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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Kinesin family member 14 expression and its clinical implications in colorectal cancer
Kai Qin, Jia-Yuan Luo, Da-Tong Zeng, Wan-Ying Huang, Bin Li, Qi Li, Yan-Ting Zhan, Rong-Quan He, Wei-Jian Huang, Gang Chen, Zu-Yuan Chen, Bang-Teng Chi, Yu-Xing Tang, Rui-Xue Tang, Hui Li
Kai Qin, Jia-Yuan Luo, Wan-Ying Huang, Bin Li, Qi Li, Yan-Ting Zhan, Gang Chen, Zu-Yuan Chen, Bang-Teng Chi, Yu-Xing Tang, 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
Hui Li, Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-first authors: Kai Qin and Jia-Yuan Luo.
Co-corresponding authors: Rui-Xue Tang and Hui Li.
Author contributions: Qin K, Luo JY, Tang RX and Li H conceived and designed the study; Zeng DT, Huang WY, Li B and Li Q analyzed the data and performed all the graphs; Zhan YT, He RQ, Huang WJ, Chen G, Chen ZY, Chi BT and Tang YX conducted the experiments; Qin K and Luo JY drafted the manuscript; Tang RX and Li H revised the manuscript. The decision for co-first authorship is based on the substantial and equal contributions of Qin K and Luo JY to the conception, design, execution, and interpretation of the research presented in this manuscript. The designation of co-corresponding authors, Tang RX and Li H, is attributed to their shared responsibility in overseeing the submission, revision, and communication aspects of this work with the journal. All authors have played a crucial role in drafting and revising the manuscript and have approved the final version.
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; Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project, No. Z-A20220415; Guangxi Medical University Teacher Teaching Ability Development Project, No. 2022JFA02; and Guangxi Medical University Undergraduate Education and Teaching Reform Project, No. 2023Y05.
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.
Data sharing statement: The data was available from the corresponding author at
lihui_gxmu@163.com.
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: Hui Li, Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
lihui_gxmu@163.com
Received: October 28, 2024
Revised: November 22, 2024
Accepted: December 25, 2024
Published online: March 15, 2025
Processing time: 111 Days and 20.1 Hours
BACKGROUND
Colorectal cancer (CRC) is the third most common cancer globally, causing over 900000 deaths annually. Risk factors include aging, diet, obesity, sedentary lifestyle, tobacco use, genetic predisposition, and inflammatory bowel disease. Despite current treatments, survival rates for advanced CRC remain low, highlighting the need for better therapeutic strategies.
AIM
To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14 (KIF14) expression within CRC specimens. Additionally, this study aims to investigate the interaction between nitidine chloride (NC) and KIF14, considering their potential as therapeutic targets.
METHODS
The expression of the KIF14 protein in CRC was analyzed using immunohistochemical staining. The integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference (SMD) for KIF14 mRNA levels. The assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves, along with measures of sensitivity, specificity, and likelihood ratios. Additionally, clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in CRC. Survival analysis established the prognostic value of KIF14 in CRC. The molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis, and molecular docking was utilized to explore the targeting affinity between NC and KIF14.
RESULTS
KIF14 was highly expressed in 208 CRC patients. Data from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples, with an SMD of 1.92 (95%CI: 1.49-2.35). The area under the curve was 0.94 (95%CI: 0.92-0.96), with a sensitivity of 0.85 (95%CI: 0.78-0.90) and a specificity of 0.90 (95%CI: 0.85-0.93). The positive and negative likelihood ratios were 8.38 (95%CI: 5.39-13.02) and 0.17 (95%CI: 0.11-0.26), respectively. At the single-cell level, significant overexpression of KIF14 was observed in CRC cells (P < 0.001), with 35 CRC cell lines dependent on KIF14 for growth. The K-M plots demonstrated that KIF14 possesses prognostic value in CRC patients within the GSE71187 and GSE103679 datasets (P < 0.05). Binding energy calculations indicated that KIF14 is a potential target for NC (binding energy: 10.3 kcal/mol).
CONCLUSION
KIF14 promotes the growth of CRC cells and acts as an oncogenic factor, potentially serving as a therapeutic target for NC in the treatment of CRC.
Core Tip: This study evaluates the clinical and pathological significance of Kinesin family member 14 (KIF14) in colorectal cancer (CRC) and explores its interaction with nitidine chloride (NC) as a potential therapeutic target. High KIF14 expression in CRC was confirmed through immunohistochemistry and multiplatform mRNA analysis, with significant diagnostic accuracy. Clustered regularly interspaced short palindromic repeats screening and single-cell sequencing validated KIF14’s role in CRC cell growth. Survival analysis highlighted KIF14’s prognostic value. Molecular docking revealed a strong binding affinity between NC and KIF14, suggesting that KIF14 is a promising target for NC in CRC treatment.
