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

Abstract

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.

Controversial roles of cold‑inducible RNA‑binding protein in human cancer (Review)

“…RNA sequencing data obtained from The Cancer Genome Atlas (TCGA) also revealed that the mRNA expression levels of CIRBP are higher in metastatic tissues compared with primary breast tumor samples (79). Similar to previous RNA sequencing data, CIRBP is upregulated in invasive ductal carcinoma (59) and in patient with brain metastases with a high recurrence rate (60). These studies suggest that AUC, area under the ROC curve; C, clinical; CI, confidence interval; CIRBP, cold-inducible RNA-binding protein; DCIS, ductal carcinoma in situ; GEO, gene expression omnibus; HR, hazard ratio; IBC, invasive breast carcinoma; FDR, false discovery rate; IHC, immunohistochemistry; M, distant metastasis; N, regional lymph nodes; NPC, nasopharyngeal carcinoma; NSCLC, non-small cell lung cancer; PAM, prediction analysis of microarrays; OSCC, oral squamous cell carcinoma; T, primary tumor; TCGA, The Cancer Genome Atlas; TMA, tissue microarray; MI, minimally invasive lesion; HI, highly invasive lesion.…”

“…Along with SF, alternative splicing events (ASEs) are also responsible for cancer development and progression (86,87). RNA sequencing and ASE-related datasets of breast cancer samples obtained from TCGA revealed that CIRBP, may serve as a predictor for survival in prognostic-related ASE (59). Together, these results suggest that CIRBP may function as a prognostic marker in a number of cancer types.…”

Severe choline deficiency induces alternative splicing aberrance in optimized duck primary hepatocyte cultures

“…It is reported that DNA mutation is not the only cause of cancer, and AS can also be the killer [46]. New or specific isoforms and disorder isoforms derived from AS are closely related to tumorigenesis and cancer progression [47][48][49]. Accordingly, it is suspected that whether AS events altered in the choline deficient group.…”

Development and Validation of a Novel Immune-Related Prognostic Model and the Potential Mechanism in Metastatic Synovial Sarcoma

“…Li et al constructed 14 immune-related gene prognostic risk assessment models, which showed good predictive performance for the prognosis of patients with osteosarcoma [20]. Huang et al screened 15 alternative splicing genes related to prognosis and two splicing molecules related to bone metastasis to construct a risk assessment model, which showed that the prognosis of breast cancer patients and the occurrence of bone metastasis also have good predictive performance [21]. To the best of our knowledge, there is currently no risk assessment model for immune-related genes in patients with metastatic SS.…”