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Alternative splicing implicated in immunity and prognosis of colon adenocarcinoma |
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| Institution: | 1. Department of Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, China;2. Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China;3. Department of Clinical Laboratory, the Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China |
| Abstract: | Dysregulation of immune system is the hallmark of colon adenocarcinoma (COAD) patients. Aberrant alternative splicing (AS) is closely related to progression and immunotherapy of COAD. However, the intrinsic correlation of immune system with AS have not been elucidated. Here we identified 640 AS events related to immunescore by multi-omics data analysis. 7 key AS events were screened out and used to develop a riskscore model, the area under the ROC curve of riskscore model predicting 3-, 5-year survival probability was 0.750, 0.768. Also, the riskscore based on 7 key AS events is an independent prognostic factor. The AUC of the nomogram composed of riskscore and TMN grade reached to 0.872(3-year) and 0.841(5-year). Moreover, 11 AS events were identified to be associated with the infiltration of 8 types of immune cells. Interestingly, M1 macrophages and memory B cells had a higher infiltration in high-riskscore patients, and higher infiltration of M1 macrophages and memory B cells were significantly associated with worse prognosis. In conclusion, AS are closely related to immunescore, immunity stage and infiltrating immune cells. The riskscore is an effective diagnostic and prognostic indicator better than TMN grade, and AS events related to the immune system may be potential therapeutic targets for COAD. |
| Keywords: | Colon adenocarcinoma Alternative splicing Immune system Immune cells Nomogram TCGA"} {"#name":"keyword" "$":{"id":"k0035"} "$$":[{"#name":"text" "_":"The Cancer Genome Atlas AUC"} {"#name":"keyword" "$":{"id":"k0045"} "$$":[{"#name":"text" "_":"The Area Under Curve COAD"} {"#name":"keyword" "$":{"id":"k0055"} "$$":[{"#name":"text" "_":"colon adenocarcinoma AS"} {"#name":"keyword" "$":{"id":"k0065"} "$$":[{"#name":"text" "_":"Alternative Splicing CRC"} {"#name":"keyword" "$":{"id":"k0075"} "$$":[{"#name":"text" "_":"colorectal cancer NSCLC"} {"#name":"keyword" "$":{"id":"k0085"} "$$":[{"#name":"text" "_":"non-small cell lung cancer AA"} {"#name":"keyword" "$":{"id":"k0095"} "$$":[{"#name":"text" "_":"Alternate Acceptor site AD"} {"#name":"keyword" "$":{"id":"k0105"} "$$":[{"#name":"text" "_":"Alternate Donor site AP"} {"#name":"keyword" "$":{"id":"k0115"} "$$":[{"#name":"text" "_":"Alternate Promoter AT"} {"#name":"keyword" "$":{"id":"k0125"} "$$":[{"#name":"text" "_":"Alternate Terminator ES"} {"#name":"keyword" "$":{"id":"k0135"} "$$":[{"#name":"text" "_":"Exon Skip ME"} {"#name":"keyword" "$":{"id":"k0145"} "$$":[{"#name":"text" "_":"Mutually Exclusive Exons RI"} {"#name":"keyword" "$":{"id":"k0155"} "$$":[{"#name":"text" "_":"Retained Intron SNV"} {"#name":"keyword" "$":{"id":"k0165"} "$$":[{"#name":"text" "_":"Single Nucleotide Variants PSI"} {"#name":"keyword" "$":{"id":"k0175"} "$$":[{"#name":"text" "_":"Percent Spliced In ROC"} {"#name":"keyword" "$":{"id":"k0185"} "$$":[{"#name":"text" "_":"Receiver Operating Characteristic SF"} {"#name":"keyword" "$":{"id":"k0195"} "$$":[{"#name":"text" "_":"Splicing Factor TCR"} {"#name":"keyword" "$":{"id":"k0205"} "$$":[{"#name":"text" "_":"T cell receptor FDR"} {"#name":"keyword" "$":{"id":"k0215"} "$$":[{"#name":"text" "_":"false discovery rate |
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