Abstract
Although immunotherapy has recently demonstrated a substantial promise in treating advanced thyroid carcinoma (THCA), it is not appropriate for all THCA patients. As a result, this study aims to identify biomarkers for predicting immunotherapy efficacy and prognosis in THCA patients based on a constructed prognostic model. The transcriptomic and corresponding clinical data of THCA patients were obtained from the Cancer Genome Atlas (TCGA) database. We identified differentially expressed genes (DEGs) between THCA and normal samples and performed an intersection analysis of DEGs with immune-related genes (IRGs) downloaded from the ImmPort database. Functional enrichment analysis was performed on the chosen immune-related DEGs. Subsequently, Cox and LASSO regression analyses were conducted to obtain three hub immune-related DEGs, including PPBP, SEMA6B, and GCGR. Following that, a prognostic risk model was established and validated based on PPBP, SEMA6B, and GCGR genes to predict immunotherapy efficacy and THCA prognosis. Finally, we investigated the association between the constructed risk model and tumor mutational burden (TMB), abundance of tumor-infiltrating immune cells (TICs) as well as immunotherapeutic targets (PDL-1, PD-1, and CTLA4) in THCA. THCA patients in the high-risk score (RS) group showed higher TMB levels and worse prognosis than the low RS group. Patients in the high-RS group had higher proportions of monocytes, M2 macrophages, and activated dendritic cells, whereas those in the low-RS group exhibited higher numbers of M1 macrophages and dendritic resting cells. Our data implied that the constructed THCA prognostic model was sound and we concluded that the THCA patients having high TMB and low PD-L1 expression levels might respond poorly to immunotherapy. Taken together, we constructed a novel prognostic model for THCA patients to predict their prognosis and immunotherapy efficacy, providing a viable option for the future management of THCA patients in the clinic.
Highlights
Thyroid carcinoma (THCA) is the fifth most prevalent malignancy affecting women (Zhang et al, 2019b) and a major cause of annual endocrine malignancies death (Aboelnaga and Ahmed., 2015)
The results revealed that the relative abundance of monocytes, M2 macrophages, activated dendritic cells was significantly higher in high-risk score (RS) group than those in low-RS group (p 0.017, p 0.042 and p < 0.001, respectively), whereas M1 macrophages and dendritic resting cells in high-RS group exhibited lower relative abundance (p 0.036 and p 0.002, respectively)
The results revealed that the low-risk group significantly increased PD−L1 expression levels compared with the high-risk group (p 0.044, Figure 10A), implying that lowRS THCA patients might be more susceptible to immunotherapy
Summary
Thyroid carcinoma (THCA) is the fifth most prevalent malignancy affecting women (Zhang et al, 2019b) and a major cause of annual endocrine malignancies death (Aboelnaga and Ahmed., 2015). The incidence of THCA has been escalating worldwide (Cabanillas et al, 2016). Most THCA is welldifferentiated PTC with a 10-years survival rate of over 95%, some variants of PTC may demonstrate increased aggressive behavior, in older patients, contributing to significant mortality (Nath and Erickson., 2018). Surgical resection and radioiodine (RAI) therapy were considered standard treatments for most THCA patients. Survival rates for advanced thyroid cancer patients remain low. For these reasons, novel therapeutic strategies, such as immunotherapies and targeted molecular therapy, are under investigation for treating advanced or metastatic THCA patients
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