Prognostic Significance of High NPC2 Expression in Gastric Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2023 Nov 24

PMID 38001127

Authors

Yunzhuang Yao

Jinnan Ren

Junhui Lu

Yue Sui

Jingwen Gong

Xing Chen

Affiliations

Soon will be listed here.

Abstract

Gastric cancer is one of the most common malignancies worldwide, and the third leading cause of cancer-related death. The identification of novel biomarkers and therapeutic targets is critical to improve the prognosis. A total of 380 patients with primary gastric cancer from the TCGA database were analyzed. The receiver operating characteristic curves were plotted. We further evaluated the independent prognostic ability of NPC2 expression for overall survival (OS) and relapse-free survival (RFS) through the Kaplan-Meier curve and Cox analysis. The NPC2 expression was significantly higher (P < 0.001) in gastric cancer. High NPC2 expression was significantly (P < 0.0001) associated with poor OS and poor RFS. The age, stage, radiation therapy, residual tumor, and NPC2 expression showed independent prognostic value for OS. The gender and NPC2 expression showed independent prognostic value for RFS. The higher NPC2 expression was observed in gastric cancer, compared with adjacent normal tissue (P < 0.001), confirmed by the IHC staining. The CCK-8 assay showed that NPC2 knockdown inhibits cell proliferation while NPC2 overexpression promotes cell proliferation (P < 0.05). NPC2 expression may serve as a promising prognostic biomarker for patients with gastric cancer.

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References

Chi Y, Wang H, Wang F, Ding M . PHTF2 regulates lipids metabolism in gastric cancer. Aging (Albany NY). 2020; 12(8):6600-6610. PMC: 7202541. DOI: 10.18632/aging.102995. View

Liao Y, Lin M, Yen C, Lin Y, Wang C, Huang S . Characterization of Niemann-Pick Type C2 protein expression in multiple cancers using a novel NPC2 monoclonal antibody. PLoS One. 2013; 8(10):e77586. PMC: 3798307. DOI: 10.1371/journal.pone.0077586. View

Ajani J, DAmico T, Bentrem D, Chao J, Cooke D, Corvera C . Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022; 20(2):167-192. DOI: 10.6004/jnccn.2022.0008. View

de Mello R, Amaral G, Neves N, Lippo E, Parini F, Xu S . Current and potential biomarkers in gastric cancer: a critical review of the literature. Future Oncol. 2021; 17(25):3383-3396. DOI: 10.2217/fon-2021-0084. View

Adachi T, Matsumoto Y, Inagaki Y, Sekimizu K . Niemann-Pick disease type C2 protein induces autophagy and inhibits growth in FM3A breast cancer cells. Drug Discov Ther. 2015; 9(4):282-8. DOI: 10.5582/ddt.2015.01014. View

Xie J, Huang X, Chen Q, Ma Y, Zhao Y, Liu L . mA modification-mediated BATF2 acts as a tumor suppressor in gastric cancer through inhibition of ERK signaling. Mol Cancer. 2020; 19(1):114. PMC: 7350710. DOI: 10.1186/s12943-020-01223-4. View

Cai H, Jiao Y, Li Y, Yang Z, He M, Liu Y . Low CYP24A1 mRNA expression and its role in prognosis of breast cancer. Sci Rep. 2019; 9(1):13714. PMC: 6757028. DOI: 10.1038/s41598-019-50214-z. View

Smyth E, Nilsson M, Grabsch H, van Grieken N, Lordick F . Gastric cancer. Lancet. 2020; 396(10251):635-648. DOI: 10.1016/S0140-6736(20)31288-5. View

Zhang D, He W, Wu C, Tan Y, He Y, Xu B . Scoring System for Tumor-Infiltrating Lymphocytes and Its Prognostic Value for Gastric Cancer. Front Immunol. 2019; 10:71. PMC: 6361780. DOI: 10.3389/fimmu.2019.00071. View

10.

Cologna S, Rosenhouse-Dantsker A . Insights into the Molecular Mechanisms of Cholesterol Binding to the NPC1 and NPC2 Proteins. Adv Exp Med Biol. 2019; 1135:139-160. DOI: 10.1007/978-3-030-14265-0_8. View

11.

Xu Y, Zhang Q, Tan L, Xie X, Zhao Y . The characteristics and biological significance of NPC2: Mutation and disease. Mutat Res Rev Mutat Res. 2019; 782:108284. DOI: 10.1016/j.mrrev.2019.108284. View

12.

Wang Z, Jensen M, Zenklusen J . A Practical Guide to The Cancer Genome Atlas (TCGA). Methods Mol Biol. 2016; 1418:111-41. DOI: 10.1007/978-1-4939-3578-9_6. View

13.

Pernemalm M, De Petris L, Eriksson H, Branden E, Koyi H, Kanter L . Use of narrow-range peptide IEF to improve detection of lung adenocarcinoma markers in plasma and pleural effusion. Proteomics. 2009; 9(13):3414-24. DOI: 10.1002/pmic.200800814. View

14.

Norwood D, Montalvan-Sanchez E, Dominguez R, Morgan D . Gastric Cancer: Emerging Trends in Prevention, Diagnosis, and Treatment. Gastroenterol Clin North Am. 2022; 51(3):501-518. DOI: 10.1016/j.gtc.2022.05.001. View

15.

Dong D, Fang M, Tang L, Shan X, Gao J, Giganti F . Deep learning radiomic nomogram can predict the number of lymph node metastasis in locally advanced gastric cancer: an international multicenter study. Ann Oncol. 2020; 31(7):912-920. DOI: 10.1016/j.annonc.2020.04.003. View

16.

Nshizirungu J, Bennis S, Mellouki I, Sekal M, Benajah D, Lahmidani N . Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients. Dis Markers. 2021; 2021:9980410. PMC: 8342151. DOI: 10.1155/2021/9980410. View

17.

Matsuoka T, Yashiro M . Biomarkers of gastric cancer: Current topics and future perspective. World J Gastroenterol. 2018; 24(26):2818-2832. PMC: 6048430. DOI: 10.3748/wjg.v24.i26.2818. View

18.

Tian S, Peng P, Li J, Deng H, Zhan N, Zeng Z . SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway. Aging (Albany NY). 2020; 12(4):3574-3593. PMC: 7066881. DOI: 10.18632/aging.102831. View

19.

Liao Y, Fang C, Yen C, Hsu S, Wang C, Huang S . Niemann-Pick type C2 protein regulates liver cancer progression via modulating ERK1/2 pathway: Clinicopathological correlations and therapeutical implications. Int J Cancer. 2015; 137(6):1341-51. DOI: 10.1002/ijc.29507. View

20.

Cai H, Dai X, Guo X, Zhang L, Cao K, Yan F . Ataxia telangiectasia mutated inhibitor-loaded copper sulfide nanoparticles for low-temperature photothermal therapy of hepatocellular carcinoma. Acta Biomater. 2021; 127:276-286. DOI: 10.1016/j.actbio.2021.03.051. View