The Prognostic Value and Potential Immune Mechanisms of lncRNAs Related to Immunogenic Cell Death in Papillary Thyroid Carcinoma

Yixian Wang,1,* Xin Li,2,* Yinde Huang,3,* Qingwei Gang,1 Mingyu Liu,1 Han Zhang,1 Shikai Shen,1 Yao Qi,1 Jian Zhang1 1Department of Vascular and Thyroid Surgery, The First Hospital, China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China; 2Department of Head and Neck Surgery, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People’s Republic of China; 3Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhang, Email jianzhang@cmu.edu.cnBackground: Long non-coding RNAs (lncRNAs) associated with immunogenic cell death (ICD) play a pivotal role in tumorigenesis and offer prognostic insights for papillary thyroid carcinoma (PTC) patients. This study delves into the impact of ICD-related lncRNAs on the prognosis of PTC.Methods: PTC samples were accessed from The Cancer Genome Atlas-Thyroid carcinoma database (TCGA-THCA) and consensus cluster analysis to elucidate the influence of ICD-related lncRNA expression. To gauge the prognostic significance of these lncRNAs, we developed a prognostic model. Additionally, we conducted GO and KEGG enrichment analyses, assessed immune cell infiltration (ICI) using CIBERSORT and ssGSEA, examined immune checkpoint expression, tumor mutation burden (TMB), tumor microenvironment (TME), T-cell dysfunction and exclusion (TIDE), TCIA, and drug sensitivity across various groups. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of LINC00924 in two PTC cell lines, BCPAP and TPC1, transfected with LINC00924 overexpression plasmids.Results: Two distinct clusters demonstrated varying TME, BRAF, NRAS, and ICI characteristics, suggesting potential immune mechanisms in PTC. Our prognostic model identified seven lncRNAs: SRRM2-AS1, AC008556.1, BHLHE40-AS1, EGOT, AL39066.1, LINC00924, and PICART1. The expression of ICD-related lncRNAs correlated with progression-free interval (PFI) in PTC patients. Overexpression of LINC00924 significantly reduced cell proliferation, migration, and invasion, while augmenting apoptosis in PTC cells.Conclusion: Our findings highlight the potential of ICD-related lncRNAs as prognostic biomarkers for PFI in PTC. In vitro experiments suggest a protective role of LINC00924 in PTC progression.Keywords: immunogenic cell death, LncRNA, papillary thyroid carcinoma, prognosis