A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer
We generated a 4-gene score with genes upregulated in LM2-4, a metastatic variant of MDA-MB-231 (DOK 4, HCCS, PGF, and SHCBP1) that was strongly associated with disease-free survival (DFS) in TCGA cohort (hazard ratio [HR]>1.2, <i>p</i> < 0.02). The 4-gene score correlated with ove...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/5/1148 |
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| author | Masanori Oshi Eriko Katsuta Li Yan John M.L. Ebos Omar M. Rashid Ryusei Matsuyama Itaru Endo Kazuaki Takabe |
| author_facet | Masanori Oshi Eriko Katsuta Li Yan John M.L. Ebos Omar M. Rashid Ryusei Matsuyama Itaru Endo Kazuaki Takabe |
| author_sort | Masanori Oshi |
| collection | DOAJ |
| description | We generated a 4-gene score with genes upregulated in LM2-4, a metastatic variant of MDA-MB-231 (DOK 4, HCCS, PGF, and SHCBP1) that was strongly associated with disease-free survival (DFS) in TCGA cohort (hazard ratio [HR]>1.2, <i>p</i> < 0.02). The 4-gene score correlated with overall survival of TCGA (HR = 1.44, <i>p</i> < 0.001), which was validated with DFS and disease-specific survival of METABRIC cohort. The 4-gene score was able to predict worse survival or clinically aggressive tumors, such as high Nottingham pathological grade and advanced cancer staging. High score was associated with worse survival in the hormonal receptor (HR)-positive/Her2-negative subtype. High score enriched cell proliferation-related gene sets in GSEA. The score was high in primary tumors that originated, in and metastasized to, brain and lung, and it predicted worse progression-free survival for metastatic tumors. Good tumor response to neoadjuvant chemotherapy or hormonal therapy was accompanied by score reduction. High scores were also predictive of response to neoadjuvant chemotherapy for HR-positive/Her2-negative subtype. High score tumors had increased expression of T cell exhaustion marker genes, suggesting that the score may also be a biomarker for immunotherapy response. Our novel 4-gene score with both prognostic and predictive values may, therefore, be clinically useful particularly in HR-positive breast cancer. |
| first_indexed | 2024-03-10T20:03:35Z |
| format | Article |
| id | doaj.art-6f99bdfc9f234e40883aefb70a2dbec4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:03:35Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6f99bdfc9f234e40883aefb70a2dbec42023-11-19T23:23:37ZengMDPI AGCancers2072-66942020-05-01125114810.3390/cancers12051148A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast CancerMasanori Oshi0Eriko Katsuta1Li Yan2John M.L. Ebos3Omar M. Rashid4Ryusei Matsuyama5Itaru Endo6Kazuaki Takabe7Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Surgery, Holy Cross Hospital, Michael and Dianne Bienes Comprehensive Cancer Center, Fort Lauderdale, FL 33308, USADepartment of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, JapanDepartment of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, JapanDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USAWe generated a 4-gene score with genes upregulated in LM2-4, a metastatic variant of MDA-MB-231 (DOK 4, HCCS, PGF, and SHCBP1) that was strongly associated with disease-free survival (DFS) in TCGA cohort (hazard ratio [HR]>1.2, <i>p</i> < 0.02). The 4-gene score correlated with overall survival of TCGA (HR = 1.44, <i>p</i> < 0.001), which was validated with DFS and disease-specific survival of METABRIC cohort. The 4-gene score was able to predict worse survival or clinically aggressive tumors, such as high Nottingham pathological grade and advanced cancer staging. High score was associated with worse survival in the hormonal receptor (HR)-positive/Her2-negative subtype. High score enriched cell proliferation-related gene sets in GSEA. The score was high in primary tumors that originated, in and metastasized to, brain and lung, and it predicted worse progression-free survival for metastatic tumors. Good tumor response to neoadjuvant chemotherapy or hormonal therapy was accompanied by score reduction. High scores were also predictive of response to neoadjuvant chemotherapy for HR-positive/Her2-negative subtype. High score tumors had increased expression of T cell exhaustion marker genes, suggesting that the score may also be a biomarker for immunotherapy response. Our novel 4-gene score with both prognostic and predictive values may, therefore, be clinically useful particularly in HR-positive breast cancer.https://www.mdpi.com/2072-6694/12/5/1148biomarkerbreast cancergene expressionmetastasisprognosistreatment response |
| spellingShingle | Masanori Oshi Eriko Katsuta Li Yan John M.L. Ebos Omar M. Rashid Ryusei Matsuyama Itaru Endo Kazuaki Takabe A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer Cancers biomarker breast cancer gene expression metastasis prognosis treatment response |
| title | A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer |
| title_full | A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer |
| title_fullStr | A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer |
| title_full_unstemmed | A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer |
| title_short | A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer |
| title_sort | novel 4 gene score to predict survival distant metastasis and response to neoadjuvant therapy in breast cancer |
| topic | biomarker breast cancer gene expression metastasis prognosis treatment response |
| url | https://www.mdpi.com/2072-6694/12/5/1148 |
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