High expression of stearoyl-coenzyme A desaturase in colorectal cancer oncogenic functions and its potential as a therapeutic target.

Abstract

Background: The stearoyl-coenzyme A desaturase (SCD) gene influences colorectal cancer (CRC) pathogenesis, with its expression linked to tumor cell survival and resistance, necessitating further investigation into its role in CRC.

Aim: To explore the clinical and pathological significance of SCD expression in CRC tissues and to evaluate the affinity between nitidine chloride (NC) and SCD as a target.

Methods: Multi-center high-throughput data related to CRC were integrated to calculate the standardized mean difference of SCD mRNA expression levels. Immunohistochemical staining results, Clustered Regularly Interspaced Short Palindromic Repeats knockout screening results of cell growth, and single-cell sequencing were employed to verify the significance of SCD expression in CRC. The clinical and pathological significance of SCD was assessed using pooled receiver operating characteristic curves, sensitivity, specificity, and likelihood ratios. The molecular mechanism of NC against CRC was clarified using the SwissTarget Prediction and functional enrichment, and molecular docking techniques were utilized to explore the targeting affinity between NC and SCD.

Results: Data from 18 platforms, including 2482 CRC samples and 1334 non-cancerous colorectal tissue controls. SCD expression was significantly upregulated in CRC, with a standardized mean difference of 2.05 [95% confidence interval (CI): 1.69-2.41]. The area under the pooled receiver operating characteristic curve was 0.95 (95%CI: 0.92-0.96), with a sensitivity of 0.86 (95%CI: 0.81-0.90) and a specificity of 0.90 (95%CI: 0.87-0.93). Positive and negative likelihood ratios were 9.02 (95%CI: 6.49-12.51) and 0.15 (95%CI: 0.10-0.22), respectively. High SCD protein expression was noted in 208 CRC patients, significantly associated with vascular invasion (P < 0.001). At the single-cell level, SCD was significantly overexpressed in CRC cells (P < 0.001). A total of 33 CRC cell lines depended on SCD for growth. The potential mechanism of NC against CRC might involve modulation of the cell cycle, positioning SCD as a potential target for NC.

Conclusion: SCD promotes CRC cell growth and thus acts as an oncogenic factor, making it a potential therapeutic target for NC in CRC treatment.