Lu XF, Zhang HW, Chang X, Guo YZ. F-box protein 22: A prognostic biomarker for colon cancer associated with immune infiltration and chemotherapy resistance. World J Gastrointest Oncol 2025; 17(4): 102913 [DOI: 10.4251/wjgo.v17.i4.102913]
Corresponding Author of This Article
Yong-Ze Guo, MD, Professor, Department of Gastroenterology, Affiliated Hospital of Hebei Engineering University, No. 81 Congtai Road, Congtai District, Handan 056002, Hebei Province, China. guoyongze69@126.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Xiao-Fei Lu, Department of Clinical Medicine, Hebei University of Engineering, Handan 056002, Hebei Province, China
Hong-Wei Zhang, Xiao Chang, Yong-Ze Guo, Department of Gastroenterology, Affiliated Hospital of Hebei Engineering University, Handan 056002, Hebei Province, China
Co-first authors: Xiao-Fei Lu and Hong-Wei Zhang.
Author contributions: Lu XF and Zhang HW contributed equally to this manuscript as co-first authors. Lu XF, Zhang HW, Chang X, and Guo YZ designed and coordinated the study, drafted the manuscript, and interpreted the data; Lu XF, Zhang HW, and Chang X performed the experiments, acquired and analyzed data; and all authors providing their approval for the final version of the article.
Institutional review board statement: The study was reviewed and approved by institutional ethics board of Affiliated Hospital of Hebei Engineering University (No.: 2024[K]005-01).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data are available from the corresponding author upon reasonable request.
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: Yong-Ze Guo, MD, Professor, Department of Gastroenterology, Affiliated Hospital of Hebei Engineering University, No. 81 Congtai Road, Congtai District, Handan 056002, Hebei Province, China. guoyongze69@126.com
Received: November 28, 2024 Revised: January 10, 2025 Accepted: February 21, 2025 Published online: April 15, 2025 Processing time: 117 Days and 9.4 Hours
Abstract
BACKGROUND
Colon cancer represents a significant malignant neoplasm within the digestive system, characterized by a high incidence rate and substantial disease burden. The F-box protein 22 (FBXO22) plays a role in forming a specific type of ubiquitin ligase subunit, which is expressed abnormally in various malignant neoplasms and shows a notable relationship with prognosis in patients with cancer. Nevertheless, the function of FBXO22 in the context of colon cancer remains inadequately elucidated.
AIM
To explore the role of FBXO22 in colon cancer by examining FBXO22 expression patterns and analyzing how the protein affects the prognosis in patients who have undergone surgery.
METHODS
Samples of cancerous and nearby normal tissues from patients with colon cancer were gathered, along with pertinent clinical data. Expression levels of the FBXO22 gene in both cancerous and paracancerous tissues were assessed through immunohistochemistry. The median H score served as a criterion for categorizing FBXO22 gene expression into high and low levels in cancerous tissues, and the relationship between these expression levels and various pathologic characteristics of patients, such as age, sex, and clinical stage, was analyzed. Colon cancer cell lines HCT116 and DLD-1 were used and divided into three groups: A blank control group, a negative control group, and a si-FBXO22 group. FBXO22 gene mRNA and protein expression were measured 24 hours post-transfection using real-time fluorescence quantitative polymerase chain reaction and western blotting. The proliferation capabilities of the cells in each group were assessed using the Cell Counting Kit-8 assay and 5-ethynyl-2’-deoxyuridine assay, while cellular migration and invasion abilities were evaluated using scratch healing and Transwell assays. Various online platforms, including the Timer Immune Estimation Resource, were used to analyze pan-cancer expression, promoter methylation levels, and mutation frequencies of the FBXO22 gene in colon cancer patients. Additionally, the correlation between FBXO22 gene expression, patient prognosis, immune cell infiltration, and the expression of immune molecules in the colon cancer microenvironment was investigated. The relationship between FBXO22 gene expression and chemotherapy resistance, along with the potential mechanisms of action of the FBXO22 gene, were analyzed using The Cancer Genome Atlas dataset and the Genomics of Drug Sensitivity in Cancer drug training set via R software.
RESULTS
Compared with normal colonic tissues, the FBXO22 gene was highly expressed in colon cancer tissues. Post-operative patients with colon cancer elevated FBXO22 reduced survival and exhibited resistance to various chemotherapeutic agents. FBXO22 expression suppresses the infiltration of anti-tumor immune cells. In vitro, FBXO22 knockdown inhibited the proliferation and migration of colon cancer cells.
CONCLUSION
The FBXO22 gene is a biomarker of poor prognosis in patients with colon cancer and has potential as a target for immunotherapy and overcoming chemotherapy resistance.
Core Tip: The precise role of the F-box protein 22 (FBXO22) gene in post-operative colon cancer patients remains to be fully elucidated. Utilizing bioinformatics assessments alongside cellular experimentation, researchers observed that the expression of the FBXO22 gene is markedly higher in colon cancer tissues when compared to normal colonic tissues. Patients suffering from colon cancer who present with increased FBXO22 gene levels tend to have decreased survival rates and show resistance to various chemotherapy agents. The elevated levels of the FBXO22 gene are associated with a reduction in the infiltration of immune cells that target tumors. Laboratory experiments demonstrate that reducing the activity of the FBXO22 gene hinders the growth and movement of colon cancer cells. The evidence suggests that the FBXO22 gene may facilitate the advancement of colon cancer, be associated with the onset of resistance to chemotherapy among post-operative colon cancer patients, and could act as an indicator of poor outcomes for these individuals. Consequently, targeting FBXO22 could represent a novel approach for treating colon cancer.
