Neuropilin1 Expression Acts as a Prognostic Marker in Stomach Adenocarcinoma by Predicting the Infiltration of Treg Cells and M2 Macrophages.

Kyung Eun Kim,Ji Young Kang,Minchan Gil

doi:10.3390/jcm9051430

Kyung Eun Kim, Ji Young Kang + Show 1 more

Open Access

https://doi.org/10.3390/jcm9051430

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Abstract

Neuropilin1 (NRP1) plays a critical role in tumor progression and immune responses. Although the roles of NRP1 in various tumors have been investigated, the clinical relevance of NRP1 expression in stomach adenocarcinoma (STAD) has not been studied. To investigate the use of NRP1 as a prognostic biomarker of STAD, we analyzed NRP1 mRNA expression and its correlation with patient survival and immune cell infiltration using various databases. NRP1 mRNA expression was significantly higher in STAD than normal tissues, and Kaplan-Meier survival analysis showed that NRP1 expression was significantly associated with poor prognosis in patients with STAD. To elucidate the related mechanism, we analyzed the correlation between NRP1 expression and immune cell infiltration level. In particular, the infiltration of immune-suppressive cells, such as regulatory T (Treg) cells and M2 macrophage, was significantly increased by NRP1 expression. In addition, the expression of interleukin (IL)-35, IL-10, and TGF-β1 was also positively correlated with NRP1 expression, resulting in the immune suppression. Collectively in this study, our integrated analysis using various clinical databases shows that the significant correlation between NRP1 expression and the infiltration of Treg cells and M2 macrophage explains poor prognosis mechanism in STAD, suggesting the clinical relevance of NRP1 expression as a prognostic biomarker for STAD patients.

Highlights

Stomach adenocarcinoma (STAD) is one of the most common malignancies and is third in cancer-related deaths worldwide [1]
The association between mRNA levels and promoter methylation of NRP1 and clinicopathological features was analyzed to determine the prognostic value of NRP1 in patients with stomach adenocarcinoma (STAD). mRNA levels and promoter methylation of NRP1 were separately analyzed with STAD patient characteristics, including individual cancer stage, age, histological subtype, race, gender, and tumor grade, compared to the normal tissues
We assessed cancer prognosis, including overall survival (OS), first progression (FS), and post progression survival (PPS) using gene chip datasets of Kaplan-Meier survival plotter with best cut off option, which split patient groups at the NRP1 expression level to minimize log rank P-value [36]

Summary

Introduction

Stomach adenocarcinoma (STAD) is one of the most common malignancies and is third in cancer-related deaths worldwide [1]. High levels of Treg cells have been observed in patients with various tumors These are associated with poor prognosis of various types of tumor including gastric cancer, breast cancer and ovarian cancer [19,21,22,23]. These studies provide strong evidences that M2 macrophages and Treg cells are highly correlated with tumor immunity and patient prognosis. Our study suggests that NRP1 expression could act as an effective prognostic marker by predicting the infiltration of Treg cells and M2 macrophages, indicating the role of NRP1 as a prognosis biomarker in patients with STAD

Analysis of NRP1 Expression in Various Types of Tumors and Normal Tissues

Results

Association between NRP1 Expression and Prognosis in Patients with STAD

Conclusions