A Pan-Cancer Analysis to Provide Insight into the Immunological Role and Prognostic Value of HTRA3.

High-temperature requirement factor A3 (HTRA3), a member of the HTRA protein family, is closely associated with apoptosis and plays a crucial role in controlling signal transmission and cancer development. However, the regulatory pathways of HTRA3 in tumors are not fully understood, necessitating a comprehensive analysis of HTRA3 in cancers. In this study, we conducted a multi-omics analysis of HTRA3 in pan-cancer using data from various databases including TCGA, cBioPortal, GeneMANIA, DAVID, TIMER2.0, SangerBox, and RNAactDrug. Our analysis included gene expression, survival prognosis, diagnostic value, mutation, gene-gene interaction, enrichment analysis, and drug sensitivity analysis. We found that HTRA3 is aberrantly expressed in a variety of cancers and significantly correlates with diagnosis, prognosis, TMB, MSI, immune checkpoint (ICP) genes, and drug sensitivity in various cancer types. HTRA3 is involved in a variety of cancer pathways, particularly extracellular matrix (ECM) alterations, and has a potential role in epithelial-mesenchymal transition (EMT). HTRA3 expression is positively correlated with the abundance of cancer-associated fibroblasts (CAFs) and endothelial cells in the tumor microenvironment, and is also positively correlated with immune scores, stromal scores, and ESTIMATE scores in multiple cancers. HTRA3 is often overexpressed in cancer and is associated with poor prognosis and regulation of the tumor's immune response. Therefore, it may serve as a novel biomarker for tumor diagnosis and treatment.

The effectiveness of ultrasound-guided core needle biopsy in detecting lymph node metastases in the axilla in patients with breast cancer: systematic review and meta-analysis.

OBJECTIVE: This study aimed to perform a meta-analysis to investigate the diagnostic safety and accuracy of Ultrasound-Guided Core Needle Biopsy (US-CNB) Axillary Lymph Nodes (ALNs) region in patients with Breast Cancer (BC). METHODS: The authors searched the electronic databases PubMed, Scopus, Embase, and Web of Science for clinical trials about US-CNB for the detection of ALNs in breast cancer patients. The authors extracted and pooled raw data from the included studies and performed statistical analyses using Meta-DiSc 1.4 and Review Manager 5.3 software. A random effects model was used to calculate the data. At the same time, data from the Ultrasound-guided Fine-Needle Aspiration (US-FNA) were introduced for comparison with the US-CNB. In addition, the subgroup was performed to explore the causes of heterogeneity. (PROSPERO ID: CRD42022369491). RESULTS: In total, 18 articles with 2521 patients were assessed as meeting the study criteria. The overall sensitivity was 0.90 (95% CI [Confidence Interval], 0.87‒0.91; p = 0.00), the overall specificity was 0.99 (95% CI 0.98‒1.00; p = 0.62), the overall area under the curve (AUC) was 0.98. Next, in the comparison of US-CNB and US-FNA, US-CNB is better than US-FNA in the diagnosis of ALNs metastases. The sensitivity was 0.88 (95% CI 0.84‒0.91; p = 0.12) vs. 0.73 (95% CI 0.69‒0.76; p = 0.91), the specificity was 1.00 (95% CI 0.99‒1.00; p = 1.00) vs. 0.99 (95% CI 0.67‒0.74; p = 0.92), and the AUC was 0.99 vs. 0.98. Subgroup analysis showed that heterogeneity may be related to preoperative Neoadjuvant Chemotherapy (NAC) treatment, region, size of tumor diameter, and the number of punctures. CONCLUSION: US-CNB has a satisfactory diagnostic performance with good specificity and sensitivity in the preoperative diagnosis of ALNs in BC patients.

Dynamin-2 regulates microtubule stability via an endocytosis-independent mechanism.

Microtubule stability and dynamics regulations are essential for vital cellular processes, such as microtubule-dependent axonal transport. Dynamin is involved in many membrane fission events, such as clathrin-mediated endocytosis. The ubiquitously expressed dynamin-2 has been reported to regulate microtubule stability. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the roles of intrinsic properties of dynamin-2 on microtubule regulation by rescue experiments. A heterozygous DNM2 mutation in HeLa cells was generated, and an increase in the level of stabilized microtubules in these heterozygous cells was observed. The expression of wild-type dynamin-2 in heterozygous cells reduced stabilized microtubules. Conversely, the expression of self-assembly-defective mutants of dynamin-2 in the heterozygous cells failed to decrease stabilized microtubules. This indicated that the self-assembling ability of dynamin-2 is necessary for regulating microtubule stability. Moreover, the heterozygous cells expressing the GTPase-defective dynamin-2 mutant, K44A, reduced microtubule stabilization, similar to the cells expressing wild-type dynamin-2, suggesting that GTPase activity of dynamin-2 is not essential for regulating microtubule stability. These results showed that the mechanism of microtubule regulation by dynamin-2 is diverse from that of endocytosis.

The effectiveness of ultrasound-guided core needle biopsy in detecting lymph node metastases in the axilla in patients with breast cancer: systematic review and meta-analysis

Abstract Objective: This study aimed to perform a meta-analysis to investigate the diagnostic safety and accuracy of Ultrasound-Guided Core Needle Biopsy (US-CNB) Axillary Lymph Nodes (ALNs) region in patients with Breast Cancer (BC). Methods: The authors searched the electronic databases PubMed, Scopus, Embase, and Web of Science for clinical trials about US-CNB for the detection of ALNs in breast cancer patients. The authors extracted and pooled raw data from the included studies and performed statistical analyses using Meta-DiSc 1.4 and Review Manager 5.3 software. A random effects model was used to calculate the data. At the same time, data from the Ultrasound-guided Fine-Needle Aspiration (US-FNA) were introduced for comparison with the US-CNB. In addition, the subgroup was performed to explore the causes of heterogeneity. (PROSPERO ID: CRD42022369491). Results: In total, 18 articles with 2521 patients were assessed as meeting the study criteria. The overall sensitivity was 0.90 (95% CI [Confidence Interval], 0.87‒0.91; p = 0.00), the overall specificity was 0.99 (95% CI 0.98‒ 1.00; p = 0.62), the overall area under the curve (AUC) was 0.98. Next, in the comparison of US-CNB and US-FNA, US-CNB is better than US-FNA in the diagnosis of ALNs metastases. The sensitivity was 0.88 (95% CI 0.84‒ 0.91; p = 0.12) vs. 0.73 (95% CI 0.69‒0.76; p = 0.91), the specificity was 1.00 (95% CI 0.99‒1.00; p = 1.00) vs. 0.99 (95% CI 0.67‒0.74; p = 0.92), and the AUC was 0.99 vs. 0.98. Subgroup analysis showed that heterogeneity may be related to preoperative Neoadjuvant Chemotherapy (NAC) treatment, region, size of tumor diameter, and the number of punctures. Conclusion: US-CNB has a satisfactory diagnostic performance with good specificity and sensitivity in the preoperative diagnosis of ALNs in BC patients.