Radiogenomic Analysis of Papillary Thyroid Carcinoma for Prediction of Cervical Lymph Node Metastasis: A Preliminary Study

Abstract

BackgroundPapillary thyroid carcinoma (PTC) is characterized by frequent metastases to cervical lymph nodes (CLNs), and the presence of lymph node metastasis at diagnosis has a significant impact on the surgical approach. Therefore, we established a radiomic signature to predict the CLN status of PTC patients using preoperative thyroid ultrasound, and investigated the association between the radiomic features and underlying molecular characteristics of PTC tumors.MethodsIn total, 270 patients were enrolled in this prospective study, and radiomic features were extracted according to multiple guidelines. A radiomic signature was built with selected features in the training cohort and validated in the validation cohort. The total protein extracted from tumor samples was analyzed with LC/MS and iTRAQ technology. Gene modules acquired by clustering were chosen for their diagnostic significance. A radiogenomic map linking radiomic features to gene modules was constructed with the Spearman correlation matrix. Genes in modules related to metastasis were extracted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and a protein-protein interaction (PPI) network was built to identify the hub genes in the modules. Finally, the screened hub genes were validated by immunohistochemistry analysis.ResultsThe radiomic signature showed good performance for predicting CLN status in training and validation cohorts, with area under curve of 0.873 and 0.831 respectively. A radiogenomic map was created with nine significant correlations between radiomic features and gene modules, and two of them had higher correlation coefficient. Among these, MEmeganta representing the upregulation of telomere maintenance via telomerase and cell-cell adhesion was correlated with ‘Rectlike’ and ‘deviation ratio of tumor tissue and normal thyroid gland’ which reflect the margin and the internal echogenicity of the tumor, respectively. MEblue capturing cell-cell adhesion and glycolysis was associated with feature ‘minimum calcification area’ which measures the punctate calcification. The hub genes of the two modules were identified by protein-protein interaction network. Immunohistochemistry validated that LAMC1 and THBS1 were differently expressed in metastatic and non-metastatic tissues (p=0.003; p=0.002). And LAMC1 was associated with feature ‘Rectlike’ and ‘deviation ratio of tumor and normal thyroid gland’ (p<0.001; p<0.001); THBS1 was correlated with ‘minimum calcification area’ (p<0.001).ConclusionsThe radiomic signature proposed here has the potential to noninvasively predict the CLN status in PTC patients. Merging imaging phenotypes with genomic data could allow noninvasive identification of the molecular properties of PTC tumors, which might support clinical decision making and personalized management.

Ultrasound-based radiomics nomogram combined with clinical features for the prediction of central lymph node metastasis in papillary thyroid carcinoma patients with Hashimoto’s thyroiditis

“…The AUCs of the three models were 0.833, 0.731, and 0.711, respectively, which demonstrated that both the thyroid gland and thyroid nodules contributed to the identification of CLNM. This result was supported by Tong et al, who reported that the radiomics features of thyroid nodules can predict CLNM in patients with PTC (28). However, only a small number of patients with HT were included in this study.…”

Ultrasound-based radiomics analysis for preoperative prediction of central and lateral cervical lymph node metastasis in papillary thyroid carcinoma: a multi-institutional study

“…Besides, US examination is an empirical diagnosis which is greatly affected by the expertise of the operator; therefore, prone to interobserver variability when determining lateral LNM [ 8 ]. Many studies have investigated the association between cervical LNM and the morphologic US features of the primary tumor, and have reported that the “taller than wide” shape, tumor size, presence of calcification, and closer distance between tumor and capsule were independent risk factors for LNM [ 15 , 24 – 26 ]. Although the US features mentioned above are encouraging, the imaging features are also based on the judgment of the performing physician and thus, lack objectivity.…”

The efficacy and safety of microwave ablation versus conventional open surgery for the treatment of papillary thyroid microcarcinoma: a systematic review and meta-analysis

“…Ultrasound-guided microwave ablation (MWA) technology has achieved good safety and therapeutic effects in the treatment of benign thyroid nodules, and compared to OS, MWA technology results in fewer postoperative complications, has no effect on thyroid function, causes less trauma, and enables the faster recovery, and improved appearance of some PTMC patients (7)(8)(9). However, Tong's study mentioned that MWA only inactivates cancer nodules and does not remove the surrounding lymph nodes, and has a high risk of residual cancer foci and lymph node metastasis, even after microwave ablation, there are still a few tumors with recurrence and lymph node metastasis, which can not be used as a routine treatment for primary operable primary thyroid cancer (10). Therefore, MWA is a non-radical treatment for tumors, and its use as a routine treatment remains controversial (11).…”