Integrated analysis of bulk and single cell datasets with experimental validation of cancer stemness function in thyroid cancer prognosis and immunotherapy

Cancer stem cells (CSCs) are vital in tumor development, immune therapy resistance, and thyroid carcinoma (THCA) advancement. Nonetheless, the exact mechanisms are still unclear. In this study, 28 mRNAs linked to cancer stemness were identified through an analysis of 13 publicly available THCA transcriptomic datasets alongside a CRISPR dataset for thyroid cancer cell lines. Importantly, we found a negative association between cancer stemness and the effectiveness of immunotherapy. By applying multiple machine learning techniques, a tumor stemness cell (TSC) model was both developed and validated, encompassing genes related to cancer stemness. This model effectively predicted patient prognosis and immunotherapy results for Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) immune checkpoint inhibitors (ICIs) treatment across various cancer types. Additionally, chromosomal amplifications in regions 1q and 8p were identified as intrinsic contributors to the onset of thyroid cancer. Specifically, based on single cell dataset, the amplification of CKS1B on chromosome 1q was revealed to advance the progression of thyroid cancer cells by boosting their proliferation. Moreover, experiments uncovered that the over-expression of CKS1B also significantly promoted the proliferation and invasion abilities of THCA, which maybe a potential therapeutic target for THCA. In conclusion, our research illuminates the correlation between cancer stem cell characteristics and the effectiveness of immunotherapy, offering a new framework for forecasting the outlook and response to immunotherapy in THCA patients on an individual basis.