Abstract
Neuronal regeneration related protein (NREP), also known as P311, has been reported to participate in multiple biological processes. The detection of tumor biomarker favored a non-invasive early entry for cancer diagnosis and disease monitoring to prevent its worsening symptoms. This study is intended to investigate the clinical roles of NREP in gastric cancer (GC) and its effect on gastric cancer cell proliferation and angiogenesis. Our results demonstrated that NREP was typically upregulated in GC tissues compared with normal control. The Kaplan–Meier analysis showed correlations between increased NREP level and poor survival, indicating the prognostic value of NREP in GC patients. The expression levels of NREP varied by races, clinical T stages, and histologic grades. NREP expression was associated with tumor-associated immune infiltration. The NREP expression was powerfully associated with clinical characteristics of GC patients, in particular, with T stage and histologic grade. Gene ontology and KEGG signaling analysis indicated that NREP-related genes were predominantly enriched in various pathways. Additionally, knockdown of NREP inhibited human gastric adenocarcinoma cell proliferation and angiogenesis. Collectively, our results suggested that NREP may be an excellent biomarker for the clinical diagnosis, prognosis, and therapy of GC.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We would like to thank the Affiliated Cancer Hospital of Zhengzhou University and all the authors for their help.
Funding
This work was supported by the Henan Province Medical Science and Technology Tackling Program, the Foundation for 2020 Henan Province Medical Science and Technology Tackling Program (Grant No. LHGJ20200160).
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QL and JW: designed the study. QL and LF: performed the experiments. DW: analyzed the data. QL: The first draft of the manuscript was written. All authors have read and approved the final manuscript.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of The Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital.
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10528_2022_10276_MOESM1_ESM.tif
Supplementary file1 (TIF 410 KB) Supplementary fig. 1 The results of transfection efficient in SGC-7901 and AGS cells. Western blotting was performed to validate the transfection efficient in SGC-7901 and AGS cells. NREP protein level was reduced after transfection of si-NREP. ***P <0.001.
10528_2022_10276_MOESM2_ESM.tif
Supplementary file2 (TIF 674 KB) Supplementary fig. 2 NREP overexpression promotes human gastric adenocarcinoma cell proliferation. (A and B) Cell viability was detected by CCK-8 assays after NREP overexpression vector transfection in SGC-7901 (A) and AGS (B) cells. Representative images and quantitative analysis of EdU-positive cells in SGC-7901 (C) and AGS (D) cells at 48 h post transfection were shown. *P <0.05, **P <0.01, ***P <0.001
10528_2022_10276_MOESM3_ESM.tif
Supplementary file3 (TIF 732 KB) Supplementary fig. 3 NREP overexpression promotes angiogenesis. HUVECs were treated with the culture supernatant from SGC-7901 (A) or AGS (B) cells with NREP overexpression. Representative images of angiogenesis and quantitative analysis of angiogenic tubes in HUVECs were shown. *P <0.05
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Li, Q., Fu, L., Wu, D. et al. NREP is a Diagnostic and Prognostic Biomarker, and Promotes Gastric Cancer Cell Proliferation and Angiogenesis. Biochem Genet 61, 669–686 (2023). https://doi.org/10.1007/s10528-022-10276-7
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DOI: https://doi.org/10.1007/s10528-022-10276-7