LINC01140 Hinders the Development of Breast Cancer Through Targeting miR-200b-3p to Downregulate DMD.

Long non-coding RNAs (lncRNAs) are frequently reported to be involved in breast cancer (BC) oncogenicity. The goal of this study was to probe lncRNA LINC01140's role and action mechanism in BC. Relative LINC01140, miR-200b-3p, and dystrophin (DMD) levels were determined using quantitative real-time polymerase chain reaction (qRT-PCR). DMD protein levels in BC cells were quantified using Western blotting, and the targeting relationships were validated by luciferase reporter assays and RNA immunoprecipitation experiments. The proliferative potential of the cells was evaluated using CCK-8 and colony formation tests, while the migratory and invasive abilities of the cells were assessed using scratch and transwell assays. Apoptosis was assessed by flow cytometry. Nude mouse models have been established to allow the examination of tumor growth in vivo. Pronounced downregulation of LINC01140 and DMD, as well as upregulation of miR-200b-3p, was observed in BC. LINC01140 binds directly to miR-200b-3p to downregulate DMD expression. Ectopic LINC01140 expression not only limited tumor growth in vivo but also diminished the proliferation, migration, and invasion abilities of BC cells in vitro, however, it induced apoptosis in BC cells. Elevated miR-200b-3p expression stimulated the tumorigenic potential of BC cells and attenuated the suppressive effect of LINC01140 or DMD overexpression on BC cell malignancy, whereas DMD overexpression restricted the tumorigenic potential of BC cells. Overall, LINC01140 prevents BC development via the miR-200b-3p-DMD axis. These findings support the latent potential and usefulness of the LINC01140-miR-200b-3p-DMD network as a target for BC therapy.

Aberrant kinesin family member 2A signifies tumor size and invasion, and may help predict prognosis of patients with papillary thyroid carcinoma.

Kinesin family member 2A (KIF2A) has been reported as an oncogene and potential biomarker for the progression of numerous cancer types; however, its role in papillary thyroid carcinoma (PTC) has remained elusive. The present study aimed to assess KIF2A expression in patients with PTC and explore the potential association between KIF2A, clinicopathological features and the prognosis of PTC. A total of 200 patients with PTC who received surgical resection were retrospectively reviewed. KIF2A expression was detected using immunohistochemistry (IHC) in 200 pairs of carcinoma/para-carcinoma tissues and using reverse transcription-quantitative PCR in 91 pairs of carcinoma/para-carcinoma tissues. Clinical and pathological data, disease-free survival (DFS) and overall survival (OS) rates of all patients were obtained. The results of the present study demonstrated that KIF2A protein and mRNA expression were both elevated in carcinoma tissues compared with those in para-carcinoma tissues. KIF2A protein expression in carcinoma tissues was positively associated with increased tumor size and a higher pathologic tumor-nodes-metastasis (pTNM) stage. However, KIF2A mRNA expression in carcinoma tissues was only associated with an increased pTNM stage and not with any other clinicopathological features. In addition, high levels of KIF2A protein expression in carcinoma tissues led to a poor predicted DFS, but were not associated with OS. Following adjustments using a multivariate Cox regression model, high KIF2A protein expression levels were indicated to be independently associated with a decreased DFS. In conclusion, aberrant KIF2A signifies tumor size and invasion, and may help to predict prognosis in patients with PTC.

Development and multicenter validation of a CT-based radiomics signature for predicting severe COVID-19 pneumonia.

OBJECTIVES: To develop and validate a radiomics nomogram for timely predicting severe COVID-19 pneumonia. MATERIALS AND METHODS: Three hundred and sixteen COVID-19 patients (246 non-severe and 70 severe) were retrospectively collected from two institutions and allocated to training, validation, and testing cohorts. Radiomics features were extracted from chest CT images. Radiomics signature was constructed based on reproducible features using the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm with 5-fold cross-validation. Logistic regression modeling was employed to build different models based on quantitative CT features, radiomics signature, clinical factors, and/or the former combined features. Nomogram performance for severe COVID-19 prediction was assessed with respect to calibration, discrimination, and clinical usefulness. RESULTS: Sixteen selected features were used to build the radiomics signature. The CT-based radiomics model showed good calibration and discrimination in the training cohort (AUC, 0.9; 95% CI, 0.843-0.942), the validation cohort (AUC, 0.878; 95% CI, 0.796-0.958), and the testing cohort (AUC, 0.842; 95% CI, 0.761-0.922). The CT-based radiomics model showed better discrimination capability (all p < 0.05) compared with the clinical factors joint quantitative CT model (AUC, 0.781; 95% CI, 0.708-0.843) in the training cohort, the validation cohort (AUC, 0.814; 95% CI, 0.703-0.897), and the testing cohort (AUC, 0.696; 95% CI, 0.581-0.796). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics model outperformed the clinical factors model and quantitative CT model alone. CONCLUSIONS: The CT-based radiomics signature shows favorable predictive efficacy for severe COVID-19, which might assist clinicians in tailoring precise therapy. KEY POINTS: • Radiomics can be applied in CT images of COVID-19 and radiomics signature was an independent predictor of severe COVID-19. • CT-based radiomics model can predict severe COVID-19 with satisfactory accuracy compared with subjective CT findings and clinical factors. • Radiomics nomogram integrated with the radiomics signature, subjective CT findings, and clinical factors can achieve better severity prediction with improved diagnostic performance.

CD8+ cytotoxic and FoxP3+ regulatory T lymphocytes serve as prognostic factors in breast cancer.

BACKGROUND: There is conflicting evidence regarding the prognostic value of cytotoxic T cell infiltration in breast cancer. The aims of this study were to detect the expression levels and localization of FoxP3 and CD8 in invasive ductal carcinoma of the breast and to investigate the correlations among FoxP3+ regulatory T cells (Tregs), CD8+ cytotoxic T lymphocytes (CTLs), clinicopathological features, and prognosis in patients with breast cancer. METHODS: Immunohistochemistry was used to detect the expression levels and localization of FoxP3 and CD8. One-sample t-test, one-way analysis of variance, and Kaplan-Meier log-rank tests were used to analyze correlations between the expression levels of CD8 and FoxP3; Kaplan-Meier Log-rank test was used to analyze clinicopathological features to explore the prognostic significance of CD8 and FoxP3 in patients with breast cancer. RESULTS: FoxP3 expression in the tumor bed was higher than that in the stroma, while CD8 was primarily expressed in the stroma. CD8 expression was associated with favorable prognostic factors. However, FoxP3 expression and an increased ratio of total FoxP3+ Tregs to CD8+ CTLs were significantly correlated with unfavorable prognostic factors. Additionally, an increased ratio was associated with molecular subtypes (ER+Her2+, ER+Her2-, ER-Her2+, and ER-Her2-) of breast cancer. Overexpression of FoxP3 and a high FoxP3+/CD8+ ratio were correlated with poor overall survival (OS) and disease-free survival (DFS). However, CD8 expression only affected OS in patients with breast cancer. CONCLUSIONS: Tumor-infiltrating lymphocytes are localized variously depending on the subtype. CD8+ CTLs were associated with a good prognosis, while FoxP3+ Tregs were associated with adverse outcomes in patients with breast cancer. CD8+ CTLs and FoxP3+ Tregs are potential predictive prognostic factors for patients with breast cancer.

Can a subgroup at high risk for LRR be identified from T1-2 breast cancer with negative lymph nodes after mastectomy? A meta-analysis.

Purpose: To identify a subgroup at high risk for loco-regional recurrence (LRR) from T1-2 breast cancer with negative lymph nodes (N0) after mastectomy by using a meta-analysis.Methods and materials: Published studies on the relationship between clinical features and LRR of breast cancer were identified from public databases, including PubMed, EMBASE, and the Cochrane Library. High-risk features for LRR in this patient population were defined based on the pooled results of meta-analysis.Results: For the meta-analysis, a total of 11244 breast cancers with pT1-2N0 after mastectomy from 20 publications were included for analysis. The pooled results indicated that age (hazard ratio (HR) 1.77, P=0.001), lymphovascular invasion (LVI) (HR 2.23, P<0.001), histologic grade (HR 1.66, P<0.001), HER2 status (HR 1.65, P=0.027), menopausal status (HR 1.36, P=0.015), and surgical margins (HR 2.56, P=0.014) were associated with a significantly increased risk of developing LRR in this patient population group, but not for tumor size (HR 1.32, P=0.23), systematic therapy (HR 1.67, P=0.20), and hormonal receptor status (HR 1.04, P=0.73).Conclusion: In the current study, patients with young age, positive LVI, high histologic grade, HER-2 positive, premenopausal, and positive surgical margins have an increased risk of developing LRR. Further prospective trials are needed to clearly define the role of adjuvant postmastectomy radiotherapy in T1-2N0 breast cancer at high risk of developing LRR.

Quantitative Aortic Distensibility Measurement Using CT in Patients with Abdominal Aortic Aneurysm: Reproducibility and Clinical Relevance.

Purpose. To investigate the reproducibility of aortic distensibility (D) measurement using CT and assess its clinical relevance in patients with infrarenal abdominal aortic aneurysm (AAA). Methods. 54 patients with infrarenal abdominal aortic aneurysm were studied to determine their distensibility by using 64-MDCT. Aortic cross-sectional area changes were determined at two positions of the aorta, immediately below the lowest renal artery (level 1.) and at the level of its maximal diameter (level 2.) by semiautomatic segmentation. Measurement reproducibility was assessed using intraclass correlation coefficient (ICC) and Bland-Altman analyses. Stepwise multiple regression analysis was performed to assess linear associations between aortic D and anthropometric and biochemical parameters. Results. A mean distensibility of Dlevel 1. = (1.05 ± 0.22) × 10-5 Pa-1 and Dlevel 2. = (0.49 ± 0.18) × 10-5 Pa-1 was found. ICC proved excellent consistency between readers over two locations: 0.92 for intraobserver and 0.89 for interobserver difference in level 1. and 0.85 and 0.79 in level 2. Multivariate analysis of all these variables showed sac distensibility to be independently related (R2 = 0.68) to BMI, diastolic blood pressure, and AAA diameter. Conclusions. Aortic distensibility measurement in patients with AAA demonstrated high inter- and intraobserver agreement and may be valuable when choosing the optimal dimensions graft for AAA before endovascular aneurysm repair.

Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells.

EZH2, the catalytic subunit of polycomb repressor complex 2, has oncogenic properties, whereas RASSF2A, a Ras association domain family protein, has a tumor suppressor role in many types of human cancer. However, the interrelationship between these two genes remains unclear. Here, we showed that the downregulation of EZH2 reduces CpG island methylation of the RASSF2A promoter, thereby leading to increased RASSF2A expression. Our findings also showed that knockdown of EZH2 increased RASSF2A expression in the human breast cancer cell line MCF-7 in cooperation with DNMT1. This was similar to the effect of 5-Aza-CdR, a DNA methylation inhibitor that reactivates tumor suppressor genes and activated RASSF2A expression in our study. The EZH2 inhibitor DZNep markedly suppressed the proliferation, migration, and invasion of MCF-7 cells treated with ADR and TAM. EZH2 inhibits the expression of tumor suppressor gene RASSF2A via promoter hypermethylation. Thus, it plays an important role in tumorigenesis and is a potential therapeutic target for the treatment of breast cancer.

Effects of Notch-1 down-regulation on malignant behaviors of breast cancer stem cells.

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.