Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2024; 16(2): 314-330
Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.314
Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer
Lei Zheng, Jia Lu, Da-Lu Kong
Lei Zheng, Da-Lu Kong, Department of Colorectal Cancer Surgery, National Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy of Tianjin, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
Jia Lu, Department of Infection Management, National Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy of Tianjin, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
Co-first authors: Lei Zheng and Jia Lu.
Author contributions: Kong DL conceived and designed the study; Zheng L provided study materials and collected and assembled data; Lu J analyzed data and prepared figures; Zheng L and Lu J wrote the manuscript and contributed equally to the study and as such are co-first authors; All authors read and approved the final manuscript.
Supported by the Science and Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2020KJ133; and Tianjin Key Medical Discipline (Specialty) Construction Project, No. TJYXZDXK-009A.
Institutional review board statement: The present study was approved by the Ethics Committee of Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) (Approval No. Ek2019085). All methods were performed in accordance with relevant guidelines and regulations.
Clinical trial registration statement: Our study is purely observational in nature and does not involve any intervention. As such, it falls under the category of observational research rather than interventional research. Consequently, there was no clinical trial registration undertaken for this study.
Informed consent statement: Written informed consent for publication was obtained from all participants.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study are openly available in The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/repository?facetTab=cases&filters =%7B%22op%22%3A%22and%22%2C%22content%22%3A%5B%7B%22op%22%3A%22in%22%2C%22content%22%3A%7B%22field%22%3A%22cases.project.project_id%22%2C%22value%22%3A%5B%22TCGA-COAD%22%2C%22TCGA-READ%22%5D%7D%7D%5D%7D). Data from clinical samples were not uploaded to the database.
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: Da-Lu Kong, PhD, Doctor, Department of Colorectal Cancer Surgery, National Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy of Tianjin, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, No. 1 Huanhuxi Road Hexi District, Tianjin 300060, China. kongdalu_1@163.com
Received: October 11, 2023
Peer-review started: October 12, 2023
First decision: October 28, 2023
Revised: December 12, 2023
Accepted: January 5, 2024
Article in press: January 5, 2024
Published online: February 15, 2024
Processing time: 114 Days and 6.1 Hours
ARTICLE HIGHLIGHTS
Research background

Cyclin-dependent kinase 9 (CDK9) expression and autophagy in colorectal cancer (CRC) tissues has not been widely studied. CDK9, a key regulator of transcription, may influence the occurrence and progression of CRC. The expression of autophagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC.

Research motivation

Under normal physiological conditions, autophagy can inhibit tumorigenesis, but once a tumor forms, autophagy may promote tumor growth. Therefore, understanding the relationship between autophagy and cancer, particularly how autophagy promotes tumor growth after its formation, is a key motivation for this research.

Research objectives

To investigate the relationship between CDK9 expression and autophagy in CRC, assess differences in autophagy between left and right colon cancers, and analyze the associations of autophagy-related genes with clinical features and prognosis.

Research methods

The research utilized a multi-faceted approach involving data analysis from The Cancer Genome Atlas database to study CDK9 expression in CRC. We also collected fresh tumor and paracarcinoma tissues for electron microscopy, immunohistochemistry, and flow cytometry to investigate autophagy. Additionally, the study analyzed the expression of autophagy-related genes BECN1 and ABCG2 and their correlation with clinical features and prognosis.

Research results

CDK9 expression was increased in CRC tissues. CDK9 expression positively correlated with the level of autophagy in colon cancer, indicating a potential link between CDK9 and autophagy in cancer progression. The incidence of autophagy was also found to be significantly higher in right colon cancer compared to left colon cancer with primary liver metastasis. Right colon cancer displayed a higher expression of ABCG2, suggesting a potential mechanism for the observed differences in prognosis between left and right colon cancers. High expression of CDK9 was found to be associated with a poor prognosis in CRC, affecting overall survival, disease-specific survival, and progression-free interval. The expression of CDK9 was linked to specific clinical features such as tumor T-stage and lymph node invasion. Finally, high expressions of ABCG2 and BECN1 were also associated with specific clinical features, and expression levels of ABCG2 had a high predictive accuracy for CRC prognosis.

Research conclusions

CDK9 expression positively correlated with the level of autophagy in colon cancer. Thus, this study has laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of tumor patients.

Research perspectives

This study emphasized the significance of patient-specific treatment approaches in CRC cancer, highlighting the role of CDK9, autophagy, and drug resistance factors in prognosis. It underscored the need for combination therapies and further research to improve cancer treatment outcomes.