Comprehensive pan-cancer analysis: essential role of ABCB family genes in cancer.

Background: The adenosine triphosphate-binding-cassette (ABC) transporter orchestrates the transmembrane transport of diverse substrates with the aid of ATP as an energy source. ABC transporter constitutes a widespread superfamily of transporters prominently present on the cellular membrane of organisms. Advancements in understanding have unveiled additional roles beyond mere intracellular or extracellular transport functions for the ABC protein family, encompassing involvement in DNA repair, protein translation, and gene expression regulation. Yet its role in tumors is still unknown. Methods: This study drew support from multiple databases, including Gene Expression Omnibus (GEO), European Genome-phenome Archive (EGA), The Cancer Genome Atlas (TCGA), and employed multidimensional bioinformatics analyses, incorporating online databases and the R-project. Through a comprehensive analysis, we seek to discern transcriptional-level disparities among genes and their consequential impacts on prognosis, tumor microenvironment (TME), stemness score, immune subtypes, clinical characteristics, and drug sensitivity across human cancers. Results: ABC transporter subfamily B (ABCB) family genes exhibited heightened expression across diverse tumors, demonstrating a significant correlation with overall prognosis in pan-cancer contexts. Notably, gene expression levels manifested substantial associations with TME, stemness score, immune subtypes, clinical characteristics, and drug sensitivity in specific cancers, including kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD). Within this subset, transporter associated with antigen processing 1 (TAP1), TAP2, and ABCB6 emerged as noteworthy oncogenes. Conclusions: The outcomes of this study contribute to a comprehensive understanding of the implications of ABCB family genes in tumor progression, offering insights into potential therapeutic targets for cancer. Notably, the identification of ABCB6 as a significant oncogene suggests promising avenues for targeted therapies in KIRP, LIHC, and PAAD.

Prognostic and immune implications of a novel 7-methylguanosine-related microRNA signature in breast invasive carcinoma: from exploration to validation.

OBJECTIVES: This study aims to develop and validate a prognostic signature based on 7-methylguanosine-related (M7G-related) miRNAs for predicting prognosis and immune implications in breast invasive carcinoma (BRCA). MATERIALS AND METHODS: M7G-related miRNA data of BRCA were obtained from The Cancer Genome Atlas (TCGA). Least absolute shrinkage and selection operator (LASSO)-penalized, univariate, and multivariate Cox regression analyses were used to construct the prognostic signature. Furthermore, the predictive validity was verified using Kaplan-Meier (KM) survival risk and receiver operating characteristic (ROC) plots. Internal random sampling verification was used to simplify and validate the signature. RT-qPCR was used to quantify the expression level of transcriptional profiles. The independent prognostic role of the risk score was validated using univariate and multivariate regression. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used for functional and immune enrichment analysis. RESULTS: A total of 18 M7G-related miRNAs were identified to construct the prognostic signature in BRCA. The low-risk group exhibited significantly higher overall survival than the high-risk group in the KM survival plot (P < 0.001). The area under the curve (AUC) for 1-, 3-, and 5-year survivals in the ROC curve were 0.737, 0.724, and 0.702, respectively. The survival significance in the training and testing cohorts was confirmed by random sampling verification. The most prominent miRNAs in the signature were the miR-7, miR-139, miR-10b, and miR-4728. Furthermore, immune scores for B, mast, and Th1 cells varied between risk groups. Our research demonstrated that CD52 was the most positively correlated gene with immune cells and functions in BRCA. CONCLUSION: Our study presents a comprehensive and systematic analysis of M7G-related miRNAs to construct a prognostic signature in BRCA. The signature demonstrated excellent prognostic validity, with the risk score as an independent prognostic factor. These results provide critical evidence for further investigation of M7G miRNAs and offer new insights for BRCA patients in the context of effective immunotherapy.

Expression of β-1,4-galactosyltransferase I in a surgically-induced rat model of knee osteoarthritic synovitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are few reports of a biological role for glycosyltransferases in the infiltration of osteoarthritic synovitis. The aim of this research was to investigate the expression and cellular location of β-1,4-galactosyltransferase I (β-1,4-GalT-I) in a surgically-induced rat model of knee osteoarthritis (OA), and explore the role of β-1,4-GalT-I in the pathogenesis of OA.</p><p><b>METHODS</b>Male Sprague-Dawley rats were randomly divided into three groups: OA group, sham group and normal group. The model of OA was established in the right knees of rats by anterior cruciate ligament transaction (ACLT) with partial medial meniscectomy. Fibroblast-like synoviocytes (FLSs) obtained from normal rat synovial tissue were cultured. The expression of β-1,4-GalT-I mRNA in the synovial tissue, articular cartilage and FLSs treated with tumor necrosis factor-α (TNF-α) were assayed by real-time PCR. Western-blotting and immunohistochemisty were used to observe the expression of β-1,4-GalT-I at the protein level. Double immunofluorescent staining was used to define the location of the β-1,4-GalT-I with macrophage-like synoviocytes, FLSs, neutrophils, and TNF-α in the OA synovium. The alteration of TNF-α in FLSs which were treated with lipopolysaccharide (LPS) and β-1,4-GalT-I-Ab were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The mRNA and protein expression of β-1,4-GalT-I increased in synovial tissue of the OA group compared with the normal and sham groups at two and four weeks after the surgery, however, no significant difference appeared in the articular cartilage. Immunohistochemistry also indicated that the β-1,4-GalT-I expression in OA synovium at four weeks after surgery increased sharply compared with the control group. β-1,4-GalT-I co-localized with macrophage-like synoviocytes, FLSs, neutrophils and TNF-α in rat OA synovitis. Moreover, in vitro β-1,4-GalT-I mRNA in FLSs was affected in a dose- and time-dependent manner in response to TNF-α stimulation. ELISA revealed that the expression of TNF-α was attenuated in FLSs in vitro when treated with anti β-1,4-GalT-I antibody.</p><p><b>CONCLUSION</b>β-1,4-GalT-I may play an important role in the inflammation process of rat OA synovial tissue which would provide the foundation for further researching into the concrete mechanism of β-1,4-GalT-I in OA synovitis.</p>