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A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer

OBJECTIVE: Ovarian cancer (OV) has a high mortality rate all over the world, and extrachromosomal circular DNA (eccDNA) plays a key role in carcinogenesis. We wish to study more about the molecular structure of eccDNA in the UACC-1598–4 cell line and how its genes are associated with ovarian cancer...

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Autores principales: Zhang, Ying, Dong, Kexian, Jia, Xueyuan, Du, Shuomeng, Wang, Dong, Wang, Liqiang, Qu, Han, Zhu, Shihao, Wang, Yang, Wang, Zhao, Zhang, Shuopeng, Sun, Wenjing, Fu, Songbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278296/
https://www.ncbi.nlm.nih.gov/pubmed/37337170
http://dx.doi.org/10.1186/s12920-023-01576-x
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author Zhang, Ying
Dong, Kexian
Jia, Xueyuan
Du, Shuomeng
Wang, Dong
Wang, Liqiang
Qu, Han
Zhu, Shihao
Wang, Yang
Wang, Zhao
Zhang, Shuopeng
Sun, Wenjing
Fu, Songbin
author_facet Zhang, Ying
Dong, Kexian
Jia, Xueyuan
Du, Shuomeng
Wang, Dong
Wang, Liqiang
Qu, Han
Zhu, Shihao
Wang, Yang
Wang, Zhao
Zhang, Shuopeng
Sun, Wenjing
Fu, Songbin
author_sort Zhang, Ying
collection PubMed
description OBJECTIVE: Ovarian cancer (OV) has a high mortality rate all over the world, and extrachromosomal circular DNA (eccDNA) plays a key role in carcinogenesis. We wish to study more about the molecular structure of eccDNA in the UACC-1598–4 cell line and how its genes are associated with ovarian cancer prognosis. METHODS: We sequenced and annotated the eccDNA by Circle_seq of the OV cell line UACC-1598–4. To acquire the amplified genes of OV on eccDNA, the annotated eccDNA genes were intersected with the overexpression genes of OV in TCGA. Univariate Cox regression was used to find the genes on eccDNA that were linked to OV prognosis. The least absolute shrinkage and selection operator (LASSO) and cox regression models were used to create the OV prognostic model, as well as the receiver operating characteristic curve (ROC) curve and nomogram of the prediction model. By applying the median value of the risk score, the samples were separated into high-risk and low-risk groups, and the differences in immune infiltration between the two groups were examined using ssGSEA. RESULTS: EccDNA in UACC-1598–4 has a length of 0-2000 bp, and some of them include the whole genes or gene fragments. These eccDNA originated from various parts of chromosomes, especially enriched in repeatmasker, introns, and coding regions. They were annotated with 2188 genes by Circle_seq. Notably, the TCGA database revealed that a total of 198 of these eccDNA genes were overexpressed in OV (p < 0.05). They were mostly enriched in pathways associated with cell adhesion, ECM receptors, and actin cytoskeleton. Univariate Cox analysis showed 13 genes associated with OV prognosis. LASSO and Cox regression analysis were used to create a risk model based on remained 9 genes. In both the training (TCGA database) and validation (International Cancer Genome Consortium, ICGC) cohorts, a 9-gene signature could successfully discriminate high-risk individuals (all p < 0.01). Immune infiltration differed significantly between the high-risk and low-risk groups. The model’s area under the ROC curve was 0.67, and a nomograph was created to assist clinician. CONCLUSION: EccDNA is found in UACC-1598–4, and part of its genes linked to OV prognosis. Patients with OV may be efficiently evaluated using a prognostic model based on eccDNA genes, including SLC7A1, NTN1, ADORA1, PADI2, SULT2B1, LINC00665, CILP2, EFNA5, TOMM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01576-x.
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spelling pubmed-102782962023-06-20 A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer Zhang, Ying Dong, Kexian Jia, Xueyuan Du, Shuomeng Wang, Dong Wang, Liqiang Qu, Han Zhu, Shihao Wang, Yang Wang, Zhao Zhang, Shuopeng Sun, Wenjing Fu, Songbin BMC Med Genomics Research OBJECTIVE: Ovarian cancer (OV) has a high mortality rate all over the world, and extrachromosomal circular DNA (eccDNA) plays a key role in carcinogenesis. We wish to study more about the molecular structure of eccDNA in the UACC-1598–4 cell line and how its genes are associated with ovarian cancer prognosis. METHODS: We sequenced and annotated the eccDNA by Circle_seq of the OV cell line UACC-1598–4. To acquire the amplified genes of OV on eccDNA, the annotated eccDNA genes were intersected with the overexpression genes of OV in TCGA. Univariate Cox regression was used to find the genes on eccDNA that were linked to OV prognosis. The least absolute shrinkage and selection operator (LASSO) and cox regression models were used to create the OV prognostic model, as well as the receiver operating characteristic curve (ROC) curve and nomogram of the prediction model. By applying the median value of the risk score, the samples were separated into high-risk and low-risk groups, and the differences in immune infiltration between the two groups were examined using ssGSEA. RESULTS: EccDNA in UACC-1598–4 has a length of 0-2000 bp, and some of them include the whole genes or gene fragments. These eccDNA originated from various parts of chromosomes, especially enriched in repeatmasker, introns, and coding regions. They were annotated with 2188 genes by Circle_seq. Notably, the TCGA database revealed that a total of 198 of these eccDNA genes were overexpressed in OV (p < 0.05). They were mostly enriched in pathways associated with cell adhesion, ECM receptors, and actin cytoskeleton. Univariate Cox analysis showed 13 genes associated with OV prognosis. LASSO and Cox regression analysis were used to create a risk model based on remained 9 genes. In both the training (TCGA database) and validation (International Cancer Genome Consortium, ICGC) cohorts, a 9-gene signature could successfully discriminate high-risk individuals (all p < 0.01). Immune infiltration differed significantly between the high-risk and low-risk groups. The model’s area under the ROC curve was 0.67, and a nomograph was created to assist clinician. CONCLUSION: EccDNA is found in UACC-1598–4, and part of its genes linked to OV prognosis. Patients with OV may be efficiently evaluated using a prognostic model based on eccDNA genes, including SLC7A1, NTN1, ADORA1, PADI2, SULT2B1, LINC00665, CILP2, EFNA5, TOMM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01576-x. BioMed Central 2023-06-19 /pmc/articles/PMC10278296/ /pubmed/37337170 http://dx.doi.org/10.1186/s12920-023-01576-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhang, Ying
Dong, Kexian
Jia, Xueyuan
Du, Shuomeng
Wang, Dong
Wang, Liqiang
Qu, Han
Zhu, Shihao
Wang, Yang
Wang, Zhao
Zhang, Shuopeng
Sun, Wenjing
Fu, Songbin
A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer
title A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer
title_full A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer
title_fullStr A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer
title_full_unstemmed A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer
title_short A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer
title_sort novel extrachromosomal circular dna related genes signature for overall survival prediction in patients with ovarian cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278296/
https://www.ncbi.nlm.nih.gov/pubmed/37337170
http://dx.doi.org/10.1186/s12920-023-01576-x
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