The role of tetraspanins pan-cancer.

Tetraspanins (TSPANs) are a class of four-transmembrane segmented proteins. The precise functions of TSPANs and their roles in pan-cancer are unclear. In this work, we analyzed TSPAN1, TSPAN10, TSPAN11, TSPAN12, TSPAN13, TSPAN14, TSPAN15, TSPAN16, TSPAN17, TSPAN18, TSPAN18-AS1, TSPAN19, TSPAN2, TSPAN3, TSPAN31, TSPAN32, TSPAN33, TSPAN4, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN9, TSPAN9-IT1 (24 TSPAN family genes) in relation to tumor characteristics from 11,057 TCGA samples across 33 cancer types. On 24 TSPAN family genes, multidimensional studies were conducted, including gene differential expression, immunological subtype analysis, clinical analysis, stemness indices analysis, drug sensitivity analysis, alteration analysis, and multi-omics validation (including ATAC-seq validation, single-cell sequencing validation, and other external validation). Genes were differentially expressed in 33 cancers, and several of them showed high consistency in terms of tumor characteristics. In particular, the potential roles of TSPAN15 and TSPAN1 in cancer deserve further attention.

The Construction of Bone Metastasis-Specific Prognostic Model and Co-expressed Network of Alternative Splicing in Breast Cancer.

BACKGROUND: Breast cancer (BRCA) ranks among the top most common female malignancies and was regarded as incurable when combined with bone and distant metastasis. Alternative splicing events (ASEs) together with splicing factors (SFs) were considered responsible for the development and progression of tumors. METHODS: Datasets including RNA sequencing and ASEs of BRCA samples were achieved from TCGA and TCGASpliceSeq databases. Then, a survival model was built including 15 overall-survival-associated splicing events (OS-SEs) by Cox regression and Lasso regression. The co-expressed SFs of each bone-and-distant-metastasis-related OS-SE were discovered by Pearson correlation analysis. Additionally, Gene Set Variation Analysis (GSVA) was performed to identify the downstream mechanisms of the key OS-SEs. Finally, the results were validated in different online platforms. RESULTS: A reliable survival model was established (the area under ROC = 0.856), and CIRBP was found co-expressed with FAM110B (R = 0.320, P < 0.001) associated with the fatty acid metabolism pathway. CONCLUSION: Aberrant SF, CIRBP, regulated a specific ASE, exon skip (ES) of FAM110B, during which the fatty acid metabolism pathway played an essential part in tumorigenesis and prognosis of BRCA.