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.

Characterization of the immune cell infiltration landscape in myxofibrosarcoma to aid immunotherapy.

Myxofibrosarcoma (MFS) is a highly malignant subtype of soft tissue sarcoma, accounting for 5% of cases. Immunotherapy guided by immune cell infiltration (ICI) is reportedly a promising treatment strategy. Here, MFS samples (n = 104) from two independent databases were classified as ICI clusters A/B/C and gene clusters A/B/C. Then, a close relationship between ICI and gene clusters was established. We found that the features of these clusters were consistent with the characteristics of immune-inflamed tumors (cluster C), immune-desert tumors (cluster B), and immune-excluded tumors (cluster A). Moreover, cluster C was sensitive to immunotherapy. Finally, an independent ICI score was established to predict the therapeutic effect, which has prospects for application in guiding immunotherapy during clinical practice.