Significance of intratissue estrogen concentration coupled with estrogen receptors levels in colorectal cancer prognosis
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Agnieszka Anna Rawłuszko-Wieczorek1, Łukasz Marczak2, Nikodem Horst3,*, Karolina Horbacka3,*, Piotr Krokowicz3 and Paweł Piotr Jagodziński1
1Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznan, Poland
2European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
3Department of General and Colorectal Surgery, Poznań University of Medical Sciences, Poznan, Poland
*These authors have contributed equally to this work
Agnieszka Anna Rawłuszko-Wieczorek, email: [email protected]
Keywords: estrogen; estrogen receptors; colorectal cancer
Received: April 28, 2017 Accepted: December 05, 2017 Published: December 14, 2017
Dysregulation of estrogen related pathways is implicated colorectal cancer (CRC) development. However, significance of intratissue concentration of estrone (E1) and 17β-estradiol (E2) in relation to estrogen receptor (ESR) expression level was not addressed so far. Herein, we measured E1 and E2 intratissue concentration using liquid chromatography electrospray ionization tandem mass spectrometry (ESI LC/MS) and mRNA levels of ESR1 and ESR2 using RT-qPCR in cancerous and histopathologically unchanged tissue from 75 and 110 CRC patients, respectively. The obtained results were associated with clinicopathological factors, expression of estrogen dependent genes (CTNNB1, CCND1) and prognostic significance. We found no statistically significant differences in E1 or E2 concentration between cancerous tissue and histopathologically unchanged counterparts. Moreover, mRNA levels of ESR1 and ESR2 were significantly decreased in cancerous tissue compared with histopathologically unchanged (p=0.00001). Log rank analysis revealed no benefit of low E1 to E2 ratio, high E1, E2 concentration or ESR1, ESR2 mRNA level for patients’ overall (OS) and disease free survival (DFS). Interestingly, we have observed that patients with low ESR1 mRNA level coupled with low E1 intratissue concentration had a significant decrease in DFS compared with group of patients with high ESR1 mRNA level and high E1 concentration (HR=0.16, 95% CI 0.02-1.05; p=0.06). Furthermore, patients with low E1 concentration and low ESR1 transcript had significantly higher CTNNB1 and CCND1 mRNA level compare with subgroup with high level of both grouping factors. Our study indicates a potential value of estrogen intratissue concentration and its receptor expression level for CRC patients’ prognosis.
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