Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome
Introduction Neuroblastoma is the most common extracranial solid tumor in children. Patients with high-risk neuroblastoma have a 5-year survival rate less than 50% after extensive treatment. Signaling pathways control cell fate decisions that dictate the behavior of tumor cells. The deregulation of...
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Format: | Article |
Language: | English |
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SAGE Publishing
2023-05-01
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Series: | Cancer Control |
Online Access: | https://doi.org/10.1177/10732748231178177 |
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author | Xin Li Yanlong Zheng Qiao Ge Zhenbo Dai Dejun Zhou Xiangdong Tian |
author_facet | Xin Li Yanlong Zheng Qiao Ge Zhenbo Dai Dejun Zhou Xiangdong Tian |
author_sort | Xin Li |
collection | DOAJ |
description | Introduction Neuroblastoma is the most common extracranial solid tumor in children. Patients with high-risk neuroblastoma have a 5-year survival rate less than 50% after extensive treatment. Signaling pathways control cell fate decisions that dictate the behavior of tumor cells. The deregulation of signaling pathways is etiological in cancer cells. Thus, we speculated that the pathway activity of neuroblastoma contains more prognostic information and therapeutic targets. Methods Using a footprint-based method, we calculated the activity of fourteen pathways in neuroblastoma. Through stepwise Cox regression analyses, we established a three-gene prognostic signature whose predictive performance was evaluated by external validation. Combining a single-cell sequencing dataset, the most active pathways in high-risk neuroblastoma were found. Results We found that several pathway activities were correlated with neuroblastoma outcomes. We built a three-gene model comprising DLK1, FLT3, and NTRK1, which exhibited superior internal and external performances. We created a nomogram that combines clinical characteristics to aid in the selection and visualization of high-risk neuroblastoma patients. Furthermore, by integrating a single-cell sequencing dataset, we found that estrogen and MAPK were the most active pathways in high-risk neuroblastoma. Conclusion Our findings suggest that pathway-related therapies may hold promise for the treatment of high-risk neuroblastoma. |
first_indexed | 2024-03-11T12:00:35Z |
format | Article |
id | doaj.art-37d89c34c1da45b281ac08017ba79a21 |
institution | Directory Open Access Journal |
issn | 1526-2359 |
language | English |
last_indexed | 2024-03-11T12:00:35Z |
publishDate | 2023-05-01 |
publisher | SAGE Publishing |
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series | Cancer Control |
spelling | doaj.art-37d89c34c1da45b281ac08017ba79a212023-11-08T06:03:19ZengSAGE PublishingCancer Control1526-23592023-05-013010.1177/10732748231178177Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma OutcomeXin LiYanlong ZhengQiao GeZhenbo DaiDejun ZhouXiangdong TianIntroduction Neuroblastoma is the most common extracranial solid tumor in children. Patients with high-risk neuroblastoma have a 5-year survival rate less than 50% after extensive treatment. Signaling pathways control cell fate decisions that dictate the behavior of tumor cells. The deregulation of signaling pathways is etiological in cancer cells. Thus, we speculated that the pathway activity of neuroblastoma contains more prognostic information and therapeutic targets. Methods Using a footprint-based method, we calculated the activity of fourteen pathways in neuroblastoma. Through stepwise Cox regression analyses, we established a three-gene prognostic signature whose predictive performance was evaluated by external validation. Combining a single-cell sequencing dataset, the most active pathways in high-risk neuroblastoma were found. Results We found that several pathway activities were correlated with neuroblastoma outcomes. We built a three-gene model comprising DLK1, FLT3, and NTRK1, which exhibited superior internal and external performances. We created a nomogram that combines clinical characteristics to aid in the selection and visualization of high-risk neuroblastoma patients. Furthermore, by integrating a single-cell sequencing dataset, we found that estrogen and MAPK were the most active pathways in high-risk neuroblastoma. Conclusion Our findings suggest that pathway-related therapies may hold promise for the treatment of high-risk neuroblastoma.https://doi.org/10.1177/10732748231178177 |
spellingShingle | Xin Li Yanlong Zheng Qiao Ge Zhenbo Dai Dejun Zhou Xiangdong Tian Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome Cancer Control |
title | Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome |
title_full | Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome |
title_fullStr | Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome |
title_full_unstemmed | Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome |
title_short | Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome |
title_sort | integrating bulk seq and single cell seq reveals estrogen and mapk pathways associating with neuroblastoma outcome |
url | https://doi.org/10.1177/10732748231178177 |
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