Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancer
Abstract Background Triple-negative breast cancer (TNBC) is the most heterogenous and aggressive subtype of breast cancer. Chemotherapy remains the standard treatment option for patients with TNBC owing to the unavailability of acceptable targets and biomarkers in clinical practice. Novel biomarkers...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | World Journal of Surgical Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12957-023-03078-7 |
| _version_ | 1797789677597491200 |
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| author | Xuanzhao Chen Zeyan Li Meihua Liang Ziyang Zhang Di Zhu Biyun Lin Renyu Zhou Yuanzhi Lu |
| author_facet | Xuanzhao Chen Zeyan Li Meihua Liang Ziyang Zhang Di Zhu Biyun Lin Renyu Zhou Yuanzhi Lu |
| author_sort | Xuanzhao Chen |
| collection | DOAJ |
| description | Abstract Background Triple-negative breast cancer (TNBC) is the most heterogenous and aggressive subtype of breast cancer. Chemotherapy remains the standard treatment option for patients with TNBC owing to the unavailability of acceptable targets and biomarkers in clinical practice. Novel biomarkers and targets for patient stratification and treatment of TNBC are urgently needed. It has been reported that the overexpression of DNA damage-inducible transcript 4 gene (DDIT4) is associated with resistance to neoadjuvant chemotherapy and poor prognosis in patients with TNBC. In this study, we aimed to identify novel biomarkers and therapeutic targets using RNA sequencing (RNA-seq) and data mining using data from public databases. Methods RNA sequencing (RNA-Seq) was performed to detect the different gene expression patterns in the human TNBC cell line HS578T treated with docetaxel or doxorubicin. Sequencing data were further analyzed by the R package “edgeR” and “clusterProfiler” to identify the profile of differentially expressed genes (DEGs) and annotate gene functions. The prognostic and predictive value of DDIT4 expression in patients with TNBC was further validated by published online data resources, including TIMER, UALCAN, Kaplan–Meier plotter, and LinkedOmics, and GeneMANIA and GSCALite were used to investigate the functional networks and hub genes related to DDIT4, respectively. Results Through the integrative analyses of RNA-Seq data and public datasets, we observed the overexpression of DDIT4 in TNBC tissues and found that patients with DDIT4 overexpression showed poor survival outcomes. Notably, immune infiltration analysis showed that the levels of DDIT4 expression correlated negatively with the abundance of tumor-infiltrating immune cells and immune biomarker expression, but correlated positively with immune checkpoint molecules. Furthermore, DDIT4 and its hub genes (ADM, ENO1, PLOD1, and CEBPB) involved in the activation of apoptosis, cell cycle, and EMT pathways. Eventually, we found ADM, ENO1, PLOD1, and CEBPB showed poor overall survival in BC patients. Conclusion In this study, we found that DDIT4 expression is associated with the progression, therapeutic efficacy, and immune microenvironment of patients with TNBC, and DDIT4 would be as a potential prognostic biomarker and therapeutic target. These findings will help to identify potential molecular targets and improve therapeutic strategies against TNBC. |
| first_indexed | 2024-03-13T01:54:04Z |
| format | Article |
| id | doaj.art-003486bd6477485aa5e1f4d2f2bb0677 |
| institution | Directory Open Access Journal |
| issn | 1477-7819 |
| language | English |
| last_indexed | 2024-03-13T01:54:04Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | World Journal of Surgical Oncology |
| spelling | doaj.art-003486bd6477485aa5e1f4d2f2bb06772023-07-02T11:17:47ZengBMCWorld Journal of Surgical Oncology1477-78192023-06-0121111810.1186/s12957-023-03078-7Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancerXuanzhao Chen0Zeyan Li1Meihua Liang2Ziyang Zhang3Di Zhu4Biyun Lin5Renyu Zhou6Yuanzhi Lu7The Center of Pathological Diagnosis and Research, Affiliated Hospital of Guangdong Medical UniversityRenmin Hospital of Wuhan UniversityThe Center of Pathological Diagnosis and Research, Affiliated Hospital of Guangdong Medical UniversityGuangzhou Huayin Medical Laboratory Center, Ltd.Department of Clinical Pathology, First Affiliated Hospital of Jinan UniversityThe Center of Pathological Diagnosis and Research, Affiliated Hospital of Guangdong Medical UniversitySchool of Medicine, Jinan UniversityThe Center of Pathological Diagnosis and Research, Affiliated Hospital of Guangdong Medical UniversityAbstract Background Triple-negative breast cancer (TNBC) is the most heterogenous and aggressive subtype of breast cancer. Chemotherapy remains the standard treatment option for patients with TNBC owing to the unavailability of acceptable targets and biomarkers in clinical practice. Novel biomarkers and targets for patient stratification and treatment of TNBC are urgently needed. It has been reported that the overexpression of DNA damage-inducible transcript 4 gene (DDIT4) is associated with resistance to neoadjuvant chemotherapy and poor prognosis in patients with TNBC. In this study, we aimed to identify novel biomarkers and therapeutic targets using RNA sequencing (RNA-seq) and data mining using data from public databases. Methods RNA sequencing (RNA-Seq) was performed to detect the different gene expression patterns in the human TNBC cell line HS578T treated with docetaxel or doxorubicin. Sequencing data were further analyzed by the R package “edgeR” and “clusterProfiler” to identify the profile of differentially expressed genes (DEGs) and annotate gene functions. The prognostic and predictive value of DDIT4 expression in patients with TNBC was further validated by published online data resources, including TIMER, UALCAN, Kaplan–Meier plotter, and LinkedOmics, and GeneMANIA and GSCALite were used to investigate the functional networks and hub genes related to DDIT4, respectively. Results Through the integrative analyses of RNA-Seq data and public datasets, we observed the overexpression of DDIT4 in TNBC tissues and found that patients with DDIT4 overexpression showed poor survival outcomes. Notably, immune infiltration analysis showed that the levels of DDIT4 expression correlated negatively with the abundance of tumor-infiltrating immune cells and immune biomarker expression, but correlated positively with immune checkpoint molecules. Furthermore, DDIT4 and its hub genes (ADM, ENO1, PLOD1, and CEBPB) involved in the activation of apoptosis, cell cycle, and EMT pathways. Eventually, we found ADM, ENO1, PLOD1, and CEBPB showed poor overall survival in BC patients. Conclusion In this study, we found that DDIT4 expression is associated with the progression, therapeutic efficacy, and immune microenvironment of patients with TNBC, and DDIT4 would be as a potential prognostic biomarker and therapeutic target. These findings will help to identify potential molecular targets and improve therapeutic strategies against TNBC.https://doi.org/10.1186/s12957-023-03078-7TNBCBioinformaticsPrognosisTargeting therapyImmune microenvironment |
| spellingShingle | Xuanzhao Chen Zeyan Li Meihua Liang Ziyang Zhang Di Zhu Biyun Lin Renyu Zhou Yuanzhi Lu Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancer World Journal of Surgical Oncology TNBC Bioinformatics Prognosis Targeting therapy Immune microenvironment |
| title | Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancer |
| title_full | Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancer |
| title_fullStr | Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancer |
| title_full_unstemmed | Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancer |
| title_short | Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancer |
| title_sort | identification of ddit4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple negative breast cancer |
| topic | TNBC Bioinformatics Prognosis Targeting therapy Immune microenvironment |
| url | https://doi.org/10.1186/s12957-023-03078-7 |
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