Impact of HFE variants and sex in lung cancer
Autoři:
Sang Y. Lee aff001; Vonn Walter aff002; Junjia Zhu aff002; Anna C. Salzberg aff004; Dajiang J. Liu aff002; James R. Connor aff001
Působiště autorů:
Department of Neurosurgery, The Pennsylvania State University College of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, United States of America
aff001; Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, United States of America
aff002; Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, United States of America
aff003; Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, United States of America
aff004
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0226821
Souhrn
The homeostatic iron regulator protein HFE is involved in regulation of iron acquisition for cells. The prevalence of two common HFE gene variants (H63D, C282Y) has been studied in many cancer types; however, the impact of HFE variants, sex and HFE gene expression in lung cancer has not been studied. We determined the prevalence of HFE variants and their impact on cancer phenotypes in lung cancer cell lines, in lung cancer patient specimens, and using The Cancer Genome Atlas (TCGA) database. We found that seven out of ten human lung cancer cell lines carry the H63D or C282Y HFE variant. Analysis of lung cancer specimens from our institute (Penn State Hershey Medical Center) revealed a sex and genotype interaction risk for metastasis in lung adenocarcinoma (LUAD) patients; H63D HFE is associated with less metastasis in males compared to wild type (WT) HFE; however, females with the H63D HFE variant tend to develop more metastatic tumors than WT female patients. In the TCGA LUAD dataset, the H63D HFE variant was associated with poorer survival in females compared to females with WT HFE. The frequency of C282Y HFE is higher in female lung squamous cell carcinoma (LUSC) patients of TCGA than males, however the C282Y HFE variant did not impact the survival of LUSC patients. In the TCGA LUSC dataset, C282Y HFE patients (especially females) had poorer survival than WT HFE patients. HFE expression level was not affected by HFE genotype status and did not impact patient’s survival, regardless of sex. In summary, these data suggest that there is a sexually dimorphic effect of HFE polymorphisms in the survival and metastatic disease in lung cancer.
Klíčová slova:
Gene expression – Lung and intrathoracic tumors – Metastasis – Adenocarcinomas – Adenocarcinoma of the lung – Variant genotypes – Non-small cell lung cancer – Squamous cell lung carcinoma
Zdroje
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