Leucyl and Cystinyl Aminopeptidase as a Prognostic-Related Biomarker in OV Correlating with Immune Infiltrates

Qian Ma; Lei Chang; Wenwen Wang; Lingyi Che; Xiaoqin Song; Gailing Li; Ying Zhang; Yibing Chen; Zhuoyu Gu; Xin Ge

doi:10.2147/PGPM.S400145

Leucyl and Cystinyl Aminopeptidase as a Prognostic-Related Biomarker in OV Correlating with Immune Infiltrates

Pharmgenomics Pers Med. 2023 Jun 2:16:551-568. doi: 10.2147/PGPM.S400145. eCollection 2023.

Authors

Qian Ma^#¹, Lei Chang^#², Wenwen Wang^#², Lingyi Che¹, Xiaoqin Song³, Gailing Li², Ying Zhang², Yibing Chen¹, Zhuoyu Gu⁴, Xin Ge⁵

Affiliations

¹ Genetics and Prenatal Diagnosis Center, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
² Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
³ Physical Examination Center, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
⁴ Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
⁵ Department of Breast Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

^# Contributed equally.

Abstract

Background: It was indicated that tumor intrinsic heterogeneity and the tumor microenvironment (TME) of ovarian cancer (OV) influence immunotherapy efficacy and patient outcomes. Leucyl and cystinyl aminopeptidase (LNPEP) encodes a zinc-dependent aminopeptidase, which has been proved to participant in the vesicle-mediated transport and class I MHC mediated antigen processing and presentation. However, the function of LNPEP in TME of OV and its potential molecular mechanisms have not been determined. Therefore, we aimed to investigate a prognostic biomarker which may be helpful in identifying TME heterogeneity of ovarian cancer.

Methods: In this study, bioinformatics databases were used to explore the expression profile and immune infiltration of LNPEP. Bioinformatics analyses of survival data and interactors of LNPEP were conducted to predict the prognostic value of LNPEP in OV. The protein levels of LNPEP were validated by Western blot and immunohistochemistry.

Results: Based on the TCGA data, our data displayed that the mRNA expression of LNPEP was markedly down-regulated in ovarian cancer than that in para-cancer tissues, contrary to the protein level. Importantly, high LNPEP expression was associated with poor prognosis in patients with OV. Furthermore, Cox regression analysis showed that LNPEP was an independent prognostic factor in OV. GO and KEGG pathway analyses indicated the co-expressed genes of LNPEP were mainly related to a variety of immune-related pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, and immunoregulatory interaction. Our data also demonstrated that the expression of LNPEP was strongly correlated with immune infiltration levels, immunomodulators, chemokines and chemokine receptors.

Conclusion: In our study, we identified and established a prognostic signature of immune-related LNPEP in OV, which will be of great value in predicting the prognosis of clinical trials and may become a new therapeutic target for immunological research and potential prognostic biomarker in OV.

Keywords: LNPEP; immune infiltration; ovarian cancer; prognosis; tumor microenvironment.

Grants and funding

This work was supported by Henan Provincial Natural Science Foundation (202300410395); The Scientific and Technological Projects of Henan Province (192102310386); The Henan Medical Science and Technology Research Project (SBGJ202103081, SBGJ202102130, SBGJ202102122); Postdoctoral Science Foundation of China (2018M642795, 2018T110743); Young and Middle-aged Health Science and Technology Innovation Talent Project in Henan Province (YXKC2021044); The Leading Talent Cultivation Project of Henan Health Science and Technology Innovation Talents (YXKC2021016); Henan Provincial College and University Research Project (22A320072).