NT5DC2 knockdown suppresses progression, glycolysis, and neuropathic pain in triple-negative breast cancer by blocking the EGFR pathway.

Triple-negative breast cancer (TNBC) is an exceptionally aggressive breast cancer subtype associated with neuropathic pain. This study explores the effects of 5'-nucleotidase domain-containing protein 2 (NT5DC2) on the progression of TNBC and neuropathic pain. Microarray analysis was conducted to identify differentially expressed genes in TNBC and the pathways involved. Gain- and loss-of-function assays of NT5DC2 were performed in TNBC cells, followed by detection of the extracellular acidification rate, adenosine triphosphate (ATP) levels, lactic acid production, glucose uptake, proliferation, migration, and invasion in TNBC cells. Macrophages were co-cultured with TNBC cells to examine the release of polarization-related factors and cytokines. A xenograft tumor model was established for in vivo validation. In addition, a mouse model of neuropathic pain was established through subepineural injection of TNBC cells, followed by measurement of the sciatic functional index and behavioral analysis to assess neuropathic pain. NT5DC2 was upregulated in TNBC and was positively correlated with epidermal growth factor receptor (EGFR). NT5DC2 interacted with EGFR to promote downstream signal transduction in TNBC cells. NT5DC2 knockdown diminished proliferation, migration, invasion, the extracellular acidification rate, ATP levels, lactic acid production, and glucose uptake in TNBC cells. Co-culture with NT5DC2-knockdown TNBC cells alleviated the M2 polarization of macrophages. Furthermore, NT5DC2 knockdown reduced tumor growth and neuropathic pain in mice. Importantly, activation of the EGFR pathway counteracted the effects of NT5DC2 knockdown. NT5DC2 knockdown protected against TNBC progression and neuropathic pain by inactivating the EGFR pathway.

The Value of Chinese Thyroid Imaging Report and Data System Combined With Contrast-Enhanced Ultrasound Scoring in Differential Diagnosis of Benign and Malignant Thyroid Nodules.

OBJECTIVES: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for differentiation of benign and malignant thyroid nodules. METHODS: A retrospective analysis of the conventional ultrasound and CEUS data of 388 nodules in 355 patients who had undergone thyroid nodule resection was conducted. All nodules had clear pathological results. The CEUS observation indexes included the enhancement degree in the arterial phase (no enhancement, scant punctate-linear enhancement, mild enhancement, moderate enhancement, and high enhancement) and wash-out patterns (rapid wash-out, slow wash-out, and isochronous wash-out). Chi-square test between groups and receiver operating characteristic curves (ROC) were used to determine the malignant (+1 point) and benign (-1 point) observation indexes that were statistically significant for the differentiation between benign and malignant thyroid nodules. The CEUS and C-TIRADS malignant and benign indexes were combined to score and draw the ROC curve, which was compared with the ROC curve scored by C-TIRADS alone to compare the diagnostic efficacy of the two methods for differentiating between benign and malignant thyroid nodules. RESULTS: Among the CEUS observation indexes, mild enhancement and rapid wash-out were malignant indexes, while isochronous wash-out was a benign index. The best diagnostic cut-off value for the differentiation of benign and malignant thyroid nodules using the C-TIRADS score and the C-TIRADS and CEUS combined score (C-TIRADS + CEUS score) was 2. The sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the two methods were 79.97, 75.48, 82.9, 70.5%, and 89.7, 72.9, 83.3, 82.5%, respectively. The area under the curve values were 0.840 and 0.877 (P < .001), respectively. CONCLUSIONS: The CEUS feature of mild enhancement in the arterial phase and rapid wash-out pattern are suggestive of malignancy and isochronous wash-out pattern is suggestive of benignity. The C-TIRADS + CEUS score has a higher value for distinguishing benign from malignant thyroid nodules than the C-TIRADS score alone.

Value of Contrast-Enhanced Ultrasound in Adjusting the Classification of Chinese-TIRADS 4 Nodules.

OBJECTIVES: To explore the value of applying contrast-enhanced ultrasound (CEUS) in adjusting the classification of category 4 nodules in the Chinese-Thyroid Imaging Report and Data System (C-TIRADS). METHODS: The data of preoperative conventional ultrasound and CEUS examinations of 125 C-TIRADS 4 nodules in 109 patients were retrospectively analyzed. We divided the thyroid nodules into two groups based on whether recommend by the guide fine-needle aspiration (FNA). Group I included C-TIRADS 4A nodules with a maximum diameter ≤15 mm and C-TIRADS 4B and 4C nodules with a maximum diameter ≤10 mm, and Group II included C-TIRADS 4A nodules with a maximum diameter >15 mm and C-TIRADS 4B and 4C nodules with a maximum diameter >10 mm. In CEUS, thyroid nodules showing suspicious malignant features such as hypoenhancement or early washout were adjusted to a level higher in the C-TIRADS classification; thyroid nodules showing possible benign features such as iso- or hyperenhancement were adjusted to a level lower; and thyroid nodules showing no enhancement were adjusted to C-TIRADS 3. Taking the pathological results as the gold standard, the receiver operating characteristic (ROC) curves of the C-TIRADS classification before and after the adjustment based on CEUS were plotted, and the diagnostic efficiency was compared. RESULTS: The sensitivity, specificity, accuracy, and positive and negative predictive values of the C-TIRADS classification for the diagnosis of thyroid nodule malignancy before the adjustment based on the CEUS results were 83.6%, 63.8%, 74.4%, 72.7%, and 77.1%, respectively, and these values were 91.0%, 82.8%, 87.2%, 85.9%, and 88.9%, respectively, after the adjustment. The area under the ROC curve (AUC) was 0.737 and 0.869, respectively, showing a significant difference (Z = 3.288, P=0.001). The diagnostic efficiency of C-TIRADS classification after the adjustment based on the CEUS results in both groups was improved compared with the result before the adjustment, and the difference in Group II was significant (Z = 2.931, P=0.003). CONCLUSIONS: CEUS significantly improved the diagnostic performance in the adjustment of C-TIRADS 4 nodule classification, especially for the nodules which needs FNA recommended by the C-TIRADS.