Investigating the Diagnostic and Therapeutic Potential of SREBF2-Related Lipid Metabolism Genes in Colon Cancer

Abstract

Purpose

Colon cancer is one of the leading causes of death worldwide, and screening of effective molecular markers for the diagnosis is prioritised for prevention and treatment. This study aimed to investigate the diagnostic and predictive potential of genes related to the lipid metabolism pathway, regulated by a protein called sterol-regulatory element-binding transcription Factor 2 (SREBF2), for colon cancer and patient outcomes.

Methods

We used machine-learning algorithms to identify key genes associated with SREBF2 in colon cancer based on a public database. A nomogram was created to assess the diagnostic value of these genes and validated in the Cancer Genome Atlas. We also analysed the relationship between these genes and the immune microenvironment of colon tumours, as well as the correlation between gene expression and clinicopathological characteristics and prognosis in the China Medical University (CMU) clinical cohort.

Results

Three genes, 7-dehydrocholesterol reductase (DHCR7), hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2), and Ral guanine nucleotide dissociation stimulator-like 1 (RGL1), were identified as hub genes related to SREBF2 and colon cancer. Using the TCGA dataset, receiver operating characteristic curve analysis showed the area under the curve values of 0.943, 0.976, and 0.868 for DHCR7, HSD11B2, and RGL1, respectively. In the CMU cohort, SREBF2 and DHCR7 expression levels were correlated with TNM stage and tumour invasion depth (P < 0.05), and high DHCR7 expression was related to poor prognosis of colon cancer (P < 0.05). Furthermore, DHCR7 gene expression was positively correlated with the abundance of M0 and M1 macrophages and inversely correlated with the abundance of M2 macrophages, suggesting that the immune microenvironment may play a role in colon cancer surveillance. There was a correlation between SREBF2 and DHCR7 expression across cancers in the TCGA database.

Conclusion

This study highlights the potential of DHCR7 as a diagnostic marker and therapeutic target for colon cancer.

Keywords:

• colon cancer
• sterol-regulatory element-binding transcription Factor 2
• SREBF2
• 7-dehydrocholesterol reductase
• DHCR7
• diagnosis
• machine learning

Data Sharing Statement

The GEO and TCGA datasets used in this study can be found at http://www.ncbi.nlm.nih.gov/geo/ and https://portal.gdc.cancer.gov/.

Ethics Approval and Informed Consent

The study received ethics approval from the Medical Ethics Committee of the First Hospital of China Medical University (Reference No. 2022157). All procedures involving human individuals in our study were performed in accordance with the Declaration of Helsinki. Informed consent was sought and acquired from all patients before the colon cancer specimens were obtained.

Acknowledgments

The authors thank Dr. Shipeng Guo (M.D.) and the team for providing the web resource GPSAdb (http://guotosky.vip:13838/GPSA/).

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the Social Development Program from Shenyang Science and Technology Bureau, China (No. F20-205-4-033).