GCNT4 is Associated with Prognosis and Suppress Cell Proliferation in Gastric Cancer

Hui Sun; Jinjia Chang; Min Ye; Weiwei Weng; Meng Zhang; Shujuan Ni; Cong Tan; Dan Huang; Lei Wang; Xiang Du; Mi-Die Xu; Weiqi Sheng

doi:10.2147/OTT.S248997

GCNT4 is Associated with Prognosis and Suppress Cell Proliferation in Gastric Cancer

Onco Targets Ther. 2020 Aug 25:13:8601-8613. doi: 10.2147/OTT.S248997. eCollection 2020.

Authors

Hui Sun^#^{1

2}, Jinjia Chang^#^{3

4}, Min Ye^#^{1

3

5}, Weiwei Weng^{1

3

5}, Meng Zhang^{1

3

5}, Shujuan Ni^{1

3

5}, Cong Tan^{1

3

5}, Dan Huang^{1

3

5}, Lei Wang^{1

3

5}, Xiang Du^{1

3

5}, Mi-Die Xu^{1

3

5}, Weiqi Sheng^{1

3

5}

Affiliations

¹ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, People's Republic of China.
² Department of Pathology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai 200031, People's Republic of China.
³ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
⁴ Department of Medical Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, People's Republic of China.
⁵ Institute of Pathology, Fudan University, Shanghai 200032, People's Republic of China.

^# Contributed equally.

Abstract

Background: GCNT4 is a member of the glucosaminyl (N-acetyl) transferases family that has been implicated in multiple human malignancies. However, the role of GCNT4 in gastric cancer (GC) is unknown. In this present study, we aimed to explore the role and clinicopathological correlation of GCNT4 in GC.

Materials and methods: We first evaluated the dysregulation of GCNT4 in The Cancer Genome Atlas (TCGA) and then we performed RT-qPCR and immunohistochemistry to validate the results in a cohort of in-house patients. The clinicopathological correlation and function of GCNT4 in GC were also analysed.

Results: GCNT4 was found to be significantly downregulated in GC. In addition, GCNT4 expression correlated with tumour depth, nervous invasion and pathological tumor-node-metastasis (pTNM) stage. Moreover, lower GCNT4 levels conferred poor overall survival (OS) and disease-free survival (DFS) to GC patients. Multivariate Cox regression analysis revealed that GCNT4 protein expression is an independent prognostic factor for OS in patients with GC. Further functional experimental results revealed that overexpression of GCNT4 appears to halt GC cell proliferation and the cell cycle.

Conclusion: Altogether, these findings indicated that GCNT4 regulates the GC cell cycle and have important implications for the selection of therapeutic targets to prevent tumour proliferation.

Keywords: GCNT4; cell cycle; dysregulation; gastric cancer; prognosis.

Grants and funding

This work was supported by National Natural Science Foundation of China (81972249, 81602078, 81472220, 81802367, 81802361), Shanghai Science and Technology Development Fund (18ZR1408000, 17ZR1406500 and 15ZR1407400), Shanghai Science and technology development fund (19MC1911000), Clinical Research Project of Shanghai Municipal Health Committee (20194Y0348), National Key R&D Program of China (2017YFC1311004), National Human Genetic Resources Sharing Service Platform (2005DKA21300), and Hospital Foundation of Fudan University Shanghai Cancer Center (YJMS201907, YJ201704).