vs 22%; P = .002), OS (median: 13.3 months vs 8.9 months; P = .016), and PFS (median: 7.0 months vs 4.3 months; P = .03).ConclusionsThe results from individual patient analyses suggest that ERCC1 and RRM1/tailored selection of first-line therapy improved survival over standard treatment-selection approaches.

Project description:BackgroundAmong patients with stage I breast cancer, there is significant uncertainty concerning the optimal threshold at which to consider chemotherapy, and when considered, there is controversy regarding whether to consider non-intensive versus intensive regimens. The authors examined the types and costs of adjuvant chemotherapy received among patients with stage I breast cancer.MethodsThe current study was a prospective cohort study including patients with stage I breast cancer who were treated at a National Comprehensive Cancer Network center from 2000 through 2009. Stage was defined according to the version of the American Joint Committee on Cancer Staging Manual applicable at the time of diagnosis. Stratifying by human epidermal growth factor receptor 2 (HER2), the authors examined the percentage of patients receiving intensive versus non-intensive chemotherapy regimens and the factors associated with type of chemotherapy administered using multivariable logistic regression. Costs of the most common regimens were estimated.ResultsOf 8907 patients, 33% received adjuvant chemotherapy. Among those individuals, there was an increase in the use of intensive chemotherapy within the last decade, from 31% in 2000 through 2005 to 63% in 2008 through 2009 (including an increase in the use of the combination of docetaxel, carboplatin, and trastuzumab) among patients with HER2-positive disease and from 15% in 2000 through 2005 to 41% in 2008 through 2009 among patients with HER2-negative disease (32% of patients with hormone receptor-positive and 59% of patients with triple-negative disease). Among patients treated with non-intensive regimens, there was an increase in the use of the combination of docetaxel and cyclophosphamide noted, with a decrease in the use of the doxorubicin and cyclophosphamide combination. The choice of regimen varied significantly by institution. The major drivers of cost variation were the incorporation of biologics (eg, trastuzumab) and growth factors, with significant variation even within non-intensive and intensive regimens.ConclusionsOver time, there was an increase in use of intensive regimens among Stage I breast cancer, with striking institutional and cost variations.

Dataset Information

Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy.

Publications

Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets