Multi-omics analyses of the heterogenous immune microenvironment in triple-negative breast cancer implicate UQCRFS1 potentiates tumor progression
Abstract Background Triple-negative breast cancer (TNBC) is commonly characterized by high-grade and aggressive features, resulting in an augmented likelihood of distant metastasis and inferior prognosis for patients. Tumor immune microenvironment (TME) has been recently considered to be tightly cor...
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BMC
2025-06-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s40164-025-00672-1 |
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| author | Yuhui Tang Aiqi Xu Zhongbiao Xu Jindong Xie Wei Huang Liulu Zhang Yitian Chen Lu Yang Shasha Du Kun Wang |
| author_facet | Yuhui Tang Aiqi Xu Zhongbiao Xu Jindong Xie Wei Huang Liulu Zhang Yitian Chen Lu Yang Shasha Du Kun Wang |
| author_sort | Yuhui Tang |
| collection | DOAJ |
| description | Abstract Background Triple-negative breast cancer (TNBC) is commonly characterized by high-grade and aggressive features, resulting in an augmented likelihood of distant metastasis and inferior prognosis for patients. Tumor immune microenvironment (TME) has been recently considered to be tightly correlated with tumor progression and immunotherapy response. However, the actual heterogenous TME within TNBC remains more explorations. Methods The thorough analyses of different cell types within TME were conducted on the self-tested single-cell RNA sequencing dataset which contained nine TNBC treatment-naïve patients, including subclusters classification, CellChat algorithm, transcription factors (TFs) expression, pseudotime analysis and functional enrichment assay. The malignant epithelial cluster was confirmed by copy number variations analysis, and subsequently LASSO-Cox regression was carried out to establish a Malignant Cell Index (MCI) model on the basis of five crucial genes (BGN, SDC1, IMPDH2, SPINT1, and UQCRFS1), which was validated in several TNBC cohorts through Kaplan–Meier survival and immunotherapy response analyses. The public spatial transcriptome, proteome data and qRT-PCR, western blotting experiments were exploited to corroborate UQCRFS1 expression in RNA and protein levels. Additionally, functional experiments were implemented to unravel the impacts of UQCRFS1 on TNBC cells. Results The diverse subclusters of TME cells within TNBC were clarified to display distinct characteristics in cell–cell interactions, TFs expression, differentiation trajectory and functional pathways. Particularly, IL32high Treg imparted an essential effect on tumor evasion and predicted a worsened prognosis of TNBC patients. Furthermore, MCI model enabled to notify the inferior prognosis and immunotherapy resistance in TNBC. Ultimately, UQCRFS1 knockdown dampened the proliferative and migratory competence in vitro as well as tumor growth in vivo of TNBC cells. Conclusions Our study offers innovative perspectives on comprehending the heterogeneity within TME of TNBC, thereby facilitating the elucidation of TNBC biology and providing clinical recommendations for TNBC patients' prognosis, such as IL32high Treg infiltration, MCI evaluation, and UQCRFS1 expression. |
| format | Article |
| id | doaj-art-e3a955f3c2154b19bca0acf91e217833 |
| institution | OA Journals |
| issn | 2162-3619 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj-art-e3a955f3c2154b19bca0acf91e2178332025-08-20T02:37:57ZengBMCExperimental Hematology & Oncology2162-36192025-06-0114112310.1186/s40164-025-00672-1Multi-omics analyses of the heterogenous immune microenvironment in triple-negative breast cancer implicate UQCRFS1 potentiates tumor progressionYuhui Tang0Aiqi Xu1Zhongbiao Xu2Jindong Xie3Wei Huang4Liulu Zhang5Yitian Chen6Lu Yang7Shasha Du8Kun Wang9State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Radiotherapy, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Radiotherapy, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Radiotherapy, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Radiotherapy, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityAbstract Background Triple-negative breast cancer (TNBC) is commonly characterized by high-grade and aggressive features, resulting in an augmented likelihood of distant metastasis and inferior prognosis for patients. Tumor immune microenvironment (TME) has been recently considered to be tightly correlated with tumor progression and immunotherapy response. However, the actual heterogenous TME within TNBC remains more explorations. Methods The thorough analyses of different cell types within TME were conducted on the self-tested single-cell RNA sequencing dataset which contained nine TNBC treatment-naïve patients, including subclusters classification, CellChat algorithm, transcription factors (TFs) expression, pseudotime analysis and functional enrichment assay. The malignant epithelial cluster was confirmed by copy number variations analysis, and subsequently LASSO-Cox regression was carried out to establish a Malignant Cell Index (MCI) model on the basis of five crucial genes (BGN, SDC1, IMPDH2, SPINT1, and UQCRFS1), which was validated in several TNBC cohorts through Kaplan–Meier survival and immunotherapy response analyses. The public spatial transcriptome, proteome data and qRT-PCR, western blotting experiments were exploited to corroborate UQCRFS1 expression in RNA and protein levels. Additionally, functional experiments were implemented to unravel the impacts of UQCRFS1 on TNBC cells. Results The diverse subclusters of TME cells within TNBC were clarified to display distinct characteristics in cell–cell interactions, TFs expression, differentiation trajectory and functional pathways. Particularly, IL32high Treg imparted an essential effect on tumor evasion and predicted a worsened prognosis of TNBC patients. Furthermore, MCI model enabled to notify the inferior prognosis and immunotherapy resistance in TNBC. Ultimately, UQCRFS1 knockdown dampened the proliferative and migratory competence in vitro as well as tumor growth in vivo of TNBC cells. Conclusions Our study offers innovative perspectives on comprehending the heterogeneity within TME of TNBC, thereby facilitating the elucidation of TNBC biology and providing clinical recommendations for TNBC patients' prognosis, such as IL32high Treg infiltration, MCI evaluation, and UQCRFS1 expression.https://doi.org/10.1186/s40164-025-00672-1Triple-negative breast cancerMulti-omicsTumor immune microenvironmentIL32high TregUQCRFS1Immunotherapy resistance |
| spellingShingle | Yuhui Tang Aiqi Xu Zhongbiao Xu Jindong Xie Wei Huang Liulu Zhang Yitian Chen Lu Yang Shasha Du Kun Wang Multi-omics analyses of the heterogenous immune microenvironment in triple-negative breast cancer implicate UQCRFS1 potentiates tumor progression Experimental Hematology & Oncology Triple-negative breast cancer Multi-omics Tumor immune microenvironment IL32high Treg UQCRFS1 Immunotherapy resistance |
| title | Multi-omics analyses of the heterogenous immune microenvironment in triple-negative breast cancer implicate UQCRFS1 potentiates tumor progression |
| title_full | Multi-omics analyses of the heterogenous immune microenvironment in triple-negative breast cancer implicate UQCRFS1 potentiates tumor progression |
| title_fullStr | Multi-omics analyses of the heterogenous immune microenvironment in triple-negative breast cancer implicate UQCRFS1 potentiates tumor progression |
| title_full_unstemmed | Multi-omics analyses of the heterogenous immune microenvironment in triple-negative breast cancer implicate UQCRFS1 potentiates tumor progression |
| title_short | Multi-omics analyses of the heterogenous immune microenvironment in triple-negative breast cancer implicate UQCRFS1 potentiates tumor progression |
| title_sort | multi omics analyses of the heterogenous immune microenvironment in triple negative breast cancer implicate uqcrfs1 potentiates tumor progression |
| topic | Triple-negative breast cancer Multi-omics Tumor immune microenvironment IL32high Treg UQCRFS1 Immunotherapy resistance |
| url | https://doi.org/10.1186/s40164-025-00672-1 |
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