Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jan 24, 2024; 15(1): 89-114
Published online Jan 24, 2024. doi: 10.5306/wjco.v15.i1.89
Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes
Kui-Ling Wang, Kai-Di Chen, Wen-Wen Tang, Ze-Peng Chen, Yu-Ji Wang, Guo-Ping Shi, Yu-Gen Chen
Kui-Ling Wang, Kai-Di Chen, Wen-Wen Tang, Ze-Peng Chen, Yu-Ji Wang, Guo-Ping Shi, Yu-Gen Chen, Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Author contributions: Chen YG provided the acquisition of funding and formulated research goals; Wang KL wrote the original manuscript; Chen KD, and Chen ZP were involved in the software analysis; Tang WW, Wang YJ, and Shi GP performed the data collation; All authors have read and agreed to the published version of the manuscript.
Supported by Jiangsu Province Science and Technology Plan Project-Youth Fund Project, No. BK2020040973.
Institutional review board statement: The ethical approval is not applicable to this article.
Informed consent statement: There were no human subjects included in this article, and therefore informed consent is not applicable.
Conflict-of-interest statement: All the authors declare that the study was carried out without any commercial or financial relationships which could be considered a potential conflict of interest.
Data sharing statement: The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.
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: Yu-Gen Chen, Doctor, MD, PhD, Chief Doctor, Professor, Surgeon, Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Qinhuai District, Nanjing 210029, Jiangsu Province, China. yugen.chen@njucm.edu.cn
Received: October 25, 2023
Peer-review started: October 26, 2023
First decision: December 12, 2023
Revised: December 17, 2023
Accepted: January 4, 2024
Article in press: January 4, 2024
Published online: January 24, 2024
Processing time: 89 Days and 18.8 Hours
Abstract
BACKGROUND

A recently hypothesized cause of cell death called disulfidptosis has been linked to the expansion, emigration, and vascular rebuilding of cancer cells. Cancer can be treated by targeting the pathways that trigger cell death.

AIM

To discover the long non-coding RNA of the disulfidaptosis-related lncRNAs (DRLs), prognosis clinical survival, and treat patients with colorectal cancer with medications.

METHODS

Initially, we queried the Cancer Genome Atlas database to collect transcriptome, clinical, and genetic mutation data for colorectal cancer (CRC). Training and testing sets for CRC patient transcriptome data were generated randomly. Key long non-coding RNAs (lncRNAs) related to DRLs were then identified and evaluated using a least absolute shrinkage and selection operator procedure, as well as univariate and multivariate Cox regression models. A prognostic model was then created after risk scoring. Also, Immune infiltration analysis, immune checkpoint analysis, and medication susceptibility analysis were used to investigate the causes of the different prognoses between high and low risk groups. Finally, we validated the differential expression and biomarker potential of risk-predictive lncRNAs through induction using both NCM460 and HT-29 cell lines, as well as a disulfidptosis model.

RESULTS

In this work, eight significant lncRNAs linked to disulfidptosis were found. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of differentially expressed genes between high- and low-risk groups from the prognostic model showed a close relationship with the immune response as well as significant enrichment in neutrophil extracellular trap formation and the IL-17 signaling pathway. Furthermore, significant immune cell variations between the high-risk and low-risk groups were seen, as well as a higher incidence of immunological escape risk in the high-risk group. Finally, Epirubicin, bortezomib, teniposide, and BMS-754807 were shown to have the lowest sensitivity among the four immunotherapy drugs.

CONCLUSION

Our findings emphasizes the role of disulfidptosis in regulating tumor development, therapeutic response, and patient survival in CRC patients. For the clinical treatment of CRC, these important LncRNAs could serve as viable therapeutic targets.

Keywords: Colorectal cancer; Clinical outcomes; Disulfidptosis; Drug sensitivity; Immunotherapy

Core Tip: Disulfidoptosis is a recently identified form of programmed cell death that is being intensely studied in the fields of tumor formation and therapy. Various studies have demonstrated the crucial predictive accuracy of biomarkers linked to disulfidoptosis for the diagnosis and management of cancer. In the mean time, there is increasing confirmation that lncRNA regulates the growth and progression of colorectal cancer (CRC). This study scrutinized out lncRNA closely correlated with disulfidoptosis and assessed its prognostic significance in CRC patients via integrating bioinformatics technology with a clinical patient database.