The landscape of enhancer RNA identify prognosis‐related molecular subtypes in gastric cancer
Abstract Background Enhancer RNAs (eRNAs), the transcriptional products of active enhancers, are of great significance in the initial progression of cancers. However, the biological function and bioinformatics profiles of eRNA in gastric cancer remains largely enigmatic. Methods Firstly, STAD were c...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.4959 |
| _version_ | 1811176406452797440 |
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| author | Aiting Yan Ying Chen Rongrong Bian Cuizhu Wang Haitao Que Yucheng Shen Xiaomin Lu |
| author_facet | Aiting Yan Ying Chen Rongrong Bian Cuizhu Wang Haitao Que Yucheng Shen Xiaomin Lu |
| author_sort | Aiting Yan |
| collection | DOAJ |
| description | Abstract Background Enhancer RNAs (eRNAs), the transcriptional products of active enhancers, are of great significance in the initial progression of cancers. However, the biological function and bioinformatics profiles of eRNA in gastric cancer remains largely enigmatic. Methods Firstly, STAD were clustered into three subtypes with the data of eRNA expression from TCeA. Then we explored the difference of the tumor immune microenvironment, transcription levels, and transcription regulation among the three clusters. Finally, samples collected from 12 patients diagnosed with STAD were used to conduct qRT‐PCR, verifying the conclusion based on network database. Results The three clusters were detected to have different tumor microenvironments: Cluster A has an immune “cold” microenvironment. While cluster B features as more infiltration of immune cells, accompanied with higher expression of immune checkpoints such as PDCD1, LAG3, and TIGIT. Besides, Cluster C shows a higher stromal feature with B lineage, neutrophils, and fibroblasts. Further analyses indicated that CpG island methylation level of Cluster B is different from the other two clusters. Meanwhile, Cluster A and B showed significant enrichment of TP53 and KRAS mutation respectively while Cluster C has higher tumor mutation burden (TMB) and microsatellite instability (MSI). With the elaboration of transcriptional regulation of epigenetic clustering, we detected that Cluster A enriched in epithelial phenotype pathways. Cluster B enriched in cell–cell adhesion. Cluster C enriched in fibroblast proliferation. The clinical cohort show that Cluster B patients have lower interstitial cell characteristics and CAF infiltration. Conclusion We identified three unique epigenetic clusters of STAD through the differential activation of super‐enhancers, and identified Cluster B with a higher immune infiltrating and a better prognosis, which provides a novel understanding of eRNAs and potential clinical applicability of eRNA‐based molecular subtypes in gastric cancer. |
| first_indexed | 2024-04-10T19:52:04Z |
| format | Article |
| id | doaj.art-c1af47b9bf4648919a6c221eb316ee58 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-10T19:52:04Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-c1af47b9bf4648919a6c221eb316ee582023-01-28T05:30:05ZengWileyCancer Medicine2045-76342023-01-011222046205710.1002/cam4.4959The landscape of enhancer RNA identify prognosis‐related molecular subtypes in gastric cancerAiting Yan0Ying Chen1Rongrong Bian2Cuizhu Wang3Haitao Que4Yucheng Shen5Xiaomin Lu6Department of Oncology Affiliated Haian Hospital of Nantong University Nantong Jiangsu ChinaDepartment of Oncology The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third people's hospital Yancheng Jiangsu ChinaDepartment of Oncology, Nanjing Liuhe People Hospital Nanjing Jiangsu ChinaDepartment of Oncology Affiliated Haian Hospital of Nantong University Nantong Jiangsu ChinaDepartment of Oncology Affiliated Haian Hospital of Nantong University Nantong Jiangsu ChinaDepartment of Oncology Affiliated Haian Hospital of Nantong University Nantong Jiangsu ChinaDepartment of Oncology Affiliated Haian Hospital of Nantong University Nantong Jiangsu ChinaAbstract Background Enhancer RNAs (eRNAs), the transcriptional products of active enhancers, are of great significance in the initial progression of cancers. However, the biological function and bioinformatics profiles of eRNA in gastric cancer remains largely enigmatic. Methods Firstly, STAD were clustered into three subtypes with the data of eRNA expression from TCeA. Then we explored the difference of the tumor immune microenvironment, transcription levels, and transcription regulation among the three clusters. Finally, samples collected from 12 patients diagnosed with STAD were used to conduct qRT‐PCR, verifying the conclusion based on network database. Results The three clusters were detected to have different tumor microenvironments: Cluster A has an immune “cold” microenvironment. While cluster B features as more infiltration of immune cells, accompanied with higher expression of immune checkpoints such as PDCD1, LAG3, and TIGIT. Besides, Cluster C shows a higher stromal feature with B lineage, neutrophils, and fibroblasts. Further analyses indicated that CpG island methylation level of Cluster B is different from the other two clusters. Meanwhile, Cluster A and B showed significant enrichment of TP53 and KRAS mutation respectively while Cluster C has higher tumor mutation burden (TMB) and microsatellite instability (MSI). With the elaboration of transcriptional regulation of epigenetic clustering, we detected that Cluster A enriched in epithelial phenotype pathways. Cluster B enriched in cell–cell adhesion. Cluster C enriched in fibroblast proliferation. The clinical cohort show that Cluster B patients have lower interstitial cell characteristics and CAF infiltration. Conclusion We identified three unique epigenetic clusters of STAD through the differential activation of super‐enhancers, and identified Cluster B with a higher immune infiltrating and a better prognosis, which provides a novel understanding of eRNAs and potential clinical applicability of eRNA‐based molecular subtypes in gastric cancer.https://doi.org/10.1002/cam4.4959eRNAsgastric cancerimmune microenvironmentmethylationmutation |
| spellingShingle | Aiting Yan Ying Chen Rongrong Bian Cuizhu Wang Haitao Que Yucheng Shen Xiaomin Lu The landscape of enhancer RNA identify prognosis‐related molecular subtypes in gastric cancer Cancer Medicine eRNAs gastric cancer immune microenvironment methylation mutation |
| title | The landscape of enhancer RNA identify prognosis‐related molecular subtypes in gastric cancer |
| title_full | The landscape of enhancer RNA identify prognosis‐related molecular subtypes in gastric cancer |
| title_fullStr | The landscape of enhancer RNA identify prognosis‐related molecular subtypes in gastric cancer |
| title_full_unstemmed | The landscape of enhancer RNA identify prognosis‐related molecular subtypes in gastric cancer |
| title_short | The landscape of enhancer RNA identify prognosis‐related molecular subtypes in gastric cancer |
| title_sort | landscape of enhancer rna identify prognosis related molecular subtypes in gastric cancer |
| topic | eRNAs gastric cancer immune microenvironment methylation mutation |
| url | https://doi.org/10.1002/cam4.4959 |
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