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BACKGROUND: The reclassification of Papillary Thyroid Carcinoma (PTC) is an area of research that warrants attention. The connection between thyroid cancer, inflammation, and immune responses necessitates considering the mechanisms of differential prognosis of thyroid tumors from an immunological perspective. Given the high adaptability of macrophages to environmental stimuli, focusing on the differentiation characteristics of macrophages might offer a novel approach to address the issues related to PTC subtyping. METHODS: Single-cell RNA sequencing data of medullary cells infiltrated by papillary thyroid carcinoma obtained from public databases was subjected to dimensionality reduction clustering analysis. The RunUMAP and FindAllMarkers functions were utilized to identify the gene expression matrix of different clusters. Cell differentiation trajectory analysis was conducted using the Monocle R package. A complex regulatory network for the classification of Immune status and Macrophage differentiation-associated Papillary Thyroid Cancer Classification (IMPTCC) was constructed through quantitative multi-omics analysis. Immunohistochemistry (IHC) staining was utilized for pathological histology validation. RESULTS: Through the integration of single-cell RNA and bulk sequencing data combined with multi-omics analysis, we identified crucial transcription factors, immune cells/immune functions, and signaling pathways. Based on this, regulatory networks for three IMPTCC clusters were established. CONCLUSION: Based on the co-expression network analysis results, we identified three subtypes of IMPTCC: Immune-Suppressive Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (ISMPTCC), Immune-Neutral Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (INMPTCC), and Immune-Activated Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (IAMPTCC). Each subtype exhibits distinct metabolic, immune, and regulatory characteristics corresponding to different states of macrophage differentiation.
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OBJECTIVE: Distant metastasis of thyroid cancer often indicates poor prognosis, and it is important to identify patients who have developed distant metastasis or are at high risk as early as possible. This paper aimed to predict distant metastasis of thyroid cancer through the construction of machine learning models to provide a reference for clinical diagnosis and treatment. MATERIALS & METHODS: Data on demographic and clinicopathological characteristics of thyroid cancer patients between 2010 and 2015 were extracted from the National Institutes of Health (NIH) Surveillance, Epidemiology, and End Results (SEER) database. Our research used univariate and multivariate logistic models to screen independent risk factors, respectively. Decision Trees (DT), ElasticNet (ENET), Logistic Regression (LR), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Multilayer Perceptron (MLP), Radial Basis Function Support Vector Machine (RBFSVM) and seven machine learning models were compared and evaluated by the following metrics: the area under receiver operating characteristic curve (AUC), calibration curve, decision curve analysis (DCA), sensitivity(also called recall), specificity, precision, accuracy and F1 score. Interpretable machine learning was used to identify possible correlation between variables and distant metastasis. RESULTS: Independent risk factors for distant metastasis, including age, gender, race, marital status, histological type, capsular invasion, and number of lymph nodes metastases were screened by multifactorial regression analysis. Among the seven machine learning algorithms, RF was the best algorithm, with an AUC of 0.948, sensitivity of 0.919, accuracy of 0.845, and F1 score of 0.886 in the training set, and an AUC of 0.960, sensitivity of 0.929, accuracy of 0.906, and F1 score of 0.908 in the test set. CONCLUSIONS: The machine learning model constructed in this study helps in the early diagnosis of distant thyroid metastases and helps physicians to make better decisions and medical interventions.
