Abstract
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.
Highlights
Lung cancer is the second most common cancer in both men and women and is the leading cause of cancer deaths in the US [1]
Hershey Medical Center (PSHMC) glioblastoma (GBM) patient’s samples, we demonstrated poorer overall survival in male GBM patients with H63D HFE than male wild type (WT) HFE GBM patients [39] this finding was not observed in The Cancer Genome Atlas (TCGA) GBM samples [40]
Human lung cancer cell lines were maintained in Roswell Park Memorial Institute (RPMI) media 1640 with 1X Penicillin-Streptomycin and 10% fetal bovine serum (FBS)
Summary
Lung cancer is the second most common cancer in both men and women and is the leading cause of cancer deaths in the US [1]. There are two types of lung cancers: non-small cell lung. HFE genotype and expression in lung cancer not necessarily represent the official views of the Pennsylvania Department of Health and National Institutes of Health. There was no additional external funding received for this study
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