A comprehensive analysis to reveal the underlying molecular mechanisms of natural killer cell in thyroid carcinoma based on single-cell RNA sequencing data

Background: Thyroid carcinoma (THCA) is the most common cancer of the endocrine system. Natural killer (NK) cell play an important role in tumor immune surveillance. The aim of this study was to explore the possible molecular mechanisms involved in NK cell in THCA to help the management and treatment of the disease.

Methods: All data were downloaded from public databases. Candidate hub genes associated with NK cell in THCA were identified by limma, WGCNA and singleR packages. Functional enrichment analysis was performed on the candidate hub genes. Hub genes associated with NK cell were identified by Pearson correlation analysis. The mRNA-miRNA-lncRNA and transcription factors (TF) networks were constructed and the drug was predicted.

Results: The infiltration level of NK cell in THCA tissues was higher than that in paracancerous tissues. KEGG functional enrichment analysis only obtained two signaling pathways, thyroid hormone synthesis and mineral absorption. CTSC, FN1, SLC34A2 and TMSB4X identified by Pearson correlation analysis were considered as the hub genes. Receiver operating characteristic analysis suggested that hub genes may be potential diagnostic biomarkers. In mRNA-miRNA-lncRNA network, FN1 had the highest correlation with IQCH-AS1, and IQCH-AS1 was also correlated with hsa-miR-543. In addition, FN1 and RUNX1 were also found to have the highest correlation in TF network. Finally, NK cell-related drugs belinostat and vorinostat were identified based on ASGARD.

Conclusion: The identification of important signaling pathways, molecules and drugs provides potential research directions for further research in THCA and contributes to the development of diagnostic and therapeutic approaches for this disease.