Abstract
Background Early cervical lymph node (LN) metastasis is an important cause of poor survival in patients with medullary thyroid cancer (MTC). This study evaluated whether the preoperative serum calcitonin level in combination with ultrasonographic features of MTC can be used to assess the LN status as well as predict the risk of metastasis in patients with MTC. Methods We retrospectively analyzed the clinical data of 95 patients with MTC, and a nomogram model was constructed and validated. Using integrated database analysis of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), we mined pathways wherein CALCA is involved, identified calcitonin-related genes, and analyzed their functions. Results Correlation analysis revealed a significant association between the infiltrating range, diameter, calcification, blood flow, the preoperative serum calcitonin level, and metastasis. The metastasis risk-prediction model showed great accuracy in determining the risk of metastasis in MTC (area under the curve of the receiver operating characteristic [ROC] curve: 0.979 [95% confidence interval 0.946–1.000]). Decision curve analysis (DCA) showed that the model has excellent clinical utilization potential. Significantly, CALCA, the mRNA for calcitonin, was highly expressed in thyroid cancer tissues and associated with the cytokine–cytokine receptor and neuroactive ligand-receptor interaction pathways as well as the cell-adhesion molecules. ROC curve indicated that the CNTFR, CD27, GDF6, and TSLP genes, which are related to the cytokine–cytokine receptor interaction pathway, could indicate the risk of metastasis in MTC. Conclusions The preoperative serum calcitonin level, in combination with ultrasonographic features, can be used to predict the risk of metastasis in patients with MTC and constitute a noninvasive accurate method for preoperative diagnosis of MTC.
Highlights
Medullary thyroid carcinoma (MTC) is an undifferentiated malignant tumor that arises from the parafollicular cells of the thyroid (C cells) within the diffuse neuroendocrine cell system [1]
We developed a nomogram model to visualize the risk factors that are associated with the lymphatic metastasis of medullary thyroid cancer (MTC)
We emphasize the key role of preoperative serum calcitonin levels and ultrasonographic evaluation of MTC primary foci in the assessment of the patient’s risk of lymphatic metastasis to enable a risk-based selection of an appropriate surgical approach to achieve a good prognosis for the patient
Summary
Medullary thyroid carcinoma (MTC) is an undifferentiated malignant tumor that arises from the parafollicular cells of the thyroid (C cells) within the diffuse neuroendocrine cell system [1]. Cervical lymph node (LN) metastasis is an important cause of poor survival in patients with medullary thyroid cancer (MTC). This study evaluated whether the preoperative serum calcitonin level in combination with ultrasonographic features of MTC can be used to assess the LN status as well as predict the risk of metastasis in patients with MTC. CALCA, the mRNA for calcitonin, was highly expressed in thyroid cancer tissues and associated with the cytokine–cytokine receptor and neuroactive ligand-receptor interaction pathways as well as the cell-adhesion molecules. The preoperative serum calcitonin level, in combination with ultrasonographic features, can be used to predict the risk of metastasis in patients with MTC and constitute a noninvasive accurate method for preoperative diagnosis of MTC
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