Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker
Background: Gastric cancer (GC) is the most commonly diagnosed digestive system malignancy with a dismal survival outcome. The prognostic value of ubiquitination-related genes (URGs) in GC has yet to be discovered. Methods: Two GC cohort datasets were obtained from the Cancer Genome Atlas Program (T...
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| Format: | Article |
| Language: | English |
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IMR Press
2023-11-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/28/11/10.31083/j.fbl2811304 |
| _version_ | 1797400703020302336 |
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| author | Zhongting Huang Zhiyong Zhang Yangyang Tu Haibin He Feng Qiu Hailong Qian Chunshu Pan |
| author_facet | Zhongting Huang Zhiyong Zhang Yangyang Tu Haibin He Feng Qiu Hailong Qian Chunshu Pan |
| author_sort | Zhongting Huang |
| collection | DOAJ |
| description | Background: Gastric cancer (GC) is the most commonly diagnosed digestive system malignancy with a dismal survival outcome. The prognostic value of ubiquitination-related genes (URGs) in GC has yet to be discovered. Methods: Two GC cohort datasets were obtained from the Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) databases. Stepwise Cox analysis was employed to generate a signature. Then, we applied unsupervised clustering analysis to determine subclusters in GC based on URGs. Single-cell analysis was carried out to depict the cellular location of model genes. The CIBERSORT method was performed to estimate the immune landscape. Finally, preliminary wet lab work was utilized to disclose the potential effect of OTULIN. Results: Our proposed signature was set up based on five URGs (OTULIN, UBE2C, USP1, USP2, and MAPT) which could serve as a risk classifier to categorize GC cases. In addition, it was demonstrated that the ubiquitination-associated model could depict the immune landscape and forecast immunotherapy response for GC patients. Furthermore, in vitro experiments determined the function and effect of OUTLIN in GC. We observed that the knockdown of OUTLIN could suppress cell viability and metastatic ability of GC cell lines. Conclusions: Our data lays the groundwork for a comprehensive investigation into the role of URGs in GC and determined OTULIN as a candidate GC biomarker. |
| first_indexed | 2024-03-09T01:59:19Z |
| format | Article |
| id | doaj.art-07d0e2f85121402481138412c2d90252 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-09T01:59:19Z |
| publishDate | 2023-11-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-07d0e2f85121402481138412c2d902522023-12-08T07:49:20ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-11-01281130410.31083/j.fbl2811304S2768-6701(23)00959-0Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel BiomarkerZhongting Huang0Zhiyong Zhang1Yangyang Tu2Haibin He3Feng Qiu4Hailong Qian5Chunshu Pan6Department of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital, Ningbo University, 315000 Ningbo, Zhejiang, ChinaDepartment of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital, Ningbo University, 315000 Ningbo, Zhejiang, ChinaDepartment of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital, Ningbo University, 315000 Ningbo, Zhejiang, ChinaDepartment of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital, Ningbo University, 315000 Ningbo, Zhejiang, ChinaDepartment of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital, Ningbo University, 315000 Ningbo, Zhejiang, ChinaDepartment of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital, Ningbo University, 315000 Ningbo, Zhejiang, ChinaDepartment of Radiology, Ningbo No.2 Hospital, 315000 Ningbo, Zhejiang, ChinaBackground: Gastric cancer (GC) is the most commonly diagnosed digestive system malignancy with a dismal survival outcome. The prognostic value of ubiquitination-related genes (URGs) in GC has yet to be discovered. Methods: Two GC cohort datasets were obtained from the Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) databases. Stepwise Cox analysis was employed to generate a signature. Then, we applied unsupervised clustering analysis to determine subclusters in GC based on URGs. Single-cell analysis was carried out to depict the cellular location of model genes. The CIBERSORT method was performed to estimate the immune landscape. Finally, preliminary wet lab work was utilized to disclose the potential effect of OTULIN. Results: Our proposed signature was set up based on five URGs (OTULIN, UBE2C, USP1, USP2, and MAPT) which could serve as a risk classifier to categorize GC cases. In addition, it was demonstrated that the ubiquitination-associated model could depict the immune landscape and forecast immunotherapy response for GC patients. Furthermore, in vitro experiments determined the function and effect of OUTLIN in GC. We observed that the knockdown of OUTLIN could suppress cell viability and metastatic ability of GC cell lines. Conclusions: Our data lays the groundwork for a comprehensive investigation into the role of URGs in GC and determined OTULIN as a candidate GC biomarker.https://www.imrpress.com/journal/FBL/28/11/10.31083/j.fbl2811304gastric cancerubiquitinationprognosisimmunotherapy responseotulin |
| spellingShingle | Zhongting Huang Zhiyong Zhang Yangyang Tu Haibin He Feng Qiu Hailong Qian Chunshu Pan Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker Frontiers in Bioscience-Landmark gastric cancer ubiquitination prognosis immunotherapy response otulin |
| title | Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker |
| title_full | Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker |
| title_fullStr | Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker |
| title_full_unstemmed | Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker |
| title_short | Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker |
| title_sort | integrated single cell and transcriptome sequencing analyses develop a ubiquitination associated signature in gastric cancer and identified otulin as a novel biomarker |
| topic | gastric cancer ubiquitination prognosis immunotherapy response otulin |
| url | https://www.imrpress.com/journal/FBL/28/11/10.31083/j.fbl2811304 |
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