AUTHOR=Shen Yu-ting , Huang Xing , Zhang Gang , Jiang Bo , Li Cheng-jun , Wu Zheng-sheng 

TITLE=Pan-Cancer Prognostic Role and Targeting Potential of the Estrogen-Progesterone Axis

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.636365

DOI=10.3389/fonc.2021.636365

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>Estrogen receptors (ESRs) and progesterone receptors (PGRs) are associated with the development and progression of various tumors. The feasibility of ESRs and PGRs as prognostic markers and therapeutic targets for multiple cancers was evaluated <italic>via</italic> pan-cancer analysis.</p></sec><sec><title>Methods</title><p>The pan-cancer mRNA expression levels, genetic variations, and prognostic values of <italic>ESR1</italic>, <italic>ESR2</italic>, and <italic>PGR</italic> were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and cBioPortal. The expression levels of ERa, ERb, and PGR proteins were detected by immunohistochemical staining using paraffin-embedded tissue specimens of ovarian serous cystadenocarcinoma (OV) and uterine endometrioid adenocarcinoma (UTEA). Correlation between immunomodulators and immune cells was determined based on the Tumor and Immune System Interaction Database (TISIDB).</p></sec><sec><title>Results</title><p><italic>ESR1</italic>, <italic>ESR2</italic>, and <italic>PGR</italic> mRNAs were found to be differentially expressed in different cancer types, and were associated with tumor progression and clinical prognosis. ERa, ERb, and PGR proteins were further determined to be significantly differentially expressed in OV and UTEA <italic>via</italic> immunohistochemical staining. The expression of ERa protein was positively correlated with a high tumor stage, whereas the expression of PGR protein was conversely associated with a high tumor stage in patients with OV. In patients with UTEA, the expression levels of both ERa and PGR proteins were conversely associated with tumor grade and stage. In addition, the expression levels of <italic>ESR1</italic>, <italic>ESR2</italic>, and <italic>PGR</italic> mRNAs were significantly associated with the expression of immunomodulators and immune cells.</p></sec><sec><title>Conclusion</title><p><italic>ESR1</italic>, <italic>ESR2</italic>, and <italic>PGR</italic> are potential prognostic markers and therapeutic targets, as well as important factors for the prediction, evaluation, and individualized treatment in several cancer types.</p></sec>