Procollagen C-protease enhancer protein is a prognostic factor for glioma and promotes glioma development by regulating multiple tumor-related pathways and immune microenvironment

Author:

Zhao Zijun1,Zhao Jiahui2,Wang Zairan1,Wu Yue3,Zhang Zhanzhan1,Song Zihan1,Miao Jihao1,Liu Boheng4,Zhang Shiyang1,Sun Boyu1,Zhao Zongmao1ORCID

Affiliation:

1. Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China

2. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

3. Department of Neurology, The Second Hospital of Hebei Medical University, Hebei, Shijiazhuang, China

4. Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Hebei, Shijiazhuang, China

Abstract

Objectives Glioma is a common type of brain tumor with high incidence and mortality rates. Procollagen C-protease enhancer protein (PCOLCE) has been shown to regulate tumor growth and metastasis in several cancers. However, the role of PCOLCE in glioma is unknown. This study aims to assess the association between PCOLCE and prognosis of glioma, and investigated the potential mechanisms. Methods The prognostic value of PCOLCE was determined using data from nine publicly available glioma cohorts. We also investigated the relationship between PCOLCE and glioma immune microenvironment and predicted response to immunotherapy based on the expression levels of PCOLCE. The potential roles of PCOLCE in glioma were also explored and validated in cell experiment. Results Survival analysis suggested that high-PCOLCE expression was associated with poor prognosis in glioma. Upregulation of PCOLCE enhanced an immune suppressive microenvironment in glioma by regulating immunocyte infiltration and Cancer-Immunity Cycle. Cox and ROC analysis revealed that PCOLCE was a prognostic factor for glioma and could be used to predict survival of the patients. Patients with low-PCOLCE expression were more likely to respond to Immunotherapy with ICI (immune checkpoint inhibitor) and survive longer. Enrichment analysis showed that PCOLCE was associated with multiple tumor-related pathways. Finally, we demonstrated that the knockdown of PCOLCE inhibited glioma development by regulating cell cycle and promoting apoptosis in in vitro experiments. Conclusion PCOLCE promotes glioma progression by regulating multiple tumor-related pathways and immune microenvironment and can be used as a prognostic factor for glioma.

Funder

National Natural Science Foundation of China

National Key R & D Program Intergovernmental Cooperation on International Scientific and Technological Innovation of the Ministry of Science and Technology of China

Hebei Natural Science Foundation General Project--- Beijing-Tianjin-Hebei Basic Research Cooperation Project

Special Project for the Construction of Hebei Province International Science and Technology Cooperation Base

Government funded Project on Training of outstanding Clinical Medical Personnel and Basic Research Projects of Hebei Province in the Year of 2017

Government funded Project on Training of outstanding Clinical Medical Personnel and Basic Research Projects of Hebei Province in the Year of 2019

Publisher

SAGE Publications

Subject

Pharmacology,Immunology,Immunology and Allergy,Pharmacology,Immunology,Immunology and Allergy

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