LAMC1 is a Prognostic Factor and a Potential Therapeutic Target in Endometrial Cancer

Overview

Journal J Gynecol Oncol

Specialties Gynecology & Obstetrics
Oncology

Date 2020 Jan 9

PMID 31912669

Citations 34

Authors

Haruko Kunitomi

Yusuke Kobayashi

Ren Chin Wu

Takashi Takeda

Eiichiro Tominaga

Kouji Banno

Daisuke Aoki

Affiliations

Soon will be listed here.

Abstract

Objective: With the emerging significance of genetic profiles in the management of endometrial cancer, the identification of tumor-driving genes with prognostic value is a pressing need. The gene, encoding the laminin subunit gamma 1 (LAMC1) protein, has been reported to be involved in the progression of various malignant tumors. In this study, we aimed to investigate the role of LAMC1 in endometrial cancer and elucidate the underlying mechanism.

Methods: We evaluated the immunohistochemical expression of LAMC1 in atypical endometrial hyperplasia and endometrial cancer. Within the endometrial cancer cases, we analyzed the association of LAMC1 overexpression with clinicopathological factors and prognosis. Furthermore, to indentify genes influenced by LAMC1 overexpression, we transfected HEC50B and SPAC-S cells with siRNA targeting and conducted microarray gene expression assays.

Results: While none of the atypical endometrial hyperplasia specimens exhibited LAMC1 overexpression, endometrial cancer possessed a significantly higher LAMC1 overexpression rate. LAMC1 overexpression was strongly associated with histological type, lymphovascular space invasion, lymph node metastasis, advanced International Federation of Gynecology and Obstetrics stage, and poor overall survival in endometrial cancer. Gene expression microarray analysis identified 8 genes correlated with tumor progression (, , , , , , , and ) that were commonly influenced in HEC50B and SPAC-S by silencing.

Conclusion: LAMC1 overexpression is a potent biomarker for identifying endometrial cancer patients needing aggressive adjuvant therapy. We elucidated 8 candidate genes that may mediate progression of LAMC1 overexpressing cancer. Further investigation of the underlying mechanism should lead to the discovery of new therapeutic targets.

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