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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
High expression of stearoyl-coenzyme A desaturase in colorectal cancer oncogenic functions and its potential as a therapeutic target
Xiao-Wei Wang, Wan-Ying Huang, Kai Qin, Da-Tong Zeng, Zu-Yuan Chen, Bang-Teng Chi, Yu-Xing Tang, Qi Li, Bin Li, Dong-Ming Li, Rong-Quan He, Wei-Jian Huang, Gang Chen, Rui-Xue Tang, Zhen-Bo Feng
Xiao-Wei Wang, Wan-Ying Huang, Kai Qin, Zu-Yuan Chen, Bang-Teng Chi, Yu-Xing Tang, Qi Li, Bin Li, Dong-Ming Li, Gang Chen, Zhen-Bo Feng, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Da-Tong Zeng, Wei-Jian Huang, Department of Pathology, Redcross Hospital of Yulin City, Yulin 537000, Guangxi Zhuang Autonomous Region, China
Rong-Quan He, Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Rui-Xue Tang, Department of Pathology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250000, Shandong Province, China
Co-first authors: Xiao-Wei Wang and Wan-Ying Huang.
Co-corresponding authors: Rui-Xue Tang and Zhen-Bo Feng.
Author contributions: Wang XW, Huang WY, Tang RX, and Feng ZB conceived and designed the study; Qin K, Zeng DT, Chen ZY, Chi BT, and Tang YX analyzed the data and performed all the graphs; Li Q, Li B, Li DM, He RQ, Huang WJ, and Chen G provided technical support and experimental materials; Wang XW and Huang WY drafted the manuscript; Tang RX and Feng ZB revised the manuscript. The decision for co-first authorship is based on the substantial and equal contributions of Wang XW and Huang WY to the conception, design, execution, and interpretation of the research presented in this manuscript. Both authors have played a crucial role in drafting and revising the manuscript and have approved the final version. The designation of co-corresponding authors, Tang RX and Feng ZB are attributed to their shared responsibility in overseeing the submission, revision, and communication aspects of this work with the journal. Both authors actively participated in the development of the manuscript and are equally accountable for its content.
Supported by Natural Science Foundation of Shandong Province, No. ZR2020QH185; Scientific Research Nurturing Fund of the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. QYPY2020NSFC0803; and Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project, No. Z20210442.
Institutional review board statement: The protocol for this research project has been approved by a suitably constituted Ethics Committee of Yulin Red Cross Hospital, approval No. Z20210442.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Zhen-Bo Feng, PhD, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
fengzhenbo_gxmu@163.com
Received: August 10, 2024
Revised: October 8, 2024
Accepted: December 4, 2024
Published online: February 27, 2025
Processing time: 164 Days and 17.4 Hours
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.
Core Tip: Stearoyl-coenzyme A desaturase (SCD) is markedly upregulated in colorectal cancer (CRC), highlighting its role as an oncogenic factor and suggesting its potential as a therapeutic target. Our extensive analysis across multiple centers reveals that the increased SCD expression is closely associated with CRC progression and vascular invasion. Nitidine chloride, targeting SCD, shows promise in CRC treatment by potentially modulating the cell cycle. This study provides robust statistical evidence supporting SCD as a critical factor in CRC pathology and a viable target for effective therapeutic strategies.
