Comprehensive analysis and immunohistochemistry localization of NRP1 expression in pancancer and normal individual tissues in relation to SARS‑CoV‑2 susceptibility

Jiewen Fu; Jiayue He; Lianmei Zhang; Jingliang Cheng; Pengfei Zhang; Chunli Wei; Junjiang Fu; Dabing Li

doi:10.3892/etm.2023.12340

Comprehensive analysis and immunohistochemistry localization of NRP1 expression in pancancer and normal individual tissues in relation to SARS‑CoV‑2 susceptibility

Exp Ther Med. 2023 Dec 5;27(2):52. doi: 10.3892/etm.2023.12340. eCollection 2024 Feb.

Authors

Jiewen Fu^{1

2}, Jiayue He¹, Lianmei Zhang^{1

3}, Jingliang Cheng¹, Pengfei Zhang⁴, Chunli Wei¹, Junjiang Fu¹, Dabing Li^{1

2}

Affiliations

¹ Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
² School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
³ Department of Pathology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
⁴ National Health Commission Key Laboratory of Cancer Proteomics, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Abstract

Neuropilin 1 (NRP1/CD304) is a typical membrane-bound co-receptor for vascular endothelial growth factor, semaphorin family members and viral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, NRP1 expression levels across cancer types and the potential role of SARS-CoV-2 infection in patients with cancer are not clear. Online databases, such as The Cancer Genome Atlas database of Human Protein Atlas, Gene Expression Profiling Interactive Analysis and cBioPortal were used for the expression analysis in this study. Immunohistochemical (IHC) staining for NRP1 was performed in the tissues of patients with non-small cell carcinoma. As a result, it was found that NRP1 mRNA and protein expression levels were highest in the female reproductive tissues and the respiratory system, specifically in the nasopharynx, bronchus and fallopian tube, as well as in adipocytes, hepatic stellate cells, Sertoli cells, endothelial cells and dendritic cells. IHC showed that the NRP1 protein was mainly localized to the cytoplasm and membrane in the tissues of patients with non-small cell carcinoma, demonstrating its role in lung infection by SARS-CoV-2, due to invasion of cell membranes by the virus. Levels of NRP1 mRNA were significantly increased in lymphoid neoplasm diffuse large B-cell lymphoma, esophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, kidney renal clear cell carcinoma (KIRC), pancreatic adenocarcinoma, stomach adenocarcinoma and thymoma, and significantly decreased in cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney chromophobe, lung squamous cell carcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma and uterine carcinosarcoma, compared with corresponding healthy tissues in pancancer, indicating roles for viral invasion in most cancer types. Moreover, low NRP1 expression was significantly associated with long overall survival (OS) time in adrenocortical carcinoma, brain lower grade glioma, stomach adenocarcinoma and uveal melanoma, but with short OS time in KIRC only. The ENST00000374867.6 (NRP1-202) isoform is most highly expressed in most cancer types and thus could be involved in tumorigenesis and SARS-CoV-2 invasion in cancer patients. NRP1 may be involved in SARS-CoV-2 invasion in patients with cancer, including those with lung cancer.

Keywords: NRP1/CD304; cancer; coronavirus disease 2019; expression; target.

Grants and funding

Funding: This study was supported by the Foundation of Science and Technology Department of Sichuan Province (grant nos. 2022NSFSC0737, 2023NSFSC0673 and 2022NSFSC1319), in part by the National Natural Science Foundation of China (grant nos. 81672887 and 82073263) and by the Primary Research and Development Plan of Hunan Province (grant no. 2020SK2071).