Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL

Xujuan Zhang; Pengxiang Zhao; Mingshen Ma; Hao Wu; Rui Liu; Ziyi Liu; Zisong Cai; Mengyu Liu; Fei Xie; Xuemei Ma

doi:10.3389/fmed.2023.1168977

Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL

Front Med (Lausanne). 2023 Jun 29:10:1168977. doi: 10.3389/fmed.2023.1168977. eCollection 2023.

Authors

Xujuan Zhang^#^{1

2

3}, Pengxiang Zhao^#^{1

2

3}, Mingshen Ma^#⁴, Hao Wu^{1

2

3}, Rui Liu⁵, Ziyi Liu^{1

2

3}, Zisong Cai^{1

2

3}, Mengyu Liu^{1

2

3}, Fei Xie^{1

2

3}, Xuemei Ma^{1

2

3}

Affiliations

¹ Faculty of Environment and Life, Beijing University of Technology, Beijing, China.
² Beijing Molecular Hydrogen Research Center, Beijing, China.
³ Beijing International Science and Technology Cooperation Base of Antivirus Drug, Beijing, China.
⁴ Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
⁵ Beijing Tongren Hospital, Capital Medical University, Beijing, China.

^# Contributed equally.

Abstract

Purpose: Lacrimal gland benign lymphoepithelial lesion (LGBLEL) is an IgG4-related disease of unknown etiology with a risk for malignant transformation. Estrogen is considered to be related to LGBLEL onset.

Methods: Seventy-eight LGBLEL and 13 control clinical samples were collected and studied to determine the relationship between estrogen and its receptors and LGBLEL development.

Results: The serological analysis revealed no significant differences in the levels of three estrogens be-tween the LGBLEL and control groups. However, immunohistochemical analyses indicated that the expression levels of ERβ and its downstream receptor RERG were relatively lower in LGBLEL samples than in control samples, with higher expression in the lacrimal gland and lower expression in the lymphocyte infiltration region. However, low expression of ERα was detected. The transcriptome sequence analysis revealed upregulated genes associated with LGBLEL enriched in lymphocyte proliferation and activation function; downregulated genes were enriched in epithelial and vascular proliferation functions. The key genes and gene networks were further analyzed. Interactions between B cells and epithelial cells were analyzed due to the identified involvement of leukocyte subsets and epithelial cells. B cell proliferation was found to potentially contribute to lacrimal gland apoptosis.

Conclusion: Therefore, the tissue-heterogeneous expression pattern of ERβ is potentially related to the clinical manifestations and progression of LGBLEL, although further investigations are required to confirm this finding.

Keywords: B lymphocyte proliferation; ERβ; LGBLEL; clinical manifestations; lacrimal gland apoptosis; tumor development.

Grants and funding

This research was funded by the Natural Science Foundation of Beijing (7222025), the Beijing Hospitals Authority’ Ascent Plan (DFL20190201), and the Beijing New-star Plan of Science and Technology (20220484218).