VGLL3 expression is associated with macrophage infiltration and predicts poor prognosis in epithelial ovarian cancer

Razaul Haque; Jaebon Lee; Joon-Yong Chung; Ha-Yeon Shin; Hyosun Kim; Jae-Hoon Kim; Jae Won Yun; Eun-Suk Kang

doi:10.3389/fonc.2023.1152991

VGLL3 expression is associated with macrophage infiltration and predicts poor prognosis in epithelial ovarian cancer

Front Oncol. 2023 Jun 5:13:1152991. doi: 10.3389/fonc.2023.1152991. eCollection 2023.

Authors

Razaul Haque^{1

2}, Jaebon Lee³, Joon-Yong Chung⁴, Ha-Yeon Shin⁵, Hyosun Kim⁵, Jae-Hoon Kim⁵, Jae Won Yun⁶, Eun-Suk Kang^{1

2

7}

Affiliations

¹ Department of Laboratory Medicine and Genetics, Samsung Medical Center, Seoul, Republic of Korea.
² School of Medicine, Sungkyunkwan University, Suwon, Republic of Korea.
³ School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
⁴ Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
⁵ Department of Obstetrics and Gynaecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁶ Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea.
⁷ Cell and Gene Therapy Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea.

Abstract

Background/objective: High-grade serous ovarian carcinoma (HGSOC) is the most common histologic type of epithelial ovarian cancer (EOC). Due to its poor survival outcomes, it is essential to identify novel biomarkers and therapeutic targets. The hippo pathway is crucial in various cancers, including gynaecological cancers. Herein, we examined the expression of the key genes of the hippo pathway and their relationship with clinicopathological significance, immune cells infiltration and the prognosis of HGSOC.

Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data were curated to analyse the mRNA expression as well as the clinicopathological association and correlation with immune cell infiltration in HGSOC. The protein levels of significant genes in the HGSOC tissue were analysed using Tissue Microarray (TMA)-based immunohistochemistry. Finally, DEGs pathway analysis was performed to find the signalling pathways associated with VGLL3.

Results: VGLL3 mRNA expression was significantly correlated with both advanced tumor stage and poor overall survival (OS) (p=0.046 and p=0.003, respectively). The result of IHC analysis also supported the association of VGLL3 protein with poor OS. Further, VGLL3 expression was significantly associated with tumor infiltrating macrophages. VGLL3 expression and macrophages infiltration were both found to be independent prognostic factors (p=0.003 and p=0.024, respectively) for HGSOC. VGLL3 was associated with four known and three novel cancer-related signalling pathways, thus implying that VGLL3 is involved in the deregulation of many genes and pathways.

Conclusion: Our study revealed that VGLL3 may play a distinct role in clinical outcomes and immune cell infiltration in patients with HGSOC and that it could potentially be a prognostic marker of EOC.

Keywords: VGLL3; high-grade serous ovarian carcinoma; hippo pathway; macrophage; prognosis.

Grants and funding

This study was supported by the National Research Foundation of Korea (NRF-2019R1A2C2088715 and 2022R1F1A1075238), which is funded by the Korean government (The Ministry of Science and ICT), South Korea.