Background: This study aimed to explore the risk factors of central lymph node metastasis (CLNM) in patients with clinical central lymph node-negative papillary thyroid carcinoma (PTC), and emphasize the guidance of the risk scoring model for prophylactic central lymph node dissection (pCLND) in patients with clinical lymph node-negative (cN0) PTC. Methods: A total of 582 patients with cN0 PTC who underwent unilateral/bilateral thyroidectomy and prophylactic central lymph node dissection (pCLND) in the Affiliated Hospital of Nantong University from January 2020 to February 2021 were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the risk factors of cN0 PTC. According to the independent risk factors of patients with cN0 PTC, a risk-scoring model was established. Then, the rationality of this risk scoring model was verified by additional clinical data of 112 patients with cN0 PTC in the Affiliated Hospital of Nantong University from March 2021 to April 2021.Results: Among 582 cases of cN0 PTC, 53.6% of the patients with cN0 had CLNM. The independent risk factors for CLNM in patients with cN0 PTC included male gender, <45 years of age, tumor with a maximum diameter of ≥1.0 cm, tumor location: middle/lower poles of the thyroid gland, multifocality, and extrathyroidal extension (ETE), and some ultrasound features, such as intra-nodular vascularity, microcalcification, irregular shape, and infiltrative margin. According to independent risk factors, a 24-point risk scoring model was established to predict CLNM in patients with cN0 PTC.Conclusions: Currently, prophylactic central neck lymph node dissection is a controversial operation, which should be selectively performed only for high-risk patients with cN0 PTC. For cN0 PTC patients with scores ≥14 and high-risk patients, even if no CLNM is found before surgery, routine prophylactic CLND is recommended. In addition, for cN0 PTC patients with a score of fewer than 14 points, it is recommended to perform fine-needle aspiration (FNA) before surgery, carefully assess the condition of the central lymph nodes, and then select the best surgical plan based on the results of the assessment.

BackgroundThyroid cancer (THCA) is the most prevalent malignant disease of the endocrine system, in which 5-year survival can attain about 95%, but patients with metastasis have a poor prognosis. Very little is known about the role of CAPN8 in the metastasis of THCA. In particular, the effect of CAPN8 on the tumor immune microenvironment (TIME) and immunotherapy response is unclear.Material and methodsMultiome datasets and multiple cohorts were acquired for analysis. Firstly, the expression and the prognostic value of CAPN8 were explored in public datasets and in vitro tumor tissues. Then, hierarchical clustering analysis was performed to identify the immune subtypes of THCA according to the expression of CAPN8 and the activities of related pathways. Subsequent analyses explored the different patterns of TIME, genetic alteration, DNA replication stress, drug sensitivity, and immunotherapy response among the three immune phenotypes. Finally, five individual cohorts of thyroid cancer were utilized to test the robustness and extrapolation of the three immune clusters.ResultsCAPN8 was found to be a significant risk factor for THCA with a markedly elevated level of mRNA and protein in tumor tissues. This potential oncogene could induce the activation of epithelial–mesenchymal transition and E2F-targeted pathways. Three subtypes were identified for THCA, including immune exhausted, inflamed, and immune desert phenotypes. The exhausted type was characterized by a markedly increased expression of inhibitory receptors and infiltration of immune cells but was much more likely to respond to immunotherapy. The immune desert type was resistant to common chemotherapeutics with extensive genomic mutation and copy number variance.ConclusionThe present study firstly explored the role of CAPN8 in the metastasis of THCA from the aspects of TIME. Three immune subtypes were identified with quite different patterns of prognosis, immunotherapy response, and drug sensitivity, providing novel insights for the treatment of THCA and helping understand the cross-talk between CAPN8 and tumor immune microenvironment.