Dataset Information

Clinicopathologic and Prognostic Significance of the Zinc Finger of the Cerebellum Family in Invasive Breast Cancer.

ABSTRACT:

Purpose

Five members of the zinc finger of the cerebellum (ZIC) family-ZIC1, ZIC2, ZIC3, ZIC4, and ZIC5-have been shown to be involved in various carcinomas. Here, we aimed to explore the clinicopathologic and prognostic roles of ZIC family members in invasive breast cancer patients using immunohistochemical analysis, western blotting analysis, and real-time quantitative polymerase chain reaction (RT-qPCR).

Methods

A total of 241 female invasive breast cancer patients who underwent radical mastectomy between 2009 and 2011 were enrolled. ZIC proteins in 241 pairs of breast tumors and corresponding normal tissues were investigated using immunohistochemistry and the clinicopathologic roles of proteins were analyzed using Pearson's chi-square test. Kaplan-Meier curves and Cox regression analysis were also used to analyze the prognostic value of the ZIC proteins. In addition, 12 pairs of fresh-frozen breast tumors and matched normal tissues were used in the western blotting analysis and RT-qPCR.

Results

Only ZIC1 expression in normal tissues was obviously higher than that in tumors (p<0.001). On multivariate analysis, ZIC1 expression (in overall survival analysis: hazard ratio [HR], 0.405, 95% confidence interval [CI], 0.233-0.702, p=0.001; in disease-free survival analysis: HR, 0.395, 95% CI, 0.234-0.669, p=0.001) was identified as a prognostic indicator of invasive breast cancer.

Conclusion

ZIC1, but not the other proteins, was obviously decreased in breast tumors and associated with clinicopathologic factors. Thus, ZIC1 might be a novel indicator to predict the overall and disease-free survival of invasive breast cancer patients.

SUBMITTER: Han W

PROVIDER: S-EPMC5880966 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Clinicopathologic and Prognostic Significance of the Zinc Finger of the Cerebellum Family in Invasive Breast Cancer.

Han Wei W Zhang Cong C Gao Xiao-Jiao XJ Wang Hua-Bing HB Chen Fang F Cao Fang F Hu Yong-Wei YW Ma Jun J Gu Xing X Ding Hou-Zhong HZ

Journal of breast cancer 20180323 1

<h4>Purpose</h4>Five members of the zinc finger of the cerebellum (ZIC) family-ZIC1, ZIC2, ZIC3, ZIC4, and ZIC5-have been shown to be involved in various carcinomas. Here, we aimed to explore the clinicopathologic and prognostic roles of ZIC family members in invasive breast cancer patients using immunohistochemical analysis, western blotting analysis, and real-time quantitative polymerase chain reaction (RT-qPCR).<h4>Methods</h4>A total of 241 female invasive breast cancer patients who underwen ...[more]

PMID: 29628984

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Project description:BackgroundBreast invasive carcinoma (BRCA) is a commonly occurring malignant tumor. Zinc finger proteins (ZNFs) constitute the largest transcription factor family in the human genome and play a mechanistic role in many cancers' development. The prognostic value of ZNFs has yet to be approached systematically for BRCA.MethodsWe analyzed the data of a training set from The Cancer Genome Atlas (TCGA) database and two validation cohort from GSE20685 and METABRIC datasets, composed of 3,231 BRCA patients. After screening the differentially expressed ZNFs, univariate Cox regression, LASSO, and multiple Cox regression analysis were performed to construct a risk-based predictive model. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and gene set enrichment analyses (GSEA) were utilized to assess the potential relations among the tumor immune microenvironment and ZNFs in BRCA.ResultsIn this study, we profiled ZNF expression in TCGA based BRCA cohort and developed a novel prognostic model based on 14 genes with ZNF relations. This model was composed of high and low-score groups for BRCA classification. Based upon Kaplan-Meier survival curves, risk-status-based prognosis illustrated significant differences. We integrated the 14 ZNF-gene signature with patient clinicopathological data for nomogram construction with accurate 1-, 3-, and 5-overall survival predictive capabilities. We then accessed the Genomics of Drug Sensitivity in Cancer database for therapeutic drug response prediction of signature-defined BRCA patient groupings for our selected TCGA population. The signature also predicts sensitivity to chemotherapeutic and molecular-targeted agents in high- and low-risk patients afflicted with BRCA. Functional analysis suggested JAK STAT, VEGF, MAPK, NOTCH TOLL-like receptor, NOD-like receptor signaling pathways, apoptosis, and cancer-based pathways could be key for ZNF-related BRCA development. Interestingly, based on the results of ESTIMATE, ssGSEA, and GSEA analysis, we elucidated that our ZNF-gene signature had pivotal regulatory effects on the tumor immune microenvironment for BRCA.ConclusionOur findings shed light on the potential contribution of ZNFs to the pathogenesis of BRCA and may inform clinical practice to guide individualized treatment.

Dataset Information

Clinicopathologic and Prognostic Significance of the Zinc Finger of the Cerebellum Family in Invasive Breast Cancer.

Purpose

Methods

Results

Conclusion

Publications

Clinicopathologic and Prognostic Significance of the Zinc Finger of the Cerebellum Family in Invasive Breast Cancer.

Similar Datasets

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