RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma
Abstract Background Recent studies have highlighted the role of RNA modification, that is, the dysregulation of epitranscriptomics, in tumorigenesis and progression. The potential for undoing epigenetic changes may develop novel therapeutic and prognostic approaches. However, the roles of these RNA...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-01-01
|
| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-01791-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594646508765184 |
|---|---|
| author | Qiang Xu Lingyu Kong Zhezhu Han Xiuying Jin Mingyan Ding Zhengri Piao Songnan Zhang |
| author_facet | Qiang Xu Lingyu Kong Zhezhu Han Xiuying Jin Mingyan Ding Zhengri Piao Songnan Zhang |
| author_sort | Qiang Xu |
| collection | DOAJ |
| description | Abstract Background Recent studies have highlighted the role of RNA modification, that is, the dysregulation of epitranscriptomics, in tumorigenesis and progression. The potential for undoing epigenetic changes may develop novel therapeutic and prognostic approaches. However, the roles of these RNA modifications in the tumor microenvironment (TME) are still unknown. Methods We assessed the expression properties and genetic alterations of 26 RNA modification writers, including adenosine-to-inosine RNA editing, alternative polyadenylation, m1A, and m6A in 502 lung adenocarcinoma (LUAD) samples from the Cancer Genome Atlas (TCGA) datasets. Then, we used differentially expressed gene (DEGs) to develop a signature for predicting patient outcomes, which was dubbed the “writer score” for RNA-modified writers. In addition, we analyzed the association between TME features, molecular subtypes, treatment sensitivity, and immunotherapy efficacy. Results We comprehensively evaluated the changes in multilayer RNA modification writers and identified the role of RNA modification writer expression imbalances in LUAD emergence and progression. Additionally, we constructed a risk-score model based on six LUAD prognosis-associated differentially expressed RNA modification writer genes. Kaplan–Meier (K–M) analyses revealed that the low risk-score signature had high overall patient survival. The predictive significance of the risk-score model was demonstrated using both univariate and multivariate Cox analyses. The risk-score model was positively correlated with the immune- and proliferation-related pathways. In response to anti-cancer treatment, high-risk score is related with high TMB, which has been discovered to correlate with immunotherapy effectiveness. Conclusion This study showed a strong correlation between the TME variety, level of complexity, and the four types of RNA modification writers. In addition, this scoring system could potentially predict effective immunotherapy and deepens our understanding of TME characteristics. |
| format | Article |
| id | doaj-art-badd3f170661440ea6d6cba464b7229e |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-badd3f170661440ea6d6cba464b7229e2025-01-19T12:29:15ZengSpringerDiscover Oncology2730-60112025-01-0116111210.1007/s12672-025-01791-1RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinomaQiang Xu0Lingyu Kong1Zhezhu Han2Xiuying Jin3Mingyan Ding4Zhengri Piao5Songnan Zhang6Department of Oncology, Yanbian University HospitalDepartment of Oncology, Yanbian University HospitalDepartment of Oncology, Yanbian University HospitalDepartment of Oncology, Yanbian University HospitalDepartment of Oncology, Yanbian University HospitalDepartment of Radiation Oncology, Yanbian University HospitalDepartment of Oncology, Yanbian University HospitalAbstract Background Recent studies have highlighted the role of RNA modification, that is, the dysregulation of epitranscriptomics, in tumorigenesis and progression. The potential for undoing epigenetic changes may develop novel therapeutic and prognostic approaches. However, the roles of these RNA modifications in the tumor microenvironment (TME) are still unknown. Methods We assessed the expression properties and genetic alterations of 26 RNA modification writers, including adenosine-to-inosine RNA editing, alternative polyadenylation, m1A, and m6A in 502 lung adenocarcinoma (LUAD) samples from the Cancer Genome Atlas (TCGA) datasets. Then, we used differentially expressed gene (DEGs) to develop a signature for predicting patient outcomes, which was dubbed the “writer score” for RNA-modified writers. In addition, we analyzed the association between TME features, molecular subtypes, treatment sensitivity, and immunotherapy efficacy. Results We comprehensively evaluated the changes in multilayer RNA modification writers and identified the role of RNA modification writer expression imbalances in LUAD emergence and progression. Additionally, we constructed a risk-score model based on six LUAD prognosis-associated differentially expressed RNA modification writer genes. Kaplan–Meier (K–M) analyses revealed that the low risk-score signature had high overall patient survival. The predictive significance of the risk-score model was demonstrated using both univariate and multivariate Cox analyses. The risk-score model was positively correlated with the immune- and proliferation-related pathways. In response to anti-cancer treatment, high-risk score is related with high TMB, which has been discovered to correlate with immunotherapy effectiveness. Conclusion This study showed a strong correlation between the TME variety, level of complexity, and the four types of RNA modification writers. In addition, this scoring system could potentially predict effective immunotherapy and deepens our understanding of TME characteristics.https://doi.org/10.1007/s12672-025-01791-1RNA modification writerLUADRisk-scoreTMEImmunotherapy |
| spellingShingle | Qiang Xu Lingyu Kong Zhezhu Han Xiuying Jin Mingyan Ding Zhengri Piao Songnan Zhang RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma Discover Oncology RNA modification writer LUAD Risk-score TME Immunotherapy |
| title | RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma |
| title_full | RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma |
| title_fullStr | RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma |
| title_full_unstemmed | RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma |
| title_short | RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma |
| title_sort | rna modification writer based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma |
| topic | RNA modification writer LUAD Risk-score TME Immunotherapy |
| url | https://doi.org/10.1007/s12672-025-01791-1 |
| work_keys_str_mv | AT qiangxu rnamodificationwriterbasedimmunologicalprofileandgenomiclandscapeoftumormicroenvironmentinlungadenocarcinoma AT lingyukong rnamodificationwriterbasedimmunologicalprofileandgenomiclandscapeoftumormicroenvironmentinlungadenocarcinoma AT zhezhuhan rnamodificationwriterbasedimmunologicalprofileandgenomiclandscapeoftumormicroenvironmentinlungadenocarcinoma AT xiuyingjin rnamodificationwriterbasedimmunologicalprofileandgenomiclandscapeoftumormicroenvironmentinlungadenocarcinoma AT mingyanding rnamodificationwriterbasedimmunologicalprofileandgenomiclandscapeoftumormicroenvironmentinlungadenocarcinoma AT zhengripiao rnamodificationwriterbasedimmunologicalprofileandgenomiclandscapeoftumormicroenvironmentinlungadenocarcinoma AT songnanzhang rnamodificationwriterbasedimmunologicalprofileandgenomiclandscapeoftumormicroenvironmentinlungadenocarcinoma |