Identification of Prognostic alternative splicing signatures and their clinical significance in uveal melanoma

Zhou, Wei; Fei, Ping; Li, Jing

doi:10.1016/j.exer.2021.108666

Cited by 3 publications

(3 citation statements)

References 30 publications

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“…Among these, most reports focus on the relationship between aberrant ASEs and prognosis and survival in cancer patients. After identification of the overall survival-associated ASEs, prognostic models were developed to predict the survival outcomes of patients with aberrant AS patterns in gastric cancer ( 32 – 35 ), breast cancer ( 36 ), CHOL ( 37 ), glioblastoma ( 38 ), pancreatic cancer ( 39 ), LAML ( 40 ), UVM ( 41 ), HNSC ( 42 ), etc. Aberrant AS is also related to chemotherapy resistance.…”

Section: Discussionmentioning

confidence: 99%

Identification of alternative splicing associated with clinical features: from pan-cancers to genitourinary tumors

Duan,

Zhang,

et al. 2023

Front. Oncol.

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BackgroundAlternative splicing events (ASEs) are vital causes of tumor heterogeneity in genitourinary tumors and many other cancers. However, the clinicopathological relevance of ASEs in cancers has not yet been comprehensively characterized.MethodsBy analyzing splicing data from the TCGA SpliceSeq database and phenotype data for all TCGA samples from the UCSC Xena database, we identified differential clinical feature-related ASEs in 33 tumors. CIBERSORT immune cell infiltration data from the TIMER2.0 database were used for differential clinical feature-related immune cell infiltration analysis. Gene function enrichment analysis was used to analyze the gene function of ASEs related to different clinical features in tumors. To reveal the regulatory mechanisms of ASEs, we integrated race-related ASEs and splicing quantitative trait loci (sQTLs) data in kidney renal clear cell carcinoma (KIRC) to comprehensively assess the impact of SNPs on ASEs. In addition, we predicted regulatory RNA binding proteins in bladder urothelial carcinoma (BLCA) based on the enrichment of motifs around alternative exons for ASEs.ResultsAlternative splicing differences were systematically analyzed between different groups of 58 clinical features in 33 cancers, and 30 clinical features in 24 cancer types were identified to be associated with more than 50 ASEs individually. The types of immune cell infiltration were found to be significantly different between subgroups of primary diagnosis and disease type. After integrating ASEs with sQTLs data, we found that 63 (58.9%) of the race-related ASEs were significantly SNP-correlated ASEs in KIRC. Gene function enrichment analyses showed that metastasis-related ASEs in KIRC mainly enriched Rho GTPase signaling pathways. Among those ASEs associated with metastasis, alternative splicing of GIT2 and TUBB3 might play key roles in tumor metastasis in KIRC patients. Finally, we identified several RNA binding proteins such as PCBP2, SNRNP70, and HuR, which might contribute to splicing differences between different groups of neoplasm grade in BLCA.ConclusionWe demonstrated the significant clinical relevance of ASEs in multiple cancer types. Furthermore, we identified and validated alternative splicing of TUBB3 and RNA binding proteins such as PCBP2 as critical regulators in the progression of urogenital cancers.

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Section: Discussionmentioning

confidence: 99%

Identification of alternative splicing associated with clinical features: from pan-cancers to genitourinary tumors

Duan,

Zhang,

et al. 2023

Front. Oncol.

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“…According to the median risk score, we divided UVM cohort into low- and high-risk subgroups. Prognostic model and nomogram were established essentially as described in detail previously ( Zhou et al, 2021a ).…”

Section: Methodsmentioning

confidence: 99%

Integrated Analysis of Genes Associated With Immune Microenvironment and Distant Metastasis in Uveal Melanoma

Zhou

2022

Front. Cell Dev. Biol.

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Inflammatory infiltration plays an essential role in the progression of tumor malignancy. The aim of this study was to identify genes associated with inflammatory microenvironment and clinical traits for survival prediction of uveal melanoma (UVM) patients. The datasets and clinical characteristics of UVM were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We divided the UVM patients into low and high immune cell infiltration groups, identified differentially expressed genes (DEGs), constructed weighted gene co-expression network, and established prognostic prediction model and nomogram for UVM. Our analysis showed that DEGs were enriched in cytokine signaling in immune system, positive regulation of immune response and adaptive immune system. A total of fifteen candidate genes were extracted from DEGs and genes that were positively associated with tumor metastasis. Subsequently, five prognostic genes were selected to construct the final prognostic prediction model, including two up-regulated genes LHFPL3 antisense RNA 1 (LHFPL3-AS1) and LYN proto-oncogene (LYN), and three down-regulated genes SLCO4A1 antisense RNA 1 (SLCO4A1-AS1), Zinc-α2-glycoprotein 1 (AZGP1) and Deleted in Liver Cancer-1 (DLC1) in the high risk group. The model showed an Area Under Curve (AUC) value of 0.877. Our analysis highlighted the importance of immune-related genes in the progression of UVM and also provided potential targets for the immunotherapy of UVM.

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“…RNA mis-splicing is not only capable of causing a vast repertoire of diseases, but also the fundament of occurrence and development of tumors. Increasing evidences indicate that AS changes are vital signatures for tumor progression and therapy [ 11 ]. AS is a sophisticated process, strictly managed by the spliceosome, which is composed of five small nuclear RNAs (snRNA U1, U2, U4, U5 and U6) and a large number of splicing factors (SFs) [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

DAZAP1 facilitates the alternative splicing of KITLG to promote multiple myeloma cell proliferation via ERK signaling pathway

Zhou

Huangfu

et al. 2022

Aging

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Multiple myeloma (MM) is an incurable plasma cell malignancy, in which alternativepre-mRNA splicing (AS) acts as one of the key transcriptome modifier. The Deleted in Azoospermia-Associated Protein 1 (DAZAP1) is a splicing factor that has been identified as an oncogene in multiple cancers, yet its role in MM proliferation remains unclear. We first analyzed MM clinical databases and found that MM patients with elevated DAZAP1 had a poor survival. Furthermore, we overexpressed DAZAP1 by lentiviral transfection and utilized siRNA silencing the expression of DAZAP1 in MM cells. DAZAP1 promoted MM cell proliferation in vitro and accelerated MM xenograft tumor growth in vivo. KEGG pathway enrichment analysis showed that ERK signaling pathway was activated in DAZAP1-OE MM cells. The analyses of RIP-seq and RIP-qPCR revealed that DAZAP1 activated alternative splicing of KIT proto-oncogene ligand (KITLG) mRNA. Further study validated that DAZAP1 increased ERK phosphorylation via modulating alternative splicing of KITLG mRNA to promote MM cell proliferation. In conclusion, we establish DAZAP1 as a tumor-promoting gene with therapeutic potential and provide mechanistic insights into targeting DAZAP1 as a new strategy for the diagnosis and treatment of MM.

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Identification of Prognostic alternative splicing signatures and their clinical significance in uveal melanoma

Cited by 3 publications

References 30 publications

Identification of alternative splicing associated with clinical features: from pan-cancers to genitourinary tumors

Identification of alternative splicing associated with clinical features: from pan-cancers to genitourinary tumors

Integrated Analysis of Genes Associated With Immune Microenvironment and Distant Metastasis in Uveal Melanoma

DAZAP1 facilitates the alternative splicing of KITLG to promote multiple myeloma cell proliferation via ERK signaling pathway

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