Neuromedin U and neurotensin may promote the development of the tumour microenvironment in neuroblastoma
Stage 4S neuroblastoma, as defined by the International Neuroblastoma Staging System committee (INSS), is known to regress spontaneously and have a more favourable outcome compared with stage 4 tumours. Comparing the molecular differences between these two stages may provide insights into the progre...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2021-06-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/11512.pdf |
| _version_ | 1797419712656703488 |
|---|---|
| author | Daheng Yang Xianwei Zhang Zheqian Li Fei Xu Chenjie Tang Hongbing Chen |
| author_facet | Daheng Yang Xianwei Zhang Zheqian Li Fei Xu Chenjie Tang Hongbing Chen |
| author_sort | Daheng Yang |
| collection | DOAJ |
| description | Stage 4S neuroblastoma, as defined by the International Neuroblastoma Staging System committee (INSS), is known to regress spontaneously and have a more favourable outcome compared with stage 4 tumours. Comparing the molecular differences between these two stages may provide insights into the progression of neuroblastoma. Our study aimed to explore the molecular differences in the tumour microenvironment (TME) between INSS stage 4S and stage 4 tumours to provide an insight into the mechanisms underlying the biological processes of neuroblastoma. We downloaded the datasets GSE120572 and GSE73517 from the GEO database and pre-processed them using the limma package. CIBERSORT deconvolution agorithm was applied to analyse the differences in 22 infiltrating immune leukocyte subsets between the two stages. We used gene ontology (GO) enrichment analysis to determine the biological process (BP) annotation of differentially expressed genes (DEGs) using the online WebGestalt tool. Hub genes were determined in the STRING database and Cytoscape, and the expression of these genes was verified in the Oncomine database. Then these critical genes were performed survival analysis in TARGET database. We further validated the hub genes using a transwell assay and wound healing assay to detect the function of the genes in the neuroblastoma cell line SK-N-BE(2). GO analysis revealed that the 216 DEGs between stage 4S and stage 4 were enriched in aggressive biological processes. Neuromedin U (NMU) and neurotensin (NTS), which were significantly associated with patients’ overall survival rate, were verified to be elevated in stage 4, and to promote the proliferation and invasion of the SK-N-BE(2) cell. Tumour infiltrating leukocyte analysis showed a high infiltration of regulatory T cells and type 2 tumour-associated macrophages in stage 4 but not in stage 4S. Results of gene co-expression correlation, and the results of previous studies, suggest that NMU and NTS may play certain roles in modulating TME, thus facilitating the progression of neuroblastoma. |
| first_indexed | 2024-03-09T06:51:19Z |
| format | Article |
| id | doaj.art-8e8d2e705f6c47d0a3746b6ad2a45095 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:51:19Z |
| publishDate | 2021-06-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-8e8d2e705f6c47d0a3746b6ad2a450952023-12-03T10:26:22ZengPeerJ Inc.PeerJ2167-83592021-06-019e1151210.7717/peerj.11512Neuromedin U and neurotensin may promote the development of the tumour microenvironment in neuroblastomaDaheng Yang0Xianwei Zhang1Zheqian Li2Fei Xu3Chenjie Tang4Hongbing Chen5Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaWuxi Children’s Hospital, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, ChinaDepartment of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaStage 4S neuroblastoma, as defined by the International Neuroblastoma Staging System committee (INSS), is known to regress spontaneously and have a more favourable outcome compared with stage 4 tumours. Comparing the molecular differences between these two stages may provide insights into the progression of neuroblastoma. Our study aimed to explore the molecular differences in the tumour microenvironment (TME) between INSS stage 4S and stage 4 tumours to provide an insight into the mechanisms underlying the biological processes of neuroblastoma. We downloaded the datasets GSE120572 and GSE73517 from the GEO database and pre-processed them using the limma package. CIBERSORT deconvolution agorithm was applied to analyse the differences in 22 infiltrating immune leukocyte subsets between the two stages. We used gene ontology (GO) enrichment analysis to determine the biological process (BP) annotation of differentially expressed genes (DEGs) using the online WebGestalt tool. Hub genes were determined in the STRING database and Cytoscape, and the expression of these genes was verified in the Oncomine database. Then these critical genes were performed survival analysis in TARGET database. We further validated the hub genes using a transwell assay and wound healing assay to detect the function of the genes in the neuroblastoma cell line SK-N-BE(2). GO analysis revealed that the 216 DEGs between stage 4S and stage 4 were enriched in aggressive biological processes. Neuromedin U (NMU) and neurotensin (NTS), which were significantly associated with patients’ overall survival rate, were verified to be elevated in stage 4, and to promote the proliferation and invasion of the SK-N-BE(2) cell. Tumour infiltrating leukocyte analysis showed a high infiltration of regulatory T cells and type 2 tumour-associated macrophages in stage 4 but not in stage 4S. Results of gene co-expression correlation, and the results of previous studies, suggest that NMU and NTS may play certain roles in modulating TME, thus facilitating the progression of neuroblastoma.https://peerj.com/articles/11512.pdfNeuroblastomaTumour microenvironmentNeuromedin UNeurotensinINSS stage |
| spellingShingle | Daheng Yang Xianwei Zhang Zheqian Li Fei Xu Chenjie Tang Hongbing Chen Neuromedin U and neurotensin may promote the development of the tumour microenvironment in neuroblastoma PeerJ Neuroblastoma Tumour microenvironment Neuromedin U Neurotensin INSS stage |
| title | Neuromedin U and neurotensin may promote the development of the tumour microenvironment in neuroblastoma |
| title_full | Neuromedin U and neurotensin may promote the development of the tumour microenvironment in neuroblastoma |
| title_fullStr | Neuromedin U and neurotensin may promote the development of the tumour microenvironment in neuroblastoma |
| title_full_unstemmed | Neuromedin U and neurotensin may promote the development of the tumour microenvironment in neuroblastoma |
| title_short | Neuromedin U and neurotensin may promote the development of the tumour microenvironment in neuroblastoma |
| title_sort | neuromedin u and neurotensin may promote the development of the tumour microenvironment in neuroblastoma |
| topic | Neuroblastoma Tumour microenvironment Neuromedin U Neurotensin INSS stage |
| url | https://peerj.com/articles/11512.pdf |
| work_keys_str_mv | AT dahengyang neuromedinuandneurotensinmaypromotethedevelopmentofthetumourmicroenvironmentinneuroblastoma AT xianweizhang neuromedinuandneurotensinmaypromotethedevelopmentofthetumourmicroenvironmentinneuroblastoma AT zheqianli neuromedinuandneurotensinmaypromotethedevelopmentofthetumourmicroenvironmentinneuroblastoma AT feixu neuromedinuandneurotensinmaypromotethedevelopmentofthetumourmicroenvironmentinneuroblastoma AT chenjietang neuromedinuandneurotensinmaypromotethedevelopmentofthetumourmicroenvironmentinneuroblastoma AT hongbingchen neuromedinuandneurotensinmaypromotethedevelopmentofthetumourmicroenvironmentinneuroblastoma |