A novel prognostic model based on urea cycle-related gene signature for colorectal cancer

Haiyang Guo; Yuanbiao Wang; Lei Gou; Xiaobo Wang; Yong Tang; Xianfei Wang

doi:10.3389/fsurg.2022.1027655

A novel prognostic model based on urea cycle-related gene signature for colorectal cancer

Front Surg. 2022 Oct 21:9:1027655. doi: 10.3389/fsurg.2022.1027655. eCollection 2022.

Authors

Haiyang Guo¹, Yuanbiao Wang², Lei Gou¹, Xiaobo Wang¹, Yong Tang¹, Xianfei Wang¹

Affiliations

¹ Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
² Department of Yunnan Tumor Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China.

Abstract

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the world. This study aimed to develop a urea cycle (UC)-related gene signature that provides a theoretical foundation for the prognosis and treatment of patients with CRC.

Methods: Differentially expressed UC-related genes in CRC were confirmed using differential analysis and Venn diagrams. Univariate Cox and least absolute shrinkage and selection operator regression analyses were performed to identify UC-related prognostic genes. A UC-related signature was created and confirmed using distinct datasets. Independent prognostic predictors were authenticated using Cox analysis. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts algorithm and Spearman method were applied to probe the linkage between UC-related prognostic genes and tumor immune-infiltrating cells. The Human Protein Atlas database was used to determine the protein expression levels of prognostic genes in CRC and normal tissues. Verification of the expression levels of UC-related prognostic genes in clinical tissue samples was performed using real-time quantitative polymerase chain reaction (qPCR).

Results: A total of 49 DEUCRGs in CRC were mined. Eight prognostic genes (TIMP1, FABP4, MMP3, MMP1, CD177, CA2, S100P, and SPP1) were identified to construct a UC-related gene signature. The signature was then affirmed using an external validation set. The risk score was demonstrated to be a credible independent prognostic predictor using Cox regression analysis. Functional enrichment analysis revealed that focal adhesion, ECM-receptor interaction, IL-17 signaling pathway, and nitrogen metabolism were associated with the UC-related gene signature. Immune infiltration and correlation analyses revealed a significant correlation between UC-related prognostic genes and differential immune cells between the two risk subgroups. Finally, the qPCR results of clinical samples further confirmed the results of the public database.

Conclusion: Taken together, this study authenticated UC-related prognostic genes and developed a gene signature for the prognosis of CRC, which will be of great significance in the identification of prognostic molecular biomarkers, clinical prognosis prediction, and development of treatment strategies for patients with CRC.

Keywords: Gene signature; colorectal cancer; immune infiltration; prognosis; urea cycle.