Dataset Information

Evaluation of Clinical and Genetic Determinants of Treatment OutCome In EGFR Mutation Positive Advanced Lung Adenocarcinoma.

ABSTRACT:

Background

The aim of this research was to evaluate clinical and low-cost genetic determinants of treatment outcome in EGFR mutation positive advanced lung adenocarcinoma patients.

Material and methods

EGFR mutation testing and EGFR 181946C>T genotyping were performed in 101 advanced lung adenocarcinoma patients using qRT-PCR and PCR-RFLP, respectively. Progression-free survival was defined as the time from the start of TKI therapy to date of progression, and overall survival as the time from diagnosis to death from any cause. Pain level was evaluated using a Numerical Rating Scale and the Verbal Descriptor Scale. Statistical significance was considered for P < .05.

Results

Patients were treated with EGFR-TKIs for a period of 1-39months (median 9), with a median PFS of 12.0 months (10.4-13.6, CI 95%), and a median OS of 19.0 months (15.1-22.7, CI 95%). The presence of pain was significantly correlated with the existence of bone (P < .001) and adrenal glands metastases (P = .029). Genetic factors did not have a direct impact on pain management but had a significant effect on the response to TKIs leading to pain alleviation.

Conclusions

EGFR mutation subtype and the EGFR 181946 C>T SNP had a significant effect on the response to TKI inducing an indirect anti-dolorous effect.

SUBMITTER: Jokic V

PROVIDER: S-EPMC9358214 | biostudies-literature | 2022 Jul-Sep

REPOSITORIES: biostudies-literature

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Publications

Evaluation of Clinical and Genetic Determinants of Treatment OutCome In EGFR Mutation Positive Advanced Lung Adenocarcinoma.

Jokic Vera V Savic-Vujovic Katarina K Spasic Jelena J Bukumiric Zoran Z Marinkovic Mladen M Radosavljevic Davorin D Cavic Milena M

Dose-response : a publication of International Hormesis Society 20220701 3

<h4>Background</h4>The aim of this research was to evaluate clinical and low-cost genetic determinants of treatment outcome in <i>EGFR</i> mutation positive advanced lung adenocarcinoma patients.<h4>Material and methods</h4><i>EGFR</i> mutation testing and <i>EGFR</i> 181946C>T genotyping were performed in 101 advanced lung adenocarcinoma patients using qRT-PCR and PCR-RFLP, respectively. Progression-free survival was defined as the time from the start of TKI therapy to date of progression, and ...[more]

PMID: 35958274

Similar Datasets

Project description:BackgroundA subset of lung adenocarcinoma with EGFR-tyrosine kinase inhibitor sensitizing mutations (mEGFR) is common in non-smokers and women, suggesting that mutational stressors other than smoking are involved.MethodsTargeted sequencing using a custom panel containing 70 cancer-related genes were performed from 73 cases of lung adenocarcinoma with mEGFR (study cohort). In parallel, publicly available data of 47 TCGA-LUAD cases with mEGFR (LUAD cohort) were extracted from the GDC data portal and analyzed by non-negative matrix factorization using the Maftools package.ResultsIn the study cohort, the C > A transversions accounted for 12.9% of all single nucleotide variations (SNVs), comprising the second smallest proportion among SNVs. The E19del-subgroup had a significantly lower mutational burden with significantly higher Ti/Tv ratio than the SNV-subgroup, which includes cases with L858R and other EGFR-TKI sensitizing SNVs. (P = 0.0326 and 0.0002, respectively, Mann-Whitney U test). In the LUAD cohort, the mutational burden was substantially lower than in other TCGA cancer cohorts, and the frequency of C > A transversions was 30.3%, occupying the second frequency. The E19del-subgroup had a lower mutational burden overall and a higher Ti/Tv ratio than the SNV-subgroup (P = 0.0497 and P = 0.0055, respectively, Mann-Whitney U test). Smoking-related signature 4 was observed only in the L858R-subgroup, while ignature 30 and 5 was observed in both groups.ConclusionsLung adenocarcinoma with mEGFR(+) has a lower mutational burden and does not show a characteristic mutation pattern influenced by smoking. E19del and L858R, which are representative subtypes of mEGFR(+) lung adenocarcinoma, differ in terms of mutational spectrum, as the E19del-subgroup has a lower mutation burden and a higher Ti/Tv ratio than the SNV-subgroup. These findings could help explain the differences in the responses to EGFR-TKIs and in the clinical courses between the two lung adenocarcinoma subgroups.

Dataset Information

Evaluation of Clinical and Genetic Determinants of Treatment OutCome In EGFR Mutation Positive Advanced Lung Adenocarcinoma.

Background

Material and methods

Results

Conclusions

Publications

Evaluation of Clinical and Genetic Determinants of Treatment OutCome In EGFR Mutation Positive Advanced Lung Adenocarcinoma.

Similar Datasets

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