J Cancer 2021; 12(12):3648-3659. doi:10.7150/jca.52851

Research Paper

Neuropilin-1 predicts poor prognosis and promotes tumor metastasis through epithelial-mesenchymal transition in gastric cancer

Qianna Jin1,5, Qianqian Ren1,5, Xiaona Chang3, Haixing Yu2, Xin Jin2, Xiaoming Lu2, Nan He2✉, Guobin Wang4

1. Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
2. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
3. Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
4. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
5. Hubei Province Key Laboratory of Molecular Imaging

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Citation:
Jin Q, Ren Q, Chang X, Yu H, Jin X, Lu X, He N, Wang G. Neuropilin-1 predicts poor prognosis and promotes tumor metastasis through epithelial-mesenchymal transition in gastric cancer. J Cancer 2021; 12(12):3648-3659. doi:10.7150/jca.52851. Available from https://www.jcancer.org/v12p3648.htm

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Abstract

We aimed to determine whether Neuropilin-1 (NRP1) promotes gastric cancer (GC) metastasis by inducing epithelial-mesenchymal transition (EMT), and to clarify its regulatory mechanism. Using the data of GC patients in The Cancer Genome Atlas (TCGA) and Gene Tissue Expression (GTEx) databases, combined with the data of GC patients in our medical center, the effect of NRP1 on the prognosis of GC patients were analyzed. Then, we investigated the role of NRP1 in GC metastasis and its potential mechanism. The level of NRP1 was up-regulated in GC tissues and associated with poor prognosis of GC patients. The expression of NRP1 was closely related to maximum tumor diameter, invasion depth, lymphnode metastasis, distant metastasis, and advanced TNM stage, and was an independent prognostic factor for overall survival (OS) in GC patients. Besides, the results of in vitro indicated that NRP1 could induce EMT to promote the migration and invasion of GC cells by activating PI3K/Akt signaling pathway, and the HGF/c-Met axis was involved in this process. This study determined that NRP1 was a gene that promotes gastric cancer. NRP1 induced EMT to enhance the migration and invasion ability of GC cells by activating PI3K/Akt signaling pathway. NRP1 was an independent prognostic marker for OS in GC patients and expected to be a therapeutic target for GC patients.

Keywords: NRP1, Stomach neoplasms, Prognosis, EMT, Oncogenes