The ferroxidase HEPHaestin in Lung cancer: Pathological Significance and Prognostic Value

Iron is a fundamental nutrient utilized by living cells to support several key cellular processes. Despite its paramount role to sustain cell survival, excess of labile iron availability can inflict severe cell damage via reactive oxygen species generation which, in turn, can promote neoplastic transformation. The lung is particularly sensitive to iron-induced oxidative stress, given the high oxygen tensions herein present. Moreover, cigarette smoke as well as air pollution particulate can function as vehicles of iron supply, leading to an iron dysregulation condition shown to be crucial in the pathogenesis of several respiratory diseases including lung cancer. Hephaestin (HEPH) belongs to a group of exocytoplasmic ferroxidases emerged to contribute to cellular iron homeostasis by favouring its export. Although HEPH can affect the concentration of intracellular iron labile pool, its expression in lung cancer and its influence on prognosis have not been investigated. In this study we explored the expression pattern and prognostic value of HEPH in the most prevalent histotypes of lung cancers including lung adenocarcinoma and lung squamous cell carcinoma across in silico analyses using UALCAN, Gepia and Kaplan-Meier plotter bioninformatics. We took advantage of TIMER to assess the correlation between HEPH and tumour infiltrating immune and non-immune cells. Then we performed immunohistochemical analysis to dissect the presence of HEPH either in "healthy" and tumor lung tissues. Overall, our data suggest a positive correlation between higher level of HEPH expression with a favorable prognosis in both cancer histotypes.