Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2023; 15(11): 1951-1973
Published online Nov 15, 2023. doi: 10.4251/wjgo.v15.i11.1951
Identification of necroptosis-related lncRNAs for prognosis prediction and screening of potential drugs in patients with colorectal cancer
Zhi-Hua Chen, Yi-Lin Lin, Shao-Qin Chen, Xiao-Yu Yang
Zhi-Hua Chen, Shao-Qin Chen, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Zhi-Hua Chen, Shao-Qin Chen, Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, China
Yi-Lin Lin, Peking University People’s Hospital, Beijing 100044, China.
Xiao-Yu Yang, School of Basic Medicine Sciences, Fujian Medical University, Fuzhou 350122, Fujian Province, China
Author contributions: Chen SQ and Yang XY designed this study; Chen ZH analyzed and wrote the manuscript; Lin YL and Chen ZH analyzed the data and completed the RT-PCR experiment; Chen ZH downloaded the data and performed statistical analysis; All the authors have read and approved the final manuscript.
Supported by the Joint Funds for the Innovation of Science and Technology, Fujian Province, No.2019Y9133.
Institutional review board statement: This data of this article was downloaded CRC RNA-Seq data, clinical follow-up information and copy number variation data from the SNP 6.0 chip in the TCGA database from the UCSC cancer browser , and the Gene Expression Omnibus (GEO) database. This study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University (NO. MRCTA, ECFAH of FMU[20190(21)]).
Institutional animal care and use committee statement: This artical had not use any animal, so there isnot need any “Institutional Animal Care and Use Committee Approval Form or Document”.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest related to this work.
Data sharing statement: The datasets generated and analyzed during the current study are available in the TCGA repository [https://portal.gdc.cancer.gov/] and the GEO repository [www.ncbi.nlm.nih.gov/geo/]. We declare that the data and materials used to support the findings of this study are provided and included within the supplementary information files.
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: Xiao-Yu Yang, PhD, Full professor, School of Basic Medicine Sciences, Fujian Medical University, No. 1 Xuefu North Road, Minhou County, Fuzhou 350122, Fujian Province, China. yxyfj@163.com.
Received: May 16, 2023
Peer-review started: May 16, 2023
First decision: August 7, 2023
Revised: August 15, 2023
Accepted: September 14, 2023
Article in press: September 14, 2023
Published online: November 15, 2023
Abstract
BACKGROUND

Tumor recurrence and metastasis lead to a poor prognosis in colorectal cancer (CRC). Necroptosis is closely related to the tumor microenvironment (TME) and affects tumor recurrence and metastasis. We aimed to stratify CRC patients according to necroptosis-related long noncoding RNAs (lncRNAs), which can be used to not only evaluate prognosis and improve precision medicine in clinical practice but also screen potential immunotherapy drugs.

AIM

To stratify CRC patients according to necroptosis-related lncRNAs (NRLs), which can be used to not only evaluate prognosis and improve precision medicine in clinical practice but also screen potential immunotherapy drugs.

METHODS

LncRNA expression profiles were collected from The Cancer Genome Atlas. NRLs were identified by coexpression analysis. Cox regression analysis identified a NRL signature. Then, the value of this signature was comprehensively and multidimensionally evaluated, and its reliability for CRC prognosis prediction was assessed with clinical CRC data and compared with that of six other lncRNA signatures. Gene set enrichment analysis, TME analysis and half-maximal inhibitory concentration (IC50) prediction were also performed according to the risk score (RS) of the signature.

RESULTS

An 8-lncRNA signature significantly associated with overall survival (OS) was constructed, and its reliability was validated with clinical CRC data. Most of the areas under the receiver operating characteristic curves (AUCs) values for 1-, 3- and 5-year OS for this signature were higher than those for the other six lncRNA signatures. OS, disease-specific survival and the progression-free interval were all significantly poorer in the high-risk group. The RS of the signature showed good concordance with the predicted prognosis, with AUCs for 1-, 3- and 5-year OS of 0.79, 0.81 and 0.77, respectively. Additionally, the calibration plots for this signature combined with clinical factors showed that this combination could effectively improve the ability to predict OS. The RS was correlated with tumor stage, lymph node metastasis and distant metastasis. Most of the enriched Kyoto Encyclopedia of Genes and Genomes and Gene Ontology terms were tumor metastasis-related pathways in the high-risk group; these patients showed greater infiltration of immunosuppressive cells, such as cancer-associated fibroblasts, hematopoietic stem cells and M2 macrophages, but less infiltration of infiltrating antitumor effector immune cells, such as cluster of differentiation 8+ T cells and regulatory T cells (Tregs). We explored additional potential immune checkpoint genes and potential immunotherapeutic and chemotherapeutic drugs with relatively low IC50 values.

CONCLUSION

We identified an NRL signature with strong fidelity that could stably predict prognosis and might be an indicator of the TME of CRC. Furthermore, additional potential immunotherapeutic and chemotherapeutic drugs were explored.

Keywords: Long noncoding RNA, Necroptosis, Immunotherapy, Prognosis, Colorectal cancer

Core Tip: An 8-lncRNA signature significantly associated with overall survival (OS) was constructed, and its fidelity was validated in the OS, disease-specific survival and the progression-free interval, it was also validated with clinical colorectal cancer (CRC) data. The risk score which was correlated with tumor stage, lymph node metastasis and distant metastasis in CRC of the signature showed good concordance with the predicted prognosis. The high-risk group showed greater infiltration of immunosuppressive cells, but fewer infiltrating antitumor effector immune cells. We explored additional potential immune checkpoint genes and immunotherapeutic and chemotherapeutic drugs.