Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation
BackgroundTumor budding (TB) is emerging as a prognostic factor in multiple cancers. Likewise, the stemness of cancer cells also plays a vital role in cancer progression. However, nearly no research has focused on the interaction of TB and tumor stemness in cancer.MethodsTissue microarrays including...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.818869/full |
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| author | Zhenxian Xiang Zhenxian Xiang Zhenxian Xiang Zhenxian Xiang Qiuming He Qiuming He Qiuming He Qiuming He Li Huang Bin Xiong Bin Xiong Bin Xiong Bin Xiong Qingming Xiang Qingming Xiang Qingming Xiang |
| author_facet | Zhenxian Xiang Zhenxian Xiang Zhenxian Xiang Zhenxian Xiang Qiuming He Qiuming He Qiuming He Qiuming He Li Huang Bin Xiong Bin Xiong Bin Xiong Bin Xiong Qingming Xiang Qingming Xiang Qingming Xiang |
| author_sort | Zhenxian Xiang |
| collection | DOAJ |
| description | BackgroundTumor budding (TB) is emerging as a prognostic factor in multiple cancers. Likewise, the stemness of cancer cells also plays a vital role in cancer progression. However, nearly no research has focused on the interaction of TB and tumor stemness in cancer.MethodsTissue microarrays including 229 cases of invasive breast cancer (BC) were established and subjected to pan-cytokeratin immunohistochemical staining to evaluate molecular expression. Univariate and multivariate analyses were applied to identify prognostic factors of BC, and the Chi-square test was used for comparison of categorical variables.ResultsHigh-grade TB was significantly associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, epithelial-mesenchymal transition, and poor disease-free survival (DFS) of BC patients. We also found that the prognostic value of TB varied widely among different subtypes and subgroups. Cox regression analysis then showed that TB grade was an independent prognostic factor. Moreover, cancer stem cell (CSC) markers CD44 and ALDH1A1 were significantly higher in high-grade TB tumors. Consequently, patients were classified into high CSC score subgroup and low CSC score subgroups. Further research found that CSC scores correlated with clinicopathological features and DFS of BC patients. Based on TB grade and CSC scores, we classified BC patients into TBlow-CSCslow (type I), TBlow-CSCshigh (type II), TBhigh-CSCslow (type III), and TBhigh-CSCshigh (type IV) subgroups. Survival analysis showed that patients in the type I subgroup had the best DFS, whereas those in the type IV subgroup had the worst DFS. Finally, a TB-CSC-based nomogram for use in BC was established. The nomogram was well calibrated to predict the probability of 5-year DFS, and the C-index was 0.837. Finally, the area under the curve value for the nomogram (0.892) was higher than that of the TNM staging system (0.713).ConclusionThe combination of TB grade with CSC score improves the prognostic evaluation of BC patients. A novel nomogram containing TB grade and CSC score provides doctors with a candidate tool to guide the individualized treatment of cancer patients. |
| first_indexed | 2024-04-11T20:42:38Z |
| format | Article |
| id | doaj.art-7fdccea594e249c894ecc6b3c9032022 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T20:42:38Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-7fdccea594e249c894ecc6b3c90320222022-12-22T04:04:09ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011110.3389/fonc.2021.818869818869Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis EvaluationZhenxian Xiang0Zhenxian Xiang1Zhenxian Xiang2Zhenxian Xiang3Qiuming He4Qiuming He5Qiuming He6Qiuming He7Li Huang8Bin Xiong9Bin Xiong10Bin Xiong11Bin Xiong12Qingming Xiang13Qingming Xiang14Qingming Xiang15Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, ChinaBackgroundTumor budding (TB) is emerging as a prognostic factor in multiple cancers. Likewise, the stemness of cancer cells also plays a vital role in cancer progression. However, nearly no research has focused on the interaction of TB and tumor stemness in cancer.MethodsTissue microarrays including 229 cases of invasive breast cancer (BC) were established and subjected to pan-cytokeratin immunohistochemical staining to evaluate molecular expression. Univariate and multivariate analyses were applied to identify prognostic factors of BC, and the Chi-square test was used for comparison of categorical variables.ResultsHigh-grade TB was significantly associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, epithelial-mesenchymal transition, and poor disease-free survival (DFS) of BC patients. We also found that the prognostic value of TB varied widely among different subtypes and subgroups. Cox regression analysis then showed that TB grade was an independent prognostic factor. Moreover, cancer stem cell (CSC) markers CD44 and ALDH1A1 were significantly higher in high-grade TB tumors. Consequently, patients were classified into high CSC score subgroup and low CSC score subgroups. Further research found that CSC scores correlated with clinicopathological features and DFS of BC patients. Based on TB grade and CSC scores, we classified BC patients into TBlow-CSCslow (type I), TBlow-CSCshigh (type II), TBhigh-CSCslow (type III), and TBhigh-CSCshigh (type IV) subgroups. Survival analysis showed that patients in the type I subgroup had the best DFS, whereas those in the type IV subgroup had the worst DFS. Finally, a TB-CSC-based nomogram for use in BC was established. The nomogram was well calibrated to predict the probability of 5-year DFS, and the C-index was 0.837. Finally, the area under the curve value for the nomogram (0.892) was higher than that of the TNM staging system (0.713).ConclusionThe combination of TB grade with CSC score improves the prognostic evaluation of BC patients. A novel nomogram containing TB grade and CSC score provides doctors with a candidate tool to guide the individualized treatment of cancer patients.https://www.frontiersin.org/articles/10.3389/fonc.2021.818869/fullCSCsALDH1A1CD24CD44breast cancertumor budding |
| spellingShingle | Zhenxian Xiang Zhenxian Xiang Zhenxian Xiang Zhenxian Xiang Qiuming He Qiuming He Qiuming He Qiuming He Li Huang Bin Xiong Bin Xiong Bin Xiong Bin Xiong Qingming Xiang Qingming Xiang Qingming Xiang Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation Frontiers in Oncology CSCs ALDH1A1 CD24 CD44 breast cancer tumor budding |
| title | Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation |
| title_full | Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation |
| title_fullStr | Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation |
| title_full_unstemmed | Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation |
| title_short | Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation |
| title_sort | breast cancer classification based on tumor budding and stem cell related signatures facilitate prognosis evaluation |
| topic | CSCs ALDH1A1 CD24 CD44 breast cancer tumor budding |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.818869/full |
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