Ral GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma

Uterine carcinosarcoma (UCS) is a highly invasive malignant tumor that originated from the uterine epithelium. Many studies suggested that the abnormal changes of alternative splicing (AS) of pre-mRNA are related to the occurrence and metastasis of the tumor. This study investigates the mechanism of...

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Autores principales:	Hongjun Guo, Siqiao Wang, Aiqing Xie, Wenhuizi Sun, Chenlu Wei, Shuyuan Xian, Huabin Yin, Mingxiao Li, Hanlin Sun, Hong Li, Tong Meng, Jie Zhang, Zongqiang Huang
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/41a780605a324a9a8e54100709e540d9
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spelling	oai:doaj.org-article:41a780605a324a9a8e54100709e540d92021-11-08T02:37:24ZRal GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma1875-863010.1155/2021/1484227https://doaj.org/article/41a780605a324a9a8e54100709e540d92021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/1484227https://doaj.org/toc/1875-8630Uterine carcinosarcoma (UCS) is a highly invasive malignant tumor that originated from the uterine epithelium. Many studies suggested that the abnormal changes of alternative splicing (AS) of pre-mRNA are related to the occurrence and metastasis of the tumor. This study investigates the mechanism of alternative splicing events (ASEs) in the tumorigenesis and metastasis of UCS. RNA-seq of UCS samples and alternative splicing event (ASE) data of UCS samples were downloaded from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases, several times. Firstly, we performed the Cox regression analysis to identify the overall survival-related alternative splicing events (OSRASEs). Secondly, a multivariate model was applied to approach the prognostic values of the risk score. Afterwards, a coexpressed network between splicing factors (SFs) and OSRASEs was constructed. In order to explore the relationship between the potential prognostic signaling pathways and OSRASEs, we fabricated a network between these pathways and OSRASEs. Finally, validations from multidimension platforms were used to explain the results unambiguously. 1,040 OSRASEs were identified by Cox regression. Then, 6 OSRASEs were incorporated in a multivariable model by Lasso regression. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve was 0.957. The risk score rendered from the multivariate model was corroborated to be an independent prognostic factor (P<0.001). In the network of SFs and ASEs, junction plakoglobin (JUP) noteworthily regulated RALGPS1-87608-AT (P<0.001, R=0.455). Additionally, RALGPS1-87608-AT (P=0.006) showed a prominent relationship with distant metastasis. KEGG pathways related to prognosis of UCS were selected by gene set variation analysis (GSVA). The pyrimidine metabolism (P<0.001, R=−0.470) was the key pathway coexpressed with RALGPS1. We considered that aberrant JUP significantly regulated RALGPS1-87608-AT and the pyrimidine metabolism pathway might play a significant part in the metastasis and prognosis of UCS.Hongjun GuoSiqiao WangAiqing XieWenhuizi SunChenlu WeiShuyuan XianHuabin YinMingxiao LiHanlin SunHong LiTong MengJie ZhangZongqiang HuangHindawi LimitedarticleMedicine (General)R5-920ENDisease Markers, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Hongjun Guo Siqiao Wang Aiqing Xie Wenhuizi Sun Chenlu Wei Shuyuan Xian Huabin Yin Mingxiao Li Hanlin Sun Hong Li Tong Meng Jie Zhang Zongqiang Huang Ral GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma
description	Uterine carcinosarcoma (UCS) is a highly invasive malignant tumor that originated from the uterine epithelium. Many studies suggested that the abnormal changes of alternative splicing (AS) of pre-mRNA are related to the occurrence and metastasis of the tumor. This study investigates the mechanism of alternative splicing events (ASEs) in the tumorigenesis and metastasis of UCS. RNA-seq of UCS samples and alternative splicing event (ASE) data of UCS samples were downloaded from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases, several times. Firstly, we performed the Cox regression analysis to identify the overall survival-related alternative splicing events (OSRASEs). Secondly, a multivariate model was applied to approach the prognostic values of the risk score. Afterwards, a coexpressed network between splicing factors (SFs) and OSRASEs was constructed. In order to explore the relationship between the potential prognostic signaling pathways and OSRASEs, we fabricated a network between these pathways and OSRASEs. Finally, validations from multidimension platforms were used to explain the results unambiguously. 1,040 OSRASEs were identified by Cox regression. Then, 6 OSRASEs were incorporated in a multivariable model by Lasso regression. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve was 0.957. The risk score rendered from the multivariate model was corroborated to be an independent prognostic factor (P<0.001). In the network of SFs and ASEs, junction plakoglobin (JUP) noteworthily regulated RALGPS1-87608-AT (P<0.001, R=0.455). Additionally, RALGPS1-87608-AT (P=0.006) showed a prominent relationship with distant metastasis. KEGG pathways related to prognosis of UCS were selected by gene set variation analysis (GSVA). The pyrimidine metabolism (P<0.001, R=−0.470) was the key pathway coexpressed with RALGPS1. We considered that aberrant JUP significantly regulated RALGPS1-87608-AT and the pyrimidine metabolism pathway might play a significant part in the metastasis and prognosis of UCS.
format	article
author	Hongjun Guo Siqiao Wang Aiqing Xie Wenhuizi Sun Chenlu Wei Shuyuan Xian Huabin Yin Mingxiao Li Hanlin Sun Hong Li Tong Meng Jie Zhang Zongqiang Huang
author_facet	Hongjun Guo Siqiao Wang Aiqing Xie Wenhuizi Sun Chenlu Wei Shuyuan Xian Huabin Yin Mingxiao Li Hanlin Sun Hong Li Tong Meng Jie Zhang Zongqiang Huang
author_sort	Hongjun Guo
title	Ral GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma
title_short	Ral GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma
title_full	Ral GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma
title_fullStr	Ral GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma
title_full_unstemmed	Ral GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma
title_sort	ral gef with the ph domain and sh3 binding motif 1 regulated by splicing factor junction plakoglobin and pyrimidine metabolism are prognostic in uterine carcinosarcoma
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/41a780605a324a9a8e54100709e540d9
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Ral GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma

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