Abstract
The biological roles of estrogen receptor 1 (ERS1), estrogen receptor 2 (ERS2), and aromatase (CYP19A1) genes in the development of non-small cell lung cancer (NSCLC) is unclear, as is the use of their expression as a prognostic factor. The aim of this study was to investigate the prognostic value of estrogen receptors and aromatase mRNA expression, along with aromatase protein concentration, in resected NSCLC patients. Tumor and non-tumor lung tissue samples were analyzed for the mRNA expression of ERS1, ERS2 and CYP19A1 by RT-PCR. Aromatase concentration was measured with an ELISA. A total of 96 patients were included. ERS1 expression was significantly higher in non-tumor tissue than in tumor samples. Two gene expression categories were created for each gene (and protein): high and low. ERS1 high category showed increased overall survival (OS) when compared to the low expression category. Aromatase protein concentration was significantly higher in tumor samples. Higher ERS1 expression in tumor tissues was related to longer overall survival. The analysis of gene expression combinations provides evidence for longer OS when both ERS1 and ERS2 are highly expressed. ESR1, alone or in combination with ERS2 or CYP19A1, is the most determining prognostic factor within the analyzed 3 genes. It seems that ERS1 can play a role in NSCLC prognosis, alone or in combination with other genes such as ERS2 or Cyp19a1. ERS2 in combination with aromatase concentration could have a similar function.
Highlights
Taking statistics from the USA as an example of the evolution of lung cancer in developed countries, it is clear that the prevention and cure of this particular type of cancer needs to improve
Estrogens induce cell proliferation through the activation of certain growth factor genes such as epidermal growth factor and insulin-like growth factor, mediators of mitogenesis in lung tumors [9]. They exert their function through two different specific estrogen receptors, estrogen receptor-a (ERa) and estrogen receptor-b (ERb), members of the nuclear receptor superfamily of transcription factors [10], and through two different pathways, genomic and non-genomic, with the same biological effects: proliferation, growth, apoptosis, differentiation and angiogenesis
The strongest association was found for ERS1 combined with CYP19A1 gene expression: the highest overall survival (OS) rates were found for categories HighERS1+Low-CYP19A1 and High-ERS1+High CYP19A1, while that for category Low-ERS1-high-CYP19A1 was considerably lower
Summary
Taking statistics from the USA as an example of the evolution of lung cancer in developed countries, it is clear that the prevention and cure of this particular type of cancer needs to improve. Estrogens induce cell proliferation through the activation of certain growth factor genes such as epidermal growth factor and insulin-like growth factor, mediators of mitogenesis in lung tumors [9]. They exert their function through two different specific estrogen receptors, estrogen receptor-a (ERa) and estrogen receptor-b (ERb), members of the nuclear receptor superfamily of transcription factors [10], and through two different pathways, genomic and non-genomic, with the same biological effects: proliferation, growth, apoptosis, differentiation and angiogenesis. There is a feedback loop, because estrogens induce the activation of epidermal growth factor that leads to an
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