Pan-cancer analysis combined with experiments predicts CTHRC1 as a therapeutic target for human cancers

Dazhao Peng; Cheng Wei; Xiaoyang Zhang; Shenghui Li; Hao Liang; Xingyu Zheng; Shulong Jiang; Lei Han

doi:10.1186/s12935-021-02266-3

Pan-cancer analysis combined with experiments predicts CTHRC1 as a therapeutic target for human cancers

Cancer Cell Int. 2021 Oct 26;21(1):566. doi: 10.1186/s12935-021-02266-3.

Authors

Dazhao Peng¹, Cheng Wei¹, Xiaoyang Zhang¹, Shenghui Li¹, Hao Liang¹, Xingyu Zheng², Shulong Jiang³, Lei Han⁴

Affiliations

¹ Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
² Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, China.
³ Clinical Medical Laboratory Center, Jining First People's Hospital, Jining Medical University, Jiankang Road, Jining, Shandong, 272000, People's Republic of China. jnsljiang@163.com.
⁴ Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. superhanlei@tmu.edu.cne.

Abstract

Background: The function of collagen triple helix repeat containing 1 (CTHRC1) as an oncogene has been reported in a growing number of publications. Bioinformatics methods represent a beneficial approach to examine the mechanism and function of the CTHRC1 gene in the disease process of cancers from a pan-cancer perspective.

Methods: In this study, using the online databases UCSC, NCBI, HPA, TIMER2, Oncomine, GEPIA, UALCAN, cBioPortal, COSMIC, MEXPRESS, STRING, CCLE, LinkedOmics, GTEx, TCGA, CGGA, and SangerBox, we focused on the relationship between CTHRC1 and tumorigenesis, progression, methylation, immunity, and prognosis. qPCR was used to detect CTHRC1 expression in glioma tissues and cell lines.

Results: The pan-cancer analysis showed that CTHRC1 was overexpressed in most tumors, and a significant correlation was observed between CTHRC1 expression and the prognosis of patients with cancer. CTHRC1 genetic alterations occur in diverse tumors and are associated with tumor progression. Levels of CTHRC1 promoter methylation were decreased in most cancer tissues compared with normal tissues. In addition, CTHRC1 coordinated the activity of ICP genes through diverse signal transduction pathways, was also associated with immune cell infiltration and the tumor microenvironment, and potentially represented a promising immunotherapy target. We identified CTHRC1-related genes across cancers using the GEPIA2 tool. The single-gene GO analysis of CTHRC1 across cancers showed that it was involved in some signaling pathways and biological processes, such as the Wnt signaling pathway, cell migration, and positive regulation of protein binding. The expression and function of CTHRC1 were also further verified in glioma tissues and cell lines.

Conclusions: CTHRC1 is overexpressed in various cancer types and functions as an important oncogene that may promote tumorigenesis and development through different mechanisms. CTHRC1 may represent an important therapeutic target for human cancers.

Keywords: CTHRC1; Expression; Immune; Methylation; Pan-cancer; Prognosis.

Abstract

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