Systematic review and meta-analysis of multiparametric MRI clear cell likelihood scores for classification of small renal masses.

Purpose: To systematically assess the multiparametric MRI clear cell likelihood score (ccLS) algorithm for the classification of small renal masses (SRM). Methods: We conducted an electronic literature search on Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar to identify relevant articles from 2017 up to June 30, 2022. We included studies reporting the diagnostic performance of the ccLS for characterization of solid SRM. The bivariate model and hierarchical summary receiver operating characteristic (HSROC) model were used to pool sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR). The quality evaluation was performed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: A total of 6 studies with 825 renal masses (785 patients) were included in the current meta-analysis. The pooled sensitivity and specificity for cT1a renal masses were 0.80 (95% CI 0.75-0.85) and 0.74 (95% CI 0.65-0.81) at the threshold of ccLS ≥4, the pooled LR+, LR-, and DOR were 3.04 (95% CI 2.34-3.95), 0.27 (95% CI 0.22-0.33), and 11.4 (95% CI 8.2-15.9), respectively. The area under the HSROC curve was 0.84 (95% CI 0.81-0.87). For all cT1 renal masses, the pooled sensitivity and specificity were 0.80 (95% CI 0.74-0.85) and 0.76 (95% CI 0.67-0.83). Conclusions: The ccLS had moderate to high accuracy for identifying ccRCC from other RCC subtypes and with a moderate inter-reader agreement. However, its diagnostic performance remain needs multi-center, large cohort studies to validate in the future.

Expression of GMFB in High-Grade Cervical Intraepithelial Neoplasia and Its Role in Cervical Cancer.

Cervical intraepithelial neoplasia (CIN) is a collective term for specific precancerous lesions associated with cervical cancer (CC). Although it has been affirmed with slow development of several levels of cellular changes, the existing poor prognosis calls for an urgent need to diagnose CIN at early stage and be aware of markers related to its pathogenesis and prognosis. We explored the expression level of a newly marker GMFB and its regulatory effect on CIN and CC. Patient samples and cell models were included. Bioinformatic studies were taken to predict its binding to miR-143-3p, miR-26b-5p, miR-191-5p, and miR-223-3p. Luciferase reporter and RNA pull-down assays were used to validate the prediction. Edu assay and flow cytometry were used to measure the regulation of GMFB on proliferation and apoptosis of CC cells. qRT-PCR was used for mRNA expression level detection. The results showed that GMFB was targeted by miR-143-3p, miR-26b-5p, miR-191-5p, and miR-223-3p. It had elevated expression in both CIN and CC samples. GMFB had highly prognostic value for CIN, and lymph node metastasis of CC was much associated with high GMFB expression level. Besides, silencing of GMFB inhibited CC cell proliferation and elevated cell apoptosis. In conclusion, we determined that GMFB has regulatory effect on high grade CIN and CC, which could lighten a novel way in exploring their pathogenesis and improving accuracy of prognosis.

Deficiency of Integrin ß4 Results in Increased Lung Tissue Stiffness and Responds to Substrate Stiffness via Modulating RhoA Activity.

The interaction between extracellular matrix (ECM) and epithelial cells plays a key role in lung development. Our studies found that mice with conditional integrin ß4 (ITGB4) knockout presented lung dysplasia and increased stiffness of lung tissues. In accordance with our previous studies regarding the functions of ITGB4 in bronchial epithelial cells (BECs), we hypothesize that the decreased ITGB4 expression during embryonic stage leads to abnormal ECM remodeling and increased tissue stiffness, thus impairing BECs motility and compromising lung development. In this study, we examined lung tissue stiffness in normal and ITGB4 deficiency mice using Atomic Force Microscopy (AFM), and demonstrated that ITGB4 deficiency resulted in increased lung tissue stiffness. The examination of ECM components collagen, elastin, and lysyl oxidase (LOX) family showed that the expression of type VI collagen, elastin and LOXL4 were significantly elevated in the ITGB4-deficiency mice, compared with those in normal groups. Airway epithelial cell migration and proliferation capacities on normal and stiff substrates were evaluated through video-microscopy and flow cytometry. The morphology of the cytoskeleton was detected by laser confocal microscopy, and RhoA activities were determined by fluorescence resonance energy transfer (FRET) microscopy. The results showed that migration and proliferation of ITGB4 deficiency cells were noticeably inhibited, along decreased cytoskeleton stabilization, and hampered RhoA activity, especially for cells cultured on the stiff substrate. These results suggest that decreased ITGB4 expression results in increased lung tissue stiffness and impairs the adaptation of bronchial epithelial cells to substrate stiffness, which may be related to the occurrence of broncho pulmonary dysplasia.

A Pan-Cancer Analysis of the Oncogenic Role of Integrin Beta4 (ITGB4) in Human Tumors.

BACKGROUND: Integrin beta4 (ITGB4) is a transmembrane receptor that plays a key role in tumorigenesis and tumor development. However, there are no pan-cancer analyses of ITGB4. METHODS: This study demonstrates the first potential oncogenic roles of ITGB4 across 33 tumors based on the dataset of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). RESULTS: ITGB4 is highly expressed in many cancers, and distinct correlations exist between ITGB4 expression and the prognosis of tumor patients. We also found that the methylation and genetic alteration level of ITGB4 was associated with some cancer prognosis. Furthermore, we found a reduced phosphorylation of ITGB4 at S1457 in several tumors, such as breast and ovarian cancers. Finally, ITGB4 expression was correlated with cancer-associated fibroblasts in liver hepatocellular carcinoma and prostate adenocarcinoma, and the infiltration level of NK cells and neutrophils was observed in other cancers, such as breast invasive carcinoma and lung adenocarcinoma. Moreover, RNA metabolism and protein processing-associated functions are involved in the functional mechanism of ITGB4. CONCLUSION: Our first pan-cancer study may offer a relatively comprehensive understanding of the oncogenic roles of ITGB4 across different tumors.

[The research progress of integrin ß4].

Integrin is a transmembrane receptor that mediates the connection between cells and their external environment, such as extracellular matrix (ECM). Integrin ß4 (ITGß4) plays a number of functions due to its special structures: forms α6ß4 with ITGα6 subunit and participates in the formation of hemidesmosomes; mediates cell-to-cell matrix interaction and cell-to-cell interaction, cell proliferation and survival, as well as migration and invasion. Also, ITGß4 participates in various disease processes by activating multiple signaling pathways. In this paper, the structure, physiological function and function of ITGß4 in respiratory system, tumor, nervous system and other related diseases will be reviewed.