Single-Cell RNA Sequencing and Systems Biology Analysis Reveal Cellular Heterogeneity and Immunotherapeutic Targets in Papillary Thyroid Cancer

Thyroidtumors (TC) are the most common endocrine cancer, accounting for ۹۰% of allendocrine neoplasms (۱).Thyroid cancer will be the fourth most common cancer in the United States by۲۰۳۰, after lung, liver, and pancreatic cancers (۲).Histological classification indicates that papillary thyroid carcinoma (PTC) isa differentiated thyroid cancer that originates from the thyroid's follicularcell epithelium (۳).It accounts for ۸۰–۸۵% of all instances, making it the most common category ofTC (۴).This study uses a dual method, single-cell analysis, and system biologyanalysis in response to the growing need for efficient treatments for papillarythyroid cancer. Through investigating the complexities of tumor heterogeneityand investigating possible targets for immunotherapy, the study seeks to openup new options for more accurate and focused treatments in the context ofpapillary thyroid cancer. This bioinformatics study aims to investigate thedifference in cell population in papillary thyroid cancer and normal thyroidcells, and their gene markers.Material and Methods:R language was used for analyzing the scRNA-seq data (GSE۱۹۳۵۸۱, GSE۱۵۸۲۹۱ and GSE۲۳۲۲۳۷) using the Seurat (۵), Celldex and SingleCellExperiment packages (۶, ۷). ۷۱۸۲۳ cells from ۱۶ samples including:۱۰ papillary thyroid cancer and ۶ normal. To evaluate dimensionality reductionand cell clustering, PCA and t-SNE were performed. To identify different celltypes and automated cluster annotation singleR package was used. Next analysespertaining to the biological system were conductedResults:Compared to normal tissue, DLGAP۵ was highly expressed in papillarythyroid cancer compared with normal thyroid cancer. Systems biology studies have alsodemonstrated that this gene exhibits elevated expression in papillary thyroidcancer, indicating its potential as both a diagnostic and therapeuticbiomarker.Conclusion:Possible immune-related biomarkershave been found through an analysis of the connection between the papillarythyroid and the immune system. These results can be used to establish clinically usefuldiagnostic and treatment strategies for papillary thyroid carcinoma.References: ۱. Crnčić TB, Tomaš MI, Girotto N, Ivanković SG. Risk factors for thyroid cancer: what do we know so far? Acta Clinica Croatica. ۲۰۲۰;۵۹(Suppl ۱):۶۶. ۲. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to ۲۰۳۰: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer research. ۲۰۱۴;۷۴(۱۱):۲۹۱۳-۲۱. ۳. Du Z, Wang B, Tan F, Wu Y, Chen J, Zhao F, et al. The regulatory role of LncRNA HCG۱۸ in various cancers. Journal of Molecular Medicine. ۲۰۲۳;۱۰۱(۴):۳۵۱-۶۰. ۴. Siegel RL, Miller KD, Jemal A. Cancer statistics, ۲۰۱۸. CA: a cancer journal for clinicians. ۲۰۱۸;۶۸(۱):۷-۳۰. ۵. Hao Y, Hao S, Andersen-Nissen E, Mauck WM, Zheng S, Butler A, et al. Integrated analysis of multimodal single-cell data. Cell. ۲۰۲۱;۱۸۴(۱۳):۳۵۷۳-۸۷. e۲۹. ۶. Aran D, Looney AP, Liu L, Wu E, Fong V, Hsu A, et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nature immunology. ۲۰۱۹;۲۰(۲):۱۶۳-۷۲.

کلیدواژه ها:

thyroid cancer ، Papillary thyroid cancer ، Single-Cell RNA-seq ، NGS ، Computational Biology