4.6 Article

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

Journal

FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.636365

Keywords

estrogen receptor; progesterone receptor; expression profile; pathological correlation; genetic alteration; clinical relevance; immunological correlation; survival contribution

Categories

Funding

  1. National Natural Science Foundation of China [31970696, 81502975, 81972472]
  2. China Postdoctoral Science Foundation [2016T90413, 2015M581693]
  3. Natural Science Foundation of Anhui [2008085MH276]

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ERα, ERβ, and PGR proteins were found to be differentially expressed in ovarian and uterine cancers, correlating with tumor stage and grade. In addition, the mRNA expression levels of ESR1, ESR2, and PGR were significantly associated with immunomodulators and immune cells. This suggests that ESR1, ESR2, and PGR could serve as potential prognostic markers and therapeutic targets for various cancers.
Introduction 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 via pan-cancer analysis. Methods The pan-cancer mRNA expression levels, genetic variations, and prognostic values of ESR1, ESR2, and PGR 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). Results ESR1, ESR2, and PGR 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 via 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 ESR1, ESR2, and PGR mRNAs were significantly associated with the expression of immunomodulators and immune cells. Conclusion ESR1, ESR2, and PGR are potential prognostic markers and therapeutic targets, as well as important factors for the prediction, evaluation, and individualized treatment in several cancer types.

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