Estimating disease-free survival of thyroid cancer based on novel cuprotosis-related gene model

Rui Du; Jingting Li; Fang Li; Lusi Mi; Gianlorenzo Dionigi; Hui Sun; Nan Liang

doi:10.3389/fendo.2023.1209172

Estimating disease-free survival of thyroid cancer based on novel cuprotosis-related gene model

Front Endocrinol (Lausanne). 2023 Sep 8:14:1209172. doi: 10.3389/fendo.2023.1209172. eCollection 2023.

Authors

Rui Du¹, Jingting Li¹, Fang Li¹, Lusi Mi¹, Gianlorenzo Dionigi², Hui Sun¹, Nan Liang¹

Affiliations

¹ Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China.
² Department of Pathophysiology and Transplantation, Division of Surgery, Istituto Auxologico Italiano IRCCS (Istituto di Ricovero e Cura a Carattere Scientifco), University of Milan, Milan, Italy.

Abstract

Background: Cuprotosis is a newly discovered form of cell death that differs from other types of cell death. The aim of this study was to investigate the functional role and a possible prognostic model for thyroid cancer.

Methods: TCGA and GEO were used to investigate the differential expression of CRGs in THCA. KEGG and GO enrichment analyses were applied to investigate the possible molecular functions. The features of CRGs were selected by LASSO regression. 20 pairs of samples were randomly collected from the hospital to compare expression between tumor and normal.

Results: Among the 19 CRGs related to thyroid cancer recurrence, 16 genes were differentially expressed in thyroid cancer. KEGG analysis showed that the 19 CRGs were mainly enriched in cell death, cell cycle and ribosomal pathways. K-M survival analysis and subsequent multiple logistic regression revealed that the expression of BUB1 and GINS2 were potential risk factors for disease-free survival (DFS) of thyroid cancer. In addition, further LASSO-regression selected the following three DFS-related CRGs: FDX1, BUB1 and RPL3. A novel prognostic prediction model was constructed by nomogram, and the prediction probability for 1-, 3- and 5-year survival approached the actual time. As for the possible mechanisms, FDX1, BUB1 and RPL3 were associated with immune infiltration. The cell model experiment illustrated that the ATM signaling pathway might be involved in thyroid cancer cell death.

Conclusion: Three CRG models (FDX1, BUB1, RPL3) could better predict the prognosis of thyroid cancer. Immune cell infiltration and the ATM pathway were the possible mechanisms.

Keywords: Cuprotosis; Prognosis; genes; immune cell infiltration; model; survival; thyroid cancer.

Publication types

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

MeSH terms

Cell Cycle
Cell Death
Chromosomal Proteins, Non-Histone
Disease-Free Survival
Humans
Thyroid Neoplasms* / genetics

Substances

GINS2 protein, human
Chromosomal Proteins, Non-Histone

Grants and funding

This study was sponsored by the Jilin Province Science and Technology Development Project [20210402011GH; YDZJ202201ZYTS112]; the project of China-Japan Union Hospital [2023CL01]; and the Project of Jilin Provincial Finance Department [2022SCZ09; 2021SCZ23].