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

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S400145

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

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引用次数: 0

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.

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亮氨酸和胱氨酸氨基肽酶作为OV与免疫浸润相关的预后相关生物标志物。

背景:卵巢癌(OV)的肿瘤内在异质性和肿瘤微环境(TME)影响免疫治疗的疗效和患者预后。亮氨酸和胱氨酸氨基肽酶(LNPEP)编码锌依赖的氨基肽酶，该酶已被证明参与囊泡介导的转运和I类MHC介导的抗原加工和递呈。然而，LNPEP在OV TME中的作用及其潜在的分子机制尚未确定。因此，我们旨在研究一种可能有助于识别卵巢癌TME异质性的预后生物标志物。方法:利用生物信息学数据库对LNPEP的表达谱和免疫浸润进行研究。对LNPEP的生存数据和相互作用物进行生物信息学分析，以预测LNPEP在OV中的预后价值。Western blot和免疫组化检测LNPEP蛋白水平。结果:基于TCGA数据，我们的数据显示LNPEP mRNA在卵巢癌中的表达明显低于癌旁组织，与蛋白水平相反。重要的是，高LNPEP表达与OV患者的不良预后相关。此外，Cox回归分析显示LNPEP是OV的独立预后因素。GO和KEGG通路分析表明，LNPEP共表达基因主要与多种免疫相关通路相关，包括Th1和Th2细胞分化、Th17细胞分化、免疫调节相互作用等。我们的数据还表明，LNPEP的表达与免疫浸润水平、免疫调节剂、趋化因子和趋化因子受体密切相关。结论:本研究鉴定并建立了OV中免疫相关LNPEP的预后标志，对临床试验的预后预测具有重要价值，可能成为OV免疫学研究的新的治疗靶点和潜在的预后生物标志物。

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来源期刊

Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

3.30

自引率

5.30%

发文量

110

审稿时长

16 weeks

期刊介绍： Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.