Developing ZNF Gene Signatures Predicting Radiosensitivity of Patients with Breast Cancer

Abstract

Adjuvant radiotherapy is one of the main treatment methods for breast cancer, but its clinical benefit depends largely on the characteristics of the patient. This study aimed to explore the relationship between the expression of zinc finger (ZNF) gene family proteins and the radiosensitivity of breast cancer patients. Clinical and gene expression data on a total of 976 breast cancer samples were obtained from The Cancer Genome Atlas (TCGA) database. ZNF gene expression was dichotomized into groups with a higher or lower level than the median level of expression. Univariate and multivariate Cox regression analyses were used to evaluate the relationship between ZNF gene expression levels and radiosensitivity. The Molecular Taxonomy Data of the International Federation of Breast Cancer (METABRIC) database was used for validation. The results revealed that 4 ZNF genes were possible radiosensitivity markers. High expression of ZNF644 and low expression levels of the other 3 genes (ZNF341, ZNF541, and ZNF653) were related to the radiosensitivity of breast cancer. Hierarchical cluster, Cox, and CoxBoost analysis based on these 4 ZNF genes indicated that patients with a favorable 4-gene signature had better overall survival on radiotherapy. Thus, this 4-gene signature may have value for selecting those patients most likely to benefit from radiotherapy. ZNF gene clusters could act as radiosensitivity signatures for breast cancer patients and may be involved in determining the radiosensitivity of cancer.

The role of zinc finger proteins in malignant tumors

“…35 Furthermore, high expression of ZNF644 as well as low expression of ZNF341, ZNF541, and ZNF653 are reported to influence sensitivity to radiation therapy in breast cancer. 36 Taken together, these data indicate that ZNFs are highly associated with ER, PR, and HER-2 expression in breast cancer and can affect cell proliferation, apoptosis, and drug resistance by regulating…”

Complex interaction and heterogeneity among cancer stem cells in head and neck squamous cell carcinoma revealed by single-cell sequencing

“…In our results, CSCs highly expressed tumor stemness marker genes, SOX2 and NANOG, ZNF and ZBTB families. It has been reported ZNF and ZBTB families were extensively involved in cancer development and cell differentiation ( 33 , 34 ). The substantial activation of ZNF and ZBTB families indicated their potential role in resulting in heterogeneity of tumors ( Figure 4B ).…”

Systematic profiling of alternative splicing of ZNF family in Colorectal cancer

“…ZNFs have been linked to the occurrence and progression of cancer, and alternative splicing of zinc nger proteins has been identi ed as an important factor in cancer development [32,33]. Different splicing patterns can produce various isoforms, which can generate proteins with different functions [34].…”