甲狀腺癌（THCA）的死亡率增加，這是最常見的內分泌惡性腫瘤。通過分析23個THCA腫瘤樣本的單細胞RNA测序（Sc-RNAseq）數據，我們確定了THAC微環境中的六種不同細胞類型，表明局部腫瘤多樣性高。通過對免疫亞群細胞、髓樣細胞、癌相關成纖維細胞和甲狀腺細胞亞集進行重新分類，我們深入揭示了甲狀腺癌的腫瘤微環境差異。通過對甲狀腺細胞亞集的深入分析，我們確定了甲狀腺細胞退化的過程（正常、中間、惡性細胞）。通過細胞間通信分析，我們發現甲狀腺細胞與成纖維細胞和B細胞在MIF信號通路上有著強烈的聯繫。此外，我們還發現甲狀腺細胞與B細胞、TampNK細胞和骨髓細胞之間存在著強烈的相關性。最後，我們基於從單細胞分析中不同ially基因表達開發了一個預後模型。在訓練集和測試集中，它能夠有效預測甲狀腺癌患者的生存。此外，我們發現高風險和低風險患者的免疫亞群細胞組成存在顯著差異，這可能是其不同預後的原因。通過體外實驗，我們確定NPC2的沉默可以顯著促進甲狀腺癌細胞的凋亡，而NPC2可能是甲狀腺癌的潛在治療靶點。在本研究中，我們基於Sc-RNAseq數據開發了一個良好的預後模型，揭示了甲狀腺癌的細胞微環境和腫瘤多樣性。這將有助於在臨床診斷中為患者提供更準確的個性化治療。© 2023作者（S），在Springer-Verlag GmbH Germany的專屬許可下，屬於Springer Nature的一部分。

There has been an increase in the mortality rate of thyroid cancer (THCA), which is the most common endocrine malignancy. We identified six distinct cell types in the THAC microenvironment by analyzing single-cell RNA sequencing (Sc-RNAseq) data from 23 THCA tumor samples, indicating high intratumoral heterogeneity. Through re-dimensional clustering of immune subset cells, myeloid cells, cancer-associated fibroblasts, and thyroid cell subsets, we deeply reveal differences in the tumor microenvironment of thyroid cancer. Through an in-depth analysis of thyroid cell subsets, we identified the process of thyroid cell deterioration (normal, intermediate, malignant cells). Through cell-to-cell communication analysis, we found a strong link between thyroid cells and fibroblasts and B cells in the MIF signaling pathway. In addition, we found a strong correlation between thyroid cells and B cells, TampNK cells, and bone marrow cells. Finally, we developed a prognostic model based on differentially expressed genes in thyroid cells from single-cell analysis. Both in the training set and the testing set, it can effectively predict the survival of thyroid patients. In addition, we identified significant differences in the composition of immune cell subsets between high-risk and low-risk patients, which may be responsible for their different prognosis. Through in vitro experiments, we identify that knockdown of NPC2 can significantly promote thyroid cancer cell apoptosis, and NPC2 may be a potential therapeutic target for thyroid cancer. In this study, we developed a well-performing prognostic model based on Sc-RNAseq data, revealing the cellular microenvironment and tumor heterogeneity of thyroid cancer. This will help to provide more accurate personalized treatment for patients in clinical diagnosis.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.