Identification and validation of a novel zinc finger protein-related gene-based prognostic model for breast cancer

Abstract

Background Breast 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. Methods We 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. Results In 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. Conclusion Our findings shed light on the potential contribution of ZNFs to the pathogenesis of BRCA and may inform clinical practice to guide individualized treatment.

The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer

“…We also listed the other signatures that focus more on short-term survival, such as 1-year, 2-year, 3-year, and 5-year survival. We found our signature have similar short-term survival (3-year) prognostic value compared with them, such as the ferroptosis-related gene signature ( Wang et al, 2021a ; Wu et al, 2021a ; Zhu et al, 2021b ), pyroptosis-related gene signature ( Chen et al, 2022 ), necroptosis-related gene signature ( Yu et al, 2022 ), apoptosis-related gene signature ( Zou et al, 2022 ), zinc finger protein-related gene signature ( Ye et al, 2021 ), autophagy-related gene signature ( Lin et al, 2020 ), and metabolic-related gene signatures ( Lu et al, 2022b ). In addition, our model only involves four genes, while other models (11/13) tend to have more, which is more convenient to use to a certain extent.…”

“…To further explore the predictive ability of our signature, a comparison was performed among several significant molecular signatures employed for predicting OS in patients with BC. Compared with the other signature, such as ferroptosis, necroptosis, pyroptosis, and immune-related ( Lin et al, 2020 ; Zhong et al, 2020 ; Wang et al, 2021a ; Wu et al, 2021a ; Zhu et al, 2021b ; Ding et al, 2021 ; Ye et al, 2021 ; Lu et al, 2022a ; Lu et al, 2022b ; Chen et al, 2022 ; Chu et al, 2022 ; Yu et al, 2022 ; Zou et al, 2022 ), our signature indicated much higher AUCs, which indicated a better predictive ability, especially in predicting the long-term survival status. Furthermore, we constructed a prognostic nomogram that could simplify treatment decision-making for patients with BC.…”

Transcriptomic Profile of Canine Mammary Ductal Carcinoma

“…Thus, high expression of MECOM is related to an increased risk of early death. Moreover, the higher the expression, the more advanced the stage of the disease [ 38 ].…”

ZNF480 influences the prognosis, pathogenesis, and immune microenvironment in patients with lower-grade glioma

“…In recent years, there has been increasing evidence that KRAB-ZNFs promote tumor cell proliferation, invasion, and migration and help tumors evade the killing effects of host immune surveillance [ 7 , 8 ]. For example, multiple ZNF genes play key roles in the regulation of the tumor immune microenvironment (TME) in breast carcinoma, shortening the overall survival (OS) of patients [ 9 ]. Moreover, overexpression of ZNF655 promotes the proliferation and migration of glioma cells and inhibits apoptosis of cells by activating AURKA [ 10 ].…”