A Comprehensive Risk Assessment and Stratification Model of Papillary Thyroid Carcinoma Based on the Autophagy-Related LncRNAs

Yongrun Mu; Fuling Song; Kai Yuan; Zili Zhang; Yan Lu; Rongzhan Fu; Dongsheng Zhou

doi:10.3389/fonc.2021.771556

A Comprehensive Risk Assessment and Stratification Model of Papillary Thyroid Carcinoma Based on the Autophagy-Related LncRNAs

Front Oncol. 2022 Feb 24:11:771556. doi: 10.3389/fonc.2021.771556. eCollection 2021.

Authors

Yongrun Mu¹, Fuling Song², Kai Yuan³, Zili Zhang⁴, Yan Lu^{3

5}, Rongzhan Fu³, Dongsheng Zhou³

Affiliations

¹ Department of Head and Neck Surgery Department, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, China.
² Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
³ Department of Thyroid Surgery Department, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
⁴ The Fourth People's Hospital of Jinan, The Third Affiliated Hospital of Shandong First Medical University, Jinan, China.
⁵ Shandong First Medical University, Jinan, China.

Abstract

Background: Papillary thyroid carcinoma (PTC) is one of the most common malignant carcinomas in the endocrine system, and it has a growing incidence worldwide. Despite the development of diagnosis and treatment modalities for thyroid carcinoma, the outcome remains uncertain. Autophagy participates in the process of cancer invasion, malignancy, metastasis, and drug resistance. Emerging research has shown that long noncoding RNAs (lncRNAs) play an important role in the process of different types of cancers. However, the interaction between the process of autophagy and lncRNA and the value of autophagy-related lncRNA for risk assessment, prediction of drug sensitivity, and prognosis prediction in PTC patients remains unknown.

Materials and methods: We screened 1,283 autophagy-related lncRNAs and identified 144 lncRNAs with prognostic value in The Cancer Genome Atlas (TCGA) cohorts. Univariate and multivariate Cox regression analyses were used to establish the prognosis-related autophagy-related lncRNA risk classification consisting of 10 lncRNAs to indicate the level of risk, according to which the patients were grouped into high-risk group and low risk-group.

Results: The high-risk group had dramatically worse overall survival compared with the low-risk group. Cox regression analysis was performed to confirm the independent prognostic value of the autophagy-related lncRNA risk stratification, and the time-dependent receiver operating characteristic curves of the risk stratification were 0.981 (1 year), 0.906 (3 years), and 0.963 (5 years). LncRNA CRNDE (LINC00180) is overexpressed in the tumor, and its high expression matched with poorer survival state. So, we chose it for further experiment. Finally, knockdown of the CRNDE in PTC increased the sensitivity to sorafenib.

Conclusion: Collectively, we successfully established a novel risk stratification for PTC based on the expression profiles of autophagy-related lncRNAs.

Keywords: Autophagy; LncRNA; Papillary thyroid carcinoma; Prognosis; Sorafenib.