Dataset Information

Impact of ABCG2 polymorphisms on the clinical outcome of TKIs therapy in Chinese advanced non-small-cell lung cancer patients.

ABSTRACT:

Objective

The primary purpose of this study was to investigate the correlation between single nucleotide polymorphisms (SNPs) of ATP binding cassette superfamily G member 2 (ABCG2) and outcome of tyrosine kinase inhibitions (TKIs) therapy in Chinese advanced non-small-cell lung cancer (NSCLC) patients. The secondary objective was to identify biomarkers to evaluate the response to treatment and outcome of the targeted therapy.

Methods

SNP genotyping (34 G/A, 421 C/A, 1143 C/T and -15622 C/T) of ABCG2 gene in 100 patients was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The clinical characteristics of 100 patients were collected. A total of 70 patients were treated with TKIs (gefitinib, erlotinib and icotinib). The association between ABCG2 polymorphisms and clinical characteristics was evaluated. Kaplan-Meier survival curves were plotted for overall survival (OS) and analyzed with the log-rank test.

Results

The three polymorphisms of the ABCG2 34 G/A, 421 C/A and 1143 C/T occurred more frequently compared with -15622 C/T in Chinese advanced NSCLC patients. There was no association between ABCG2 polymorphisms and clinical characteristics (p > 0.05). The median OS of patients with GG genotype at position 34 of the ABCG2 gene was significantly shorter than those with GA or AA genotype (p < 0.05). No significant difference of OS was found in 421 C/A and 1143 C/T polymorphisms (p > 0.05).

Conclusion

ABCG2 34 G/A may be a possible predictor of the clinical outcome of TKIs therapy in NSCLC patients.

SUBMITTER: Chen X

PROVIDER: S-EPMC4425882 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of ABCG2 polymorphisms on the clinical outcome of TKIs therapy in Chinese advanced non-small-cell lung cancer patients.

Chen Xueqin X Chen Dadong D Yang Shaoyu S Ma Ruobing R Pan Yuelong Y Li Xin X Ma Shenglin S

Cancer cell international 20150419

<h4>Objective</h4>The primary purpose of this study was to investigate the correlation between single nucleotide polymorphisms (SNPs) of ATP binding cassette superfamily G member 2 (ABCG2) and outcome of tyrosine kinase inhibitions (TKIs) therapy in Chinese advanced non-small-cell lung cancer (NSCLC) patients. The secondary objective was to identify biomarkers to evaluate the response to treatment and outcome of the targeted therapy.<h4>Methods</h4>SNP genotyping (34 G/A, 421 C/A, 1143 C/T and - ...[more]

PMID: 25960692

Similar Datasets

Project description:BackgroundThe prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- mutated advanced non-small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments.MethodsEligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.ResultsIn total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR = 1.88, 95%CI: 1.59-2.23, p < 0.001, I2 = 0.0%, P = 0.792) and overall survival (OS) (HR = 1.92, 95%CI: 1.55-2.38, p < 0.001, I2 = 0.0%, P = 0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P < 0.001, I2 = 0.0%, P = 0.473; pooled HR for OS: 1.94, 95% CI 1.36-2.76, P < 0.001, I2 = 0.0%, P = 0.484). Begg's funnel plots and Egger's tests indicated no significant publication bias in this study.ConclusionsThis meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced NSCLC.

Project description:PurposeTo identify non-cancerous factors from baseline CT chest affecting survival in advanced non-small cell lung cancer (NSCLC) treated with first-generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs).MethodsRetrospective study of 172 advanced NSCLC patients treated with first-generation EGFR-TKIs as a first-line systemic treatment (January 2012 to September 2022). Baseline CT chest assessed visceral/subcutaneous fat (L1 level), sarcopenia, and myosteatosis (multiple levels), main pulmonary artery (MPA) size, MPA to aorta ratio, emphysema, and bone mineral density. Cox regression analyzed prognostic factors at 18-month outcome.ResultsMedian overall survival was 17.57 months (14.87-20.10) with 76 (44.19%) patients died at 18 months. Deceased had lower baseline BMI (21.10 ± 3.44) vs. survived (23.25 ± 4.45) (p < 0.001). Univariable analysis showed 5 significant prognostic factors: low total adiposity with/without cutoff [HR 2.65 (1.68-4.18), p < 0.001; 1.00 (0.99-1.00), p = 0.006;], low subcutaneous adipose tissue (SAT) with/without cutoff [HR 1.95 (1.23-3.11), p = 0.005; 0.99 (0.98-0.99), p = 0.005], low SAT index (SATI) with/without cutoff [1.74 (1.10-2.78), p = 0.019; 0.98 (0.97-0.99), p = 0.003], high VSR [1.67 (1.06-2.62), p = 0.026], and high MPA size with/without cutoff [2.23 (1.23-4.04), p = 0.005; 1.09 (1.04-1.16), p = 0.001]. MPA size, MPA size > 29 mm, and total adiposity ≤85 cm2 remained significant in multivariable analysis, adjusted by BMI [HR 1.14 (1.07-1.21), p < 0.001; 3.10 (1.81-5.28), p < 0.001; 3.91 (1.63-9.40), p = 0.002]. There was no significant difference of sarcopenic and myosteatotic parameters between the two groups.ConclusionIn advanced EGFR-mutated NSCLC patients, assessing pre-treatment prognosis is warranted to predict the survival outcome and guide decision regarding EGFR-TKI therapy. Enlarged MPA size, low total adiposity, and low subcutaneous fat (lower SAT, lower SATI, and higher VSR) are indicators of poor survival. Large MPA size (>29 mm) or low total adiposity (≤85 cm2) alone predict 18-month death.

Dataset Information

Impact of ABCG2 polymorphisms on the clinical outcome of TKIs therapy in Chinese advanced non-small-cell lung cancer patients.

Objective

Methods

Results

Conclusion

Publications

Impact of ABCG2 polymorphisms on the clinical outcome of TKIs therapy in Chinese advanced non-small-cell lung cancer patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets