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.

Prognosis Implication of a Novel Metabolism-Related Gene Signature in Ewing Sarcoma.

Ewing sarcoma (ES) is one of the most common bone cancers in adolescents and children. Growing evidence supports the view that metabolism pathways play critical roles in numerous cancers (He et al. (2020)). However, the correlation between metabolism-associated genes (MTGs) and Ewing sarcoma has not been investigated systematically. Here, based on the univariate Cox regression analysis, we get survival genes from differentially expressed genes (DEGs) from Gene Expression Omnibus (GEO) cohort. Multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to establish the MTG signature. Comprehensive survival analyses including receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were applied to estimate the independent prognostic value of the signature. The ICGC cohort served as the validation cohort. A nomogram was constructed based on the risk score of the MTG signature and other independent clinical variables. The CIBERSORT algorithm was applied to estimate immune infiltration. In addition, we explored the correlation between MTG signature and immune checkpoints. Collectively, this work presents a novel MTG signature for prognostic prediction of Ewing sarcoma. It also suggests six genes that are potential prognostic indicators and therapeutic targets for ES.

Rheumatoid arthritis and osteoporosis: a bi-directional Mendelian randomization study.

Many observation studies have demonstrated a close relationship between rheumatoid arthritis (RA) and osteoporosis (OP). However, the causal genetic correlation between RA and OP remains unclear. In this study, we performed bi-directional Mendelian randomization (MR) analyses to explore causal inference between these two traits. The instrumental variables for RA were selected from a large-scale genome-wide association study (GWAS) (1,523 cases and 461,487 controls). Bone mineral density (BMD) at five different sites (heel (n=265,627), forearm (FA) (n=8,143), femoral neck (FN) (n=32,735), lumbar spine (LS) (n=28,498), and total body (n=28,498)) were used as phenotypes for OP. The inverse variance weighted (IVW) method did not detect any causal effect of BMDs on RA except heel BMD (beta = -7.57 × 10-4, p = 0.02). However, other methods (MR-Egger, weighted median, weighted mode, MR-PRESSO, and MR-RAPS) showed no causal association between heel BMD and RA. Likewise, we did not find a causal effect of RA on BMD at any sites. In conclusion, we found no evidence that RA is causally associated with OP/BMD, or vice versa. We suggested that the associations found in previous observational studies between RA and OP/BMD are possibly related to secondary effects such as antirheumatic treatment and reduced physical activity.

Identification of the Roles of Chromobox Family Members in Gastric Cancer: A Study Based on Multiple Datasets.

BACKGROUND: As the important components in polycomb repressive complexes 1 (PRC1) and heterochromatin protein 1 (HP1), Chromobox (CBX) family members are involved in epigenetic regulatory function, transcriptional repression, and other cellular metabolisms. Increasing studies have indicated significant associations between CBX and tumorigenesis, which is a progression in different types of cancers. However, the information about the roles of each CBX in gastric cancer is extremely limited. METHODS: We explored CBX mRNA expression, corrections with clinicopathological parameters, protein expression, prognostic values, enrichment analysis with several databases including Oncomine, Human Protein Atlas, UALCAN, Kaplan-Meier plotter, cBioPortal, GeneMANIA, and Enrichr. RESULTS: In our study, comparing to the normal tissues, higher mRNA expression of CBX1/2/3/4/5/8 and lower mRNA expression of CBX7 were found in GC tissues while upregulations of CBX1/2/3/4/5/8 and downregulations of CBX7 were indicated to be significantly correlated to the nodal metastasis status and individual cancer stages in GC patients. As for protein level, the expression of CBX2/3/4/5/6 was higher and the expression of CBX7 was lower in the GC tissues than those in the normal. What is more, higher mRNA expression of CBX1/5/6/8 and lower mRNA expression of CBX7 were markedly correlated to poor outcomes of OS and FP in GC patients. Besides, high mutation rate of CBXs (42%) was observed in GC patients. CONCLUSIONS: We suggest that CBX5/7 may serve as potential therapeutic targets for GC while CBX1/8 may serve as potential prognostic indicators for GC.