Nomogram based on preoperative CT imaging predicts the EGFR mutation status in lung adenocarcinoma.
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ABSTRACT:
SUBMITTER: Zhang G
PROVIDER: S-EPMC7691609 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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Nomogram based on preoperative CT imaging predicts the EGFR mutation status in lung adenocarcinoma.
Zhang Guojin G Zhang Jing J Cao Yuntai Y Zhao Zhiyong Z Li Shenglin S Deng Liangna L Zhou Junlin J
Translational oncology 20201121 1
Tyrosine kinase inhibitors (TKIs) provide clinical benefits to the lung cancer patients with epidermal growth factor receptor (EGFR) mutations. However, non-invasively determine EGFR mutation status in patients before targeted therapy remains a challenge. This study aimed to develop and validate a nomogram for preoperative prediction of EGFR mutation status in patients with lung adenocarcinoma. The medical records of 403 patients with lung adenocarcinoma confirmed by histology from January 2016 ...[more]
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Project description:IntroductionIn lung adenocarcinoma, the mutational spectrum is dominated by EGFR and KRAS mutations. Improved knowledge about genomic and transcriptional alterations in and between mutation-defined subgroups may identify genes involved in disease development or progression.MethodsGenomic profiles from 457 adenocarcinomas, including 113 EGFR-mutated, 134 KRAS-mutated and 210 EGFR and KRAS-wild type tumors (EGFRwt/KRASwt), and gene expression profiles from 914 adenocarcinomas, including 309 EGFR-mutated, 192 KRAS-mutated, and 413 EGFRwt/KRASwt tumors, were assembled from different repositories. Genomic and transcriptional differences between the three mutational groups were analyzed by both supervised and unsupervised methods.ResultsEGFR-mutated adenocarcinomas displayed a larger number of copy number alterations and recurrent amplifications, a higher fraction of total loss-of-heterozygosity, higher genomic complexity, and a more distinct expression pattern than EGFR-wild type adenocarcinomas. Several of these differences were also consistent when the three mutational groups were stratified by stage, gender and smoking status. Specific copy number alterations were associated with mutation status, predominantly including regions of gain with the highest frequency in EGFR-mutated tumors. Differential regions included both large and small regions of gain on 1p, 5q34-q35.3, 7p, 7q11.21, 12p12.1, 16p, and 21q, and losses on 6q16.3-q21, 8p, and 9p, with 20-40% frequency differences between the mutational groups. Supervised gene expression analyses identified 96 consistently differentially expressed genes between the mutational groups, and together with unsupervised analyses these analyses highlighted the difficulty in broadly resolving the three mutational groups into distinct transcriptional entities.ConclusionsWe provide a comprehensive overview of the genomic and transcriptional landscape in lung adenocarcinoma stratified by EGFR and KRAS mutations. Our analyses suggest that the overall genomic and transcriptional landscape of lung adenocarcinoma is affected, but only to a minor extent, by EGFR and KRAS mutation status.
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