Construction and validation of a PANoptosis-related lncRNA signature for predicting prognosis and targeted drug response in thyroid cancer

Ruowen Li; Mingjian Zhao; Min Sun; Chengxu Miao; Jinghui Lu

doi:10.7717/peerj.15884

Construction and validation of a PANoptosis-related lncRNA signature for predicting prognosis and targeted drug response in thyroid cancer

PeerJ. 2023 Sep 1:11:e15884. doi: 10.7717/peerj.15884. eCollection 2023.

Authors

Ruowen Li^{1

2}, Mingjian Zhao^{1

2}, Min Sun^{1

2}, Chengxu Miao^{1

2}, Jinghui Lu¹

Affiliations

¹ Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
² School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Abstract

Thyroid cancer (TC) is the most prevalent malignancy of the endocrine system. PANoptosis, a newly discovered cell death pathway, is of interest in tumor research. However, the relationship between PANoptosis-related lncRNAs (PRlncRNAs) and TC remains unclear. The study aimed to develop a prognostic model based on PRlncRNAs in TC. Gene expression data of PANoptosis-associated genes and clinical information on TC from The Cancer Genome Atlas (TCGA) database were analyzed by Pearson correlation analysis, univariate/multivariate Cox analysis, and Lasso Cox regression analysis. A PRlncRNA signature was constructed and used to develop a nomogram to predict overall survival (OS). We further explored the correlation between the risk score and tumor immune microenvironment, immune checkpoints, and drug sensitivity. Moreover, we verified the expression and biological function of lncRNAs in TC cell lines. Finally, seven PRlncRNAs were used to construct a prognostic model for predicting the OS of TC patients. We found that the risk score was associated with the tumor microenvironment (TME) and the expression of critical immune checkpoints. In addition, we screened for drugs that high- or low-risk TC groups might be sensitive to. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed differential expression of four PRlncRNAs (GAPLINC, IDI2-AS1, LINC02154, and RBPMS-AS1) between tumor and normal tissues. Besides, a GEO database (GSE33630) was used to verify the expression differences of PRLncRNAs in THCA tissues and normal tissues. Finally, RBPMS-AS1 was found to inhibit the proliferation and migration of TC cells. In conclusion, we developed a PANoptosis-related lncRNA prognostic risk model that offers a comprehensive understanding of TME status in patients with TC and establishes a foundation for the choice of sensitive medications and immunotherapy.

Keywords: Drug response; Long non-coding RNA (lncRNA); Migration; PANoptosis; Prognosis; Proliferation; Thyroid cancer (TC); Tumor immune microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Death
Humans
Nomograms
Prognosis
RNA, Long Noncoding*
Thyroid Neoplasms*
Tumor Microenvironment

Substances

RNA, Long Noncoding

Grants and funding

This study was supported by grants from the Natural Science Foundation of Shandong Province (No. ZR2021LZL003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.