Tetraspanin 1 promotes endometriosis leading to ovarian clear cell carcinoma.

Ha‐Yeon Shin,Doo Byung Chay,Joon‐Yong Chung,Eun‐Ju Lee,Wookyeom Yang,Hyun‐Soo Kim,Jae‐Hoon Kim

doi:10.1002/1878-0261.12884

Abstract

Ovarian clear cell carcinoma (OCCC) reportedly develops from endometriosis. However, the molecular mechanism underlying its malignant progression to OCCC remains elusive. This study aimed to identify an essential gene in the malignant transformation of endometriosis to OCCC. We performed RNA sequencing in formalin‐fixed, paraffin‐embedded (FFPE) tissues of endometriosis (n = 9), atypical endometriosis (AtyEm) (n = 18), adjacent endometriosis to OCCC (AdjEm) (n = 7), and OCCC (n = 17). We found that tetraspanin 1 (TSPAN1) mRNA level was significantly increased by 2.4‐ (DESeq2) and 3.4‐fold (edgeR) in AtyEm and by 80.7‐ (DESeq2) and 101‐fold (edgeR) in OCCC relative to endometriosis. We confirmed that TSPAN1 protein level was similarly overexpressed in OCCC tissues and cell lines. In immortalized endometriosis cell lines, TSPAN1 overexpression enhanced cell growth and invasion. Mechanistically, TSPAN1 triggered AMP‐activated protein kinase (AMPK) activity, promoting endometriosis and cell growth. Upregulated levels of TSPAN1 are considered an early event in the development of high‐risk endometriosis that could progress to ovarian cancer. Our study suggests the potential of TSPAN1 as a screening candidate for high‐risk endometriosis.

Highlights

Endometriosis, a benign gynecological disease, occurs in 10% of women of reproductive age
adjacent endometriosis to Ovarian clear cell carcinoma (OCCC) (AdjEm) is histologically endometriosis; it is different from endometriosis and atypical endometriosis (AtyEm) in that it coexists with cancer tissues around it
We included AdjEm in this study as it could explain the progression of OCCC. mRNAs were extracted only from the lesions excised from the FFPE tissues by Laser-capture microdissection (LCM)

Summary

Introduction

Endometriosis, a benign gynecological disease, occurs in 10% of women of reproductive age. Endometrial cells exist outside of the endometrium of the uterus, resulting in chronic pain and infertility [1]. Its cause is unknown, endometriosis is considered to be related to genetics, environment, immunology, angiogenesis, and endocrine disturbance [2].

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