The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients
Abstract Objective Although the tumor mutation burden (TMB) was reported as a biomarker for immunotherapy of various cancers, whether it can effectively predict the survival prognosis in breast cancer patients remains unclear. In this study, the prognostic value of TMB and its correlation with immun...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-02-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-023-01058-x |
| _version_ | 1797865176891916288 |
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| author | Shengjin Cui Jingying Feng Xi Tang Shuang Lou Weiquan Guo Xiaowei Xiao Shuping Li Xue Chen Yu Huan Yiwen Zhou Lijia Xiao |
| author_facet | Shengjin Cui Jingying Feng Xi Tang Shuang Lou Weiquan Guo Xiaowei Xiao Shuping Li Xue Chen Yu Huan Yiwen Zhou Lijia Xiao |
| author_sort | Shengjin Cui |
| collection | DOAJ |
| description | Abstract Objective Although the tumor mutation burden (TMB) was reported as a biomarker for immunotherapy of various cancers, whether it can effectively predict the survival prognosis in breast cancer patients remains unclear. In this study, the prognostic value of TMB and its correlation with immune infiltration were explored by using multigroup studies. Methods The somatic mutation data of 986 breast cancer patients were obtained from TCGA database. Breast cancer patients were divided into a low-TMB group and a high-TMB group according to the quartile of TMB scores. The differentially expressed genes (DEGs) were identified by the “limma” R program. The CIBERSORT algorithm was utilized to estimate the immune cell fraction of each sample. The TIMER database was utilized to evaluate the association between CNVs of immune genes and tumor immune cell infiltration and the prognostic value of the immune cells in breast cancer. Results In breast cancer, TP53, PIK3CA, TTN, CDH1 and other genes were the most important mutated genes. Higher survival rate of patients was found in the low-TMB group. Among the top 10 DEGs, three of them belong to the KRT gene family. GSEA enrichment analysis showed that MAPK, Hedgehog, mTOR, TGF-bate and GnRH signaling pathways were enriched in the low-TMB group. The infiltration levels of the most of immune cells were higher in the low-TMB group (P < 0.01). Higher expression of CCL18 and TRGC1 was correlated with poor prognosis. Breast cancer patients with CCL18 copy number variations, especially arm-level gains, showed significantly decreased immune cell infiltration. In the low B cell infiltration group, the survival prognosis of breast cancer patients was poor. Conclusions TMB is a potential prognosis marker in breast cancer. Immune-related gene CCL18 and TRGC1 are biomarkers of poor prognosis while immune (B cell) infiltration is a biomarker of good prognosis. |
| first_indexed | 2024-04-09T23:04:55Z |
| format | Article |
| id | doaj.art-2541eaf152f24045bfda59ba28d2578e |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-04-09T23:04:55Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-2541eaf152f24045bfda59ba28d2578e2023-03-22T10:46:29ZengBMCEuropean Journal of Medical Research2047-783X2023-02-0128111110.1186/s40001-023-01058-xThe prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patientsShengjin Cui0Jingying Feng1Xi Tang2Shuang Lou3Weiquan Guo4Xiaowei Xiao5Shuping Li6Xue Chen7Yu Huan8Yiwen Zhou9Lijia Xiao10Department of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityDepartment of Clinical Laboratory, Shenzhen Hospital, Southern Medical UniversityAbstract Objective Although the tumor mutation burden (TMB) was reported as a biomarker for immunotherapy of various cancers, whether it can effectively predict the survival prognosis in breast cancer patients remains unclear. In this study, the prognostic value of TMB and its correlation with immune infiltration were explored by using multigroup studies. Methods The somatic mutation data of 986 breast cancer patients were obtained from TCGA database. Breast cancer patients were divided into a low-TMB group and a high-TMB group according to the quartile of TMB scores. The differentially expressed genes (DEGs) were identified by the “limma” R program. The CIBERSORT algorithm was utilized to estimate the immune cell fraction of each sample. The TIMER database was utilized to evaluate the association between CNVs of immune genes and tumor immune cell infiltration and the prognostic value of the immune cells in breast cancer. Results In breast cancer, TP53, PIK3CA, TTN, CDH1 and other genes were the most important mutated genes. Higher survival rate of patients was found in the low-TMB group. Among the top 10 DEGs, three of them belong to the KRT gene family. GSEA enrichment analysis showed that MAPK, Hedgehog, mTOR, TGF-bate and GnRH signaling pathways were enriched in the low-TMB group. The infiltration levels of the most of immune cells were higher in the low-TMB group (P < 0.01). Higher expression of CCL18 and TRGC1 was correlated with poor prognosis. Breast cancer patients with CCL18 copy number variations, especially arm-level gains, showed significantly decreased immune cell infiltration. In the low B cell infiltration group, the survival prognosis of breast cancer patients was poor. Conclusions TMB is a potential prognosis marker in breast cancer. Immune-related gene CCL18 and TRGC1 are biomarkers of poor prognosis while immune (B cell) infiltration is a biomarker of good prognosis.https://doi.org/10.1186/s40001-023-01058-xBreast cancerTumor mutation burden (TMB)Immune infiltrateSurvival |
| spellingShingle | Shengjin Cui Jingying Feng Xi Tang Shuang Lou Weiquan Guo Xiaowei Xiao Shuping Li Xue Chen Yu Huan Yiwen Zhou Lijia Xiao The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients European Journal of Medical Research Breast cancer Tumor mutation burden (TMB) Immune infiltrate Survival |
| title | The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients |
| title_full | The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients |
| title_fullStr | The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients |
| title_full_unstemmed | The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients |
| title_short | The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients |
| title_sort | prognostic value of tumor mutation burden tmb and its relationship with immune infiltration in breast cancer patients |
| topic | Breast cancer Tumor mutation burden (TMB) Immune infiltrate Survival |
| url | https://doi.org/10.1186/s40001-023-01058-x |
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