Ma Qian, Chang Lei, Wang Wenwen, Che Lingyi, Song Xiaoqin, Li Gailing, Zhang Ying, Chen Yibing, Gu Zhuoyu, Ge Xin
Genetics and Prenatal Diagnosis Center, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
Pharmgenomics Pers Med. 2023 Jun 2;16:551-568. doi: 10.2147/PGPM.S400145. eCollection 2023.
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.
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.
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.
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.
有研究表明，卵巢癌（OV）的肿瘤内在异质性和肿瘤微环境（TME）会影响免疫治疗疗效和患者预后。亮氨酰和胱氨酰氨基肽酶（LNPEP）编码一种锌依赖性氨基肽酶，已被证明参与囊泡介导的转运以及I类MHC介导的抗原加工和呈递。然而，LNPEP在OV的TME中的功能及其潜在分子机制尚未明确。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。
在本研究中，利用生物信息学数据库探索LNPEP的表达谱和免疫浸润情况。对LNPEP的生存数据和相互作用分子进行生物信息学分析，以预测LNPEP在OV中的预后价值。通过蛋白质印迹和免疫组织化学验证LNPEP的蛋白水平。
基于TCGA数据，我们的数据显示，与癌旁组织相比，卵巢癌中LNPEP的mRNA表达明显下调，这与蛋白水平相反。重要的是，LNPEP高表达与OV患者的不良预后相关。此外，Cox回归分析表明，LNPEP是OV的独立预后因素。GO和KEGG通路分析表明，LNPEP的共表达基因主要与多种免疫相关通路有关，包括Th1和Th2细胞分化、Th17细胞分化以及免疫调节相互作用。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。
在我们的研究中，我们识别并建立了OV中免疫相关LNPEP的预后特征，这对于预测临床试验的预后具有重要价值，并且可能成为免疫研究的新治疗靶点以及OV潜在的预后生物标志物。
