Prognostic Value and Potential Regulatory Mechanism of Alternative Splicing in Geriatric Breast Cancer
Breast cancer has the highest mortality and morbidity among women, especially in elderly women over 60 years old. Abnormal alternative splicing (AS) events are associated with the occurrence and development of geriatric breast cancer (GBC), yet strong evidence is lacking for the prognostic value of...
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doaj-67d353987f3c4a608a921c908f6fb3862020-11-25T02:37:02ZengMDPI AGGenes2073-44252020-02-0111220010.3390/genes11020200genes11020200Prognostic Value and Potential Regulatory Mechanism of Alternative Splicing in Geriatric Breast CancerXin Li0Yaxuan Wang1Bingjie Li2Wang Ma3School of Medicine, Henan Polytechnic University, Jiaozuo 454150, Henan, ChinaSchool of Medicine, Henan Polytechnic University, Jiaozuo 454150, Henan, ChinaSchool of Medicine, Henan Polytechnic University, Jiaozuo 454150, Henan, ChinaSchool of Medicine, Henan Polytechnic University, Jiaozuo 454150, Henan, ChinaBreast cancer has the highest mortality and morbidity among women, especially in elderly women over 60 years old. Abnormal alternative splicing (AS) events are associated with the occurrence and development of geriatric breast cancer (GBC), yet strong evidence is lacking for the prognostic value of AS in GBC and the regulatory network of AS in GBC, which may highlight the mechanism through which AS contributes to GBC. In the present study, we obtained splicing event information (SpliceSeq) and clinical information for GBC from The Cancer Genome Atlas, and we constructed a GBC prognosis model based on AS events to predict the survival outcomes of GBC. Kaplan−Meier analysis was conducted to evaluate the predictive accuracy among different molecular subtypes of GBC. We conducted enrichment analysis and constructed a splicing network between AS and the splicing factor (SF) to examine the possible regulatory mechanisms of AS in GBC. We constructed eight prognostic signatures with very high statistical accuracy in predicting GBC survival outcomes from 45,421 AS events of 10,480 genes detected in 462 GBC patients; the prognostic model based on exon skip (ES) events had the highest accuracy, indicating its significant value in GBC prognosis. The constructed regulatory SF−AS network may explain the potential regulatory mechanism between SF and AS, which may be the mechanism through which AS events contribute to GBC survival outcomes. The findings confirm that AS events have a significant prognostic value in GBC, and we found a few effective prognostic signatures. We also hypothesized the mechanism underlying AS in GBC and discovered a potential regulatory mechanism between SF and AS.https://www.mdpi.com/2073-4425/11/2/200alternative splicinggeriatric breast cancersplicing factors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xin Li Yaxuan Wang Bingjie Li Wang Ma |
spellingShingle |
Xin Li Yaxuan Wang Bingjie Li Wang Ma Prognostic Value and Potential Regulatory Mechanism of Alternative Splicing in Geriatric Breast Cancer Genes alternative splicing geriatric breast cancer splicing factors |
author_facet |
Xin Li Yaxuan Wang Bingjie Li Wang Ma |
author_sort |
Xin Li |
title |
Prognostic Value and Potential Regulatory Mechanism of Alternative Splicing in Geriatric Breast Cancer |
title_short |
Prognostic Value and Potential Regulatory Mechanism of Alternative Splicing in Geriatric Breast Cancer |
title_full |
Prognostic Value and Potential Regulatory Mechanism of Alternative Splicing in Geriatric Breast Cancer |
title_fullStr |
Prognostic Value and Potential Regulatory Mechanism of Alternative Splicing in Geriatric Breast Cancer |
title_full_unstemmed |
Prognostic Value and Potential Regulatory Mechanism of Alternative Splicing in Geriatric Breast Cancer |
title_sort |
prognostic value and potential regulatory mechanism of alternative splicing in geriatric breast cancer |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2020-02-01 |
description |
Breast cancer has the highest mortality and morbidity among women, especially in elderly women over 60 years old. Abnormal alternative splicing (AS) events are associated with the occurrence and development of geriatric breast cancer (GBC), yet strong evidence is lacking for the prognostic value of AS in GBC and the regulatory network of AS in GBC, which may highlight the mechanism through which AS contributes to GBC. In the present study, we obtained splicing event information (SpliceSeq) and clinical information for GBC from The Cancer Genome Atlas, and we constructed a GBC prognosis model based on AS events to predict the survival outcomes of GBC. Kaplan−Meier analysis was conducted to evaluate the predictive accuracy among different molecular subtypes of GBC. We conducted enrichment analysis and constructed a splicing network between AS and the splicing factor (SF) to examine the possible regulatory mechanisms of AS in GBC. We constructed eight prognostic signatures with very high statistical accuracy in predicting GBC survival outcomes from 45,421 AS events of 10,480 genes detected in 462 GBC patients; the prognostic model based on exon skip (ES) events had the highest accuracy, indicating its significant value in GBC prognosis. The constructed regulatory SF−AS network may explain the potential regulatory mechanism between SF and AS, which may be the mechanism through which AS events contribute to GBC survival outcomes. The findings confirm that AS events have a significant prognostic value in GBC, and we found a few effective prognostic signatures. We also hypothesized the mechanism underlying AS in GBC and discovered a potential regulatory mechanism between SF and AS. |
topic |
alternative splicing geriatric breast cancer splicing factors |
url |
https://www.mdpi.com/2073-4425/11/2/200 |
work_keys_str_mv |
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