Intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinoma
Abstract Background Immunotherapy benefits shows discrepancy in different lung adenocarcinoma (LUAD) patients because of the intratumor heterogeneity (ITH). ITH favors tumor evolution and correlated with drug resistance. The genes mediating ITH in LUAD and their role in predicting prognosis and ther...
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Springer
2025-03-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02173-3 |
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| author | Yanhua Zuo Li Lin Libo Sun |
| author_facet | Yanhua Zuo Li Lin Libo Sun |
| author_sort | Yanhua Zuo |
| collection | DOAJ |
| description | Abstract Background Immunotherapy benefits shows discrepancy in different lung adenocarcinoma (LUAD) patients because of the intratumor heterogeneity (ITH). ITH favors tumor evolution and correlated with drug resistance. The genes mediating ITH in LUAD and their role in predicting prognosis and therapy benefits is unclear. Methods An ITH-related signature (IRS) was built by ten methods-based integrative machine learning programs using TCGA, GSE68571, GSE42127, GSE30129, GSE50081, GSE72094, GSE37745, GSE68467, and GSE31210 dataset. To assess the relationship between IRS and the tumor immune microenvironment, numerous prediction scores were employed. Results The optimal predictive signature for LUAD cases was the IRS developed using Lasso + stepCox(both) method, which had the highest average C-index of 0.80. It performed consistently and effectively in predicting the clinical outcomes of LUAD patients. Additionally, compared to the clinical stage and numerous other existing prediction models, a higher C-index was demonstrated in IRS. LUAD patients with low IRS score had a higher level of immuno-activated cells, higher TMB score, lower ITH score, higher PD1&CTLA4 immunophenoscore, and tumor escape score in LUAD. The gene set score for angiogenesis, coagulation, hypoxia, and NOTCH signaling were increased in LUAD with high IRS score. Conclusion Overall, the study developed a unique IRS for LUAD that may serve as a predictor of the clinical outcome and immunotherapy advantages for individuals with LAUD. |
| format | Article |
| id | doaj-art-b068232b60cb497faa78d224328396ef |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-b068232b60cb497faa78d224328396ef2025-08-20T03:40:45ZengSpringerDiscover Oncology2730-60112025-03-0116111110.1007/s12672-025-02173-3Intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinomaYanhua Zuo0Li Lin1Libo Sun2Department of Pharmacy, The Affiliated Hospital of Qingdao UniversityDepartment of Pharmacy, The Affiliated Hospital of Qingdao UniversityDepartment of Pharmacy, The Affiliated Hospital of Qingdao UniversityAbstract Background Immunotherapy benefits shows discrepancy in different lung adenocarcinoma (LUAD) patients because of the intratumor heterogeneity (ITH). ITH favors tumor evolution and correlated with drug resistance. The genes mediating ITH in LUAD and their role in predicting prognosis and therapy benefits is unclear. Methods An ITH-related signature (IRS) was built by ten methods-based integrative machine learning programs using TCGA, GSE68571, GSE42127, GSE30129, GSE50081, GSE72094, GSE37745, GSE68467, and GSE31210 dataset. To assess the relationship between IRS and the tumor immune microenvironment, numerous prediction scores were employed. Results The optimal predictive signature for LUAD cases was the IRS developed using Lasso + stepCox(both) method, which had the highest average C-index of 0.80. It performed consistently and effectively in predicting the clinical outcomes of LUAD patients. Additionally, compared to the clinical stage and numerous other existing prediction models, a higher C-index was demonstrated in IRS. LUAD patients with low IRS score had a higher level of immuno-activated cells, higher TMB score, lower ITH score, higher PD1&CTLA4 immunophenoscore, and tumor escape score in LUAD. The gene set score for angiogenesis, coagulation, hypoxia, and NOTCH signaling were increased in LUAD with high IRS score. Conclusion Overall, the study developed a unique IRS for LUAD that may serve as a predictor of the clinical outcome and immunotherapy advantages for individuals with LAUD.https://doi.org/10.1007/s12672-025-02173-3Intratumor heterogeneityLung adenocarcinomaBiomarkerImmunotherapyBioinformatics |
| spellingShingle | Yanhua Zuo Li Lin Libo Sun Intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinoma Discover Oncology Intratumor heterogeneity Lung adenocarcinoma Biomarker Immunotherapy Bioinformatics |
| title | Intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinoma |
| title_full | Intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinoma |
| title_fullStr | Intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinoma |
| title_full_unstemmed | Intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinoma |
| title_short | Intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinoma |
| title_sort | intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinoma |
| topic | Intratumor heterogeneity Lung adenocarcinoma Biomarker Immunotherapy Bioinformatics |
| url | https://doi.org/10.1007/s12672-025-02173-3 |
| work_keys_str_mv | AT yanhuazuo intratumorheterogeneityrelatedsignatureforclinicaloutcomeandimmunotherapyadvantagesinlungadenocarcinoma AT lilin intratumorheterogeneityrelatedsignatureforclinicaloutcomeandimmunotherapyadvantagesinlungadenocarcinoma AT libosun intratumorheterogeneityrelatedsignatureforclinicaloutcomeandimmunotherapyadvantagesinlungadenocarcinoma |