Clinical and Translational Research
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2023; 15(6): 1019-1035
Published online Jun 15, 2023. doi: 10.4251/wjgo.v15.i6.1019
Comprehensive analysis of distal-less homeobox family gene expression in colon cancer
Yong-Cheng Chen, Dong-Bing Li, Dong-Liang Wang, Hui Peng
Yong-Cheng Chen, Department of General Surgery (Endoscopic Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Yong-Cheng Chen, Hui Peng, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Yong-Cheng Chen, Hui Peng, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Dong-Bing Li, Dong-Liang Wang, Department of Medicine, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China
Hui Peng, Department of General Surgery (Anorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Author contributions: Chen YC and Peng H participated in study design, and data collection and analysis; Chen YC, Li DB, and Wang DL performed the data analysis; Chen YC and Peng H drafted the manuscript; Chen YC and Peng H revised the manuscript; All authors read and approved the final manuscript.
Institutional review board statement: The current study does not require approval from an ethics committee.
Clinical trial registration statement: This study did not involve a clinical trial registration statement.
Informed consent statement: The data that support the findings of this study are publicly available. The current study does not require signed informed consent documents.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Data sharing statement: All data and material are public.
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 Peng, MD, Chief Doctor, Department of General Surgery (Anorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancun Erheng Road, Tianhe District, Guangzhou 510655, Guangdong Province, China. phui@mail.sysu.edu.cn
Received: January 6, 2023
Peer-review started: January 6, 2023
First decision: January 23, 2023
Revised: February 6, 2023
Accepted: April 27, 2023
Article in press: April 27, 2023
Published online: June 15, 2023
Abstract
BACKGROUND

The distal-less homeobox (DLX) gene family plays an important role in the development of several tumors. However, the expression pattern, prognostic and diagnostic value, possible regulatory mechanisms, and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.

AIM

We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.

METHODS

Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases. Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue. cBioPortal was used to analyze DLX gene family variants. R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map. The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family. The pROC package was used to analyze the diagnostic value of the DLX gene family. R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes. The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration. The ggplot2, the survminer package, and the clusterProfiler package were used for visualization.

RESULTS

DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients. The expression of DLX genes were associated with M stage, pathologic stage, primary therapy outcome, residual tumor, lymphatic invasion, T stage, N stage, age, perineural invasion, and history of colon polyps. DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis. DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways, including the Hippo signaling pathway, the Wnt signaling pathway, several signaling pathways regulating the pluripotency of stem cells, and Staphylococcus aureus infection.

CONCLUSION

The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.

Keywords: Colon cancer, The Cancer Genome Atlas, Distal-less homeobox genes, Prognosis, Immune infiltration

Core Tip: The distal-less homeobox (DLX) gene family plays an important role in the pathogenesis of several tumors. However, the expression pattern, prognostic and diagnostic value, possible regulatory mechanisms, and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported. In this study, we aimed to investigate the expression level, clinical significance, and relationship between DLX genes and immune infiltration in colon cancer to establish an adequate scientific basis for clinical decision making and risk management. The DLX gene family holds promise as a potential diagnostic or prognostic biomarker and therapeutic target for colon cancer.