COL4A1 as a novel oncogene associated with the clinical characteristics of malignancy predicts poor prognosis in glioma

Wang,Hongbo; Liu,Zhendong; Li,Ang; Wang,Jialin; Liu,Jiantao; Liu,Binfeng; Lian,Xiaoyu; Zhang,Bo; Pang,Bo; Liu,Liyun; Gao,Yanzheng

doi:10.3892/etm.2021.10658

COL4A1 as a novel oncogene associated with the clinical characteristics of malignancy predicts poor prognosis in glioma

Authors:
- Hongbo Wang
- Zhendong Liu
- Ang Li
- Jialin Wang
- Jiantao Liu
- Binfeng Liu
- Xiaoyu Lian
- Bo Zhang
- Bo Pang
- Liyun Liu
- Yanzheng Gao
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Affiliations: Department of Orthopedics and Microbiome Laboratory, Henan University People's Hospital, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China, Department of Orthopedics and Microbiome Laboratory, Henan University People's Hospital, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China, Department of Neurosurgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, P.R. China, Department of Orthopaedics, Orthopedic Hospital of Henan Province, Zhengzhou, Henan 450018, P.R. China
Published online on: August 27, 2021 https://doi.org/10.3892/etm.2021.10658
Article Number: 1224
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Studies have indicated that collagen α‑1 (IV) chain (COL4A1) has an indispensable regulatory role in the complex pathological mechanisms of numerous types of malignant tumor. However, its role in the development of glioma has remained elusive. Therefore, the present study sought to determine the association between the expression levels of COL4A1 and the clinical characteristics of gliomas by analyzing large samples. First, analysis of thousands of glioma tissue samples collected from the Gene expression profiling interactive analysis, Gene Expression Omnibus database, the Ivy glioblastoma atlas, The Human Protein Atlas, Chinese Glioma Genome Atlas and The Cancer Genome Atlas. In addition, glioma tissues and normal brain tissues from patients with glioma and epilepsy undergoing surgical resection were collected. These samples, which were subjected to a variety of different detection techniques (including sequencing data, chip data, reverse transcription‑quantitative PCR, cell lines and tissue samples, in situ hybridization and immunology) revealed that COL4A1 expression was not only increased at the mRNA level but also at the protein level as compared with that in normal brain tissue. Furthermore, Kaplan‑Meier analysis revealed that COL4A1 expression was associated with reduced overall survival of patients, particularly those with World Health Organization grade III glioma. Receiver operating characteristic analysis suggested that COL4A1 had a moderate diagnostic value for glioma. In addition, the Mann‑Whitney U‑test or Kruskal‑Wallis test indicated that the expression levels of COL4A1 were positively associated with the histological type and historical grade of the tumor, patient age, ‘Primary, Recurrent, Secondary’ type and the chemotherapy status, and negatively associated with isocitrate dehydrogenase mutation and 1p19q co‑deletion (P<0.001). Gene‑set enrichment analysis indicated that overexpression of COL4A1 promoted cancer‑associated pathways, such as the JAK/STAT signaling pathway and cell cycle regulation. Finally, an MTT assay, immunohistochemical analysis of the cell cycle regulator KI67 and a wound‑healing assay further confirmed that knockdown of COL4A1 inhibited the proliferation and migration ability of glioma cells. In conclusion, COL4A1, as a novel oncogene, is a marker for poor prognosis in patients with glioma. The present study expanded the understanding of the pathogenesis of glioma and identified COL4A1 as a potential target for the diagnosis and treatment of gliomas.

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