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NRSN2 是胃癌的预后生物标志物,并促进胃癌细胞的生长和迁移。

NRSN2 is a Prognostic Biomarker in Gastric Cancer and Facilitates the Growth and Migration of Gastric Cancer Cells.

机构信息

Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, Hubei, China.

Department of Coloproctological Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, Hubei, China.

出版信息

Protein Pept Lett. 2023;30(5):427-438. doi: 10.2174/0929866530666230314160234.

Abstract

BACKGROUND

Neurensin-2 (NRSN2) is reported to be associated with the progression of many tumors. This work aimed at investigating the biological function and prognostic significance of NRSN2 in gastric cancer (GC).

METHODS

NRSN2 expression in various cancer tissue was analyzed by the TIMER database. NRSN2 expression in GC tissue samples of different groups was analyzed by the UALCAN database. The survival analysis was performed with the Kaplan-Meier database. NRSN2 expression in GC tissues and cell lines was measured by qRT-PCR and Western blot. CCK-8, Transwell and scratch healing assays were conducted to detect the proliferative, migrative and invasive capabilities of GC cells, respectively. The LinkedOmics database and StarBase database were utilized to analyze the related genes with NRSN2 in GC. The association of NRSN2 expression with tumor immune infiltrating cells and molecular markers of immune cells was investigated with the TIMER database.

RESULTS

NRSN2 expression was up-regulated in GC tissues, which was correlated with GC tumor grade, lymph node metastasis, and TP53 mutation. The prognosis of GC patients with high NRSN2 expression was worse than those of the patients with low NRSN2 expression. NRSN2 expression was also associated with the TNM stage, and Lauren subtype of GC patients. NRSN2 overexpression promoted the growth, migration and invasion of GC cells lines; knocking down NRSN2 worked oppositely. NRSN2 expression in GC was associated with Wnt, p53, and NOD-like receptor signaling pathways. NRSN2 expression was also significantly associated with the infiltration of CD8 T cells, CD4 T cells, macrophages, neutrophils, and dendritic cells in the GC microenvironment.

CONCLUSION

NRSN2 expression in GC tissues is up-regulated, which correlates with a poor prognosis and immune cell infiltration of GC patients. NRSN2 facilitates the growth and aggressiveness of GC cells, implying that it may be a diagnostic biomarker and therapy target for GC.

摘要

背景

神经调节素-2(NRSN2)被报道与许多肿瘤的进展有关。本研究旨在探讨 NRSN2 在胃癌(GC)中的生物学功能和预后意义。

方法

通过 TIMER 数据库分析各种癌症组织中 NRSN2 的表达。通过 UALCAN 数据库分析不同组别 GC 组织样本中 NRSN2 的表达。通过 Kaplan-Meier 数据库进行生存分析。通过 qRT-PCR 和 Western blot 检测 GC 组织和细胞系中 NRSN2 的表达。通过 CCK-8、Transwell 和划痕愈合实验分别检测 GC 细胞的增殖、迁移和侵袭能力。利用 LinkedOmics 数据库和 StarBase 数据库分析 GC 中与 NRSN2 相关的基因。通过 TIMER 数据库分析 NRSN2 表达与肿瘤免疫浸润细胞和免疫细胞分子标志物的关系。

结果

NRSN2 在 GC 组织中表达上调,与 GC 肿瘤分级、淋巴结转移和 TP53 突变相关。高 NRSN2 表达的 GC 患者预后较低 NRSN2 表达的患者差。NRSN2 表达还与 GC 患者的 TNM 分期和 Lauren 亚型相关。NRSN2 过表达促进 GC 细胞系的生长、迁移和侵袭;敲低 NRSN2 则起到相反的作用。GC 中 NRSN2 的表达与 Wnt、p53 和 NOD 样受体信号通路相关。NRSN2 表达与 GC 微环境中 CD8 T 细胞、CD4 T 细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润也有显著相关性。

结论

GC 组织中 NRSN2 的表达上调,与 GC 患者的预后不良和免疫细胞浸润相关。NRSN2 促进 GC 细胞的生长和侵袭能力,提示其可能成为 GC 的诊断标志物和治疗靶点。

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