Exploration of the breast ductal carcinoma in situ signature and its prognostic implications

Abstract Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%–50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is esse...

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Main Authors: Jiao Zhang, Hui Lin, Lei Hou, Hui Xiao, Xilong Gong, Xuhui Guo, Xuchen Cao, Zhenzhen Liu
Format: Article
Language:English
Published: Wiley 2023-02-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.5071
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author Jiao Zhang
Hui Lin
Lei Hou
Hui Xiao
Xilong Gong
Xuhui Guo
Xuchen Cao
Zhenzhen Liu
author_facet Jiao Zhang
Hui Lin
Lei Hou
Hui Xiao
Xilong Gong
Xuhui Guo
Xuchen Cao
Zhenzhen Liu
author_sort Jiao Zhang
collection DOAJ
description Abstract Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%–50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time‐dependent receiver operating characteristic (ROC), Kaplan–Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein–protein interaction). A unique six‐gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision‐making for individual care.
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spelling doaj-art-95041b7a0cb34b92bc8e6e11880a7d992025-08-20T01:53:22ZengWileyCancer Medicine2045-76342023-02-011233758377210.1002/cam4.5071Exploration of the breast ductal carcinoma in situ signature and its prognostic implicationsJiao Zhang0Hui Lin1Lei Hou2Hui Xiao3Xilong Gong4Xuhui Guo5Xuchen Cao6Zhenzhen Liu7Department of Breast Disease, Henan Breast Cancer Center Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital Zhengzhou ChinaThe First Department of Breast Cancer Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education Tianjin ChinaDepartment of Breast Disease, Henan Breast Cancer Center Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital Zhengzhou ChinaDepartment of Breast Disease, Henan Breast Cancer Center Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital Zhengzhou ChinaDepartment of Breast Disease, Henan Breast Cancer Center Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital Zhengzhou ChinaDepartment of Breast Disease, Henan Breast Cancer Center Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital Zhengzhou ChinaThe First Department of Breast Cancer Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education Tianjin ChinaDepartment of Breast Disease, Henan Breast Cancer Center Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital Zhengzhou ChinaAbstract Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%–50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time‐dependent receiver operating characteristic (ROC), Kaplan–Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein–protein interaction). A unique six‐gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision‐making for individual care.https://doi.org/10.1002/cam4.5071biomarkerductal carcinoma in situgene signatureprognosis
spellingShingle Jiao Zhang
Hui Lin
Lei Hou
Hui Xiao
Xilong Gong
Xuhui Guo
Xuchen Cao
Zhenzhen Liu
Exploration of the breast ductal carcinoma in situ signature and its prognostic implications
Cancer Medicine
biomarker
ductal carcinoma in situ
gene signature
prognosis
title Exploration of the breast ductal carcinoma in situ signature and its prognostic implications
title_full Exploration of the breast ductal carcinoma in situ signature and its prognostic implications
title_fullStr Exploration of the breast ductal carcinoma in situ signature and its prognostic implications
title_full_unstemmed Exploration of the breast ductal carcinoma in situ signature and its prognostic implications
title_short Exploration of the breast ductal carcinoma in situ signature and its prognostic implications
title_sort exploration of the breast ductal carcinoma in situ signature and its prognostic implications
topic biomarker
ductal carcinoma in situ
gene signature
prognosis
url https://doi.org/10.1002/cam4.5071
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