ExoBCD: a comprehensive database for exosomal biomarker discovery in breast cancer.

Effective and safe implementation of precision oncology for breast cancer is a vital strategy to improve patient outcomes, which relies on the application of reliable biomarkers. As 'liquid biopsy' and novel resource for biomarkers, exosomes provide a promising avenue for the diagnosis and treatment of breast cancer. Although several exosome-related databases have been developed, there is still lacking of an integrated database for exosome-based biomarker discovery. To this end, a comprehensive database ExoBCD (https://exobcd.liumwei.org) was constructed with the combination of robust analysis of four high-throughput datasets, transcriptome validation of 1191 TCGA cases and manual mining of 950 studies. In ExoBCD, approximately 20 900 annotation entries were integrated from 25 external sources and 306 exosomal molecules (49 potential biomarkers and 257 biologically interesting molecules). The latter could be divided into 3 molecule types, including 121 mRNAs, 172 miRNAs and 13 lncRNAs. Thus, the well-linked information about molecular characters, experimental biology, gene expression patterns, overall survival, functional evidence, tumour stage and clinical use were fully integrated. As a data-driven and literature-based paradigm proposed of biomarker discovery, this study also demonstrated the corroborative analysis and identified 36 promising molecules, as well as the most promising prognostic biomarkers, IGF1R and FRS2. Taken together, ExoBCD is the first well-corroborated knowledge base for exosomal studies of breast cancer. It not only lays a foundation for subsequent studies but also strengthens the studies of probing molecular mechanisms, discovering biomarkers and developing meaningful clinical use.

Identification of Potential Biomarkers for Anti-PD-1 Therapy in Melanoma by Weighted Correlation Network Analysis.

Melanoma is the most malignant form of skin cancer, which seriously threatens human life and health. Anti-PD-1 immunotherapy has shown clinical benefits in improving patients' overall survival, but some melanoma patients failed to respond. Effective therapeutic biomarkers are vital to evaluate and optimize benefits from anti-PD-1 treatment. Although the establishment of immunotherapy biomarkers is well underway, studies that identify predictors by gene network-based approaches are lacking. Here, we retrieved the existing datasets (GSE91061, GSE78220 and GSE93157, 79 samples in total) on anti-PD-1 therapy to explore potential therapeutic biomarkers in melanoma using weighted correlation network analysis (WGCNA), function validation and clinical corroboration. As a result, 13 hub genes as critical nodes were traced from the key module associated with clinical features. After receiver operating characteristic (ROC) curve validation by an independent dataset (GSE78220), six hub genes with diagnostic significance were further recovered. Moreover, these six genes were revealed to be closely associated not only with the immune system regulation, immune infiltration, and validated immunotherapy biomarkers, but also with excellent prognostic value and significant expression level in melanoma. The random forest prediction model constructed using these six genes presented a great diagnostic ability for anti-PD-1 immunotherapy response. Taken together, IRF1, JAK2, CD8A, IRF8, STAT5B, and SELL may serve as predictive therapeutic biomarkers for melanoma and could facilitate future anti-PD-1 therapy.