CN-121975939-A - Application of ZNF473-AKT axis as target in diagnosis, treatment and prognosis evaluation of liver cancer

Abstract

The invention belongs to the technical field of biological medicine, and provides application of ZNF473-AKT axis as a target in diagnosis, treatment and prognosis evaluation of liver cancer in order to solve the limitations of the existing tumor diagnosis method in sensitivity and specificity. The diagnostic reagent is a reagent for detecting whether ZNF473 is highly expressed. The ZNF473 is highly expressed, and the AKT protein is activated at the phosphorylation level of Ser473 site to promote the proliferation and migration of tumor cells. Expression levels of phosphorylated AKT decreased after knockdown of ZNF473, whereas expression of phosphorylated AKT was restored upon addition of AKT agonist SC 79. These results suggest that ZNF473 may promote proliferation and migration of tumor cells by modulating AKT signaling pathways, providing experimental basis for revealing its mechanism of action in tumorigenesis and development.

Inventors

• REN YIFAN
• XU JUN
• WANG YAN
• ZHANG XIAOMIN
• LIU CHUANG
• WANG TONGXIANG

Assignees

• 山西医科大学

Dates

Publication Date

20260505

Application Date

20260210

Claims (5)

1. Application of ZNF473-AKT axis as target in preparing diagnostic reagent for liver cancer.
2. 2. The method according to claim 1, wherein the diagnostic reagent is a reagent for detecting whether ZNF473 is highly expressed.
3. 3. The use according to claim 2, wherein ZNF473 is highly expressed and AKT protein is activated at the phosphorylation level of Ser473 site to promote proliferation and migration of tumor cells.
4. The application of ZNF473-AKT axis as target in preparing medicine for treating liver cancer is characterized in that the medicine is medicine for inhibiting or antagonizing ZNF473 high expression, and medicine or reagent for inhibiting or reducing AKT protein phosphorylation level at Ser473 site.
5. The application of ZNF473-AKT axis as target in preparing reagent or medicine for prognosis evaluation of liver cancer is characterized in that ZNF473 high expression is an independent risk factor for poor prognosis of patient, and the risk ratio is total survival time HR=1.57, disease specific survival time HR=1.74 and progression-free survival time HR=1.47.

Description

Application of ZNF473-AKT axis as target in diagnosis, treatment and prognosis evaluation of liver cancer Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of a ZNF473-AKT axis serving as a target in diagnosis, treatment and prognosis evaluation of liver cancer. Background ZNF473 is a member of the zinc finger protein family, which has been found in recent years to exhibit high expression in a variety of tumor tissues. ZNF473 was significantly upregulated in a variety of cancer types by single cell sequencing and TCGA database analysis, suggesting that it may be a potential tumor marker. In addition, high expression of ZNF473 is closely related to malignant biological behaviors of tumors, including enhancement of cell proliferation, migration ability. Currently, diagnosis and prognosis of tumors rely mainly on histopathological examination and traditional molecular markers, but these methods have limitations in terms of sensitivity and specificity. Although some gene markers have been reported, their clinical application value still needs to be further verified. ZNF473, a novel potential marker, whose high expression is closely related to malignant characteristics and poor prognosis of liver cancer, has not yet been fully developed for its application in clinical diagnosis and treatment. Therefore, there is a need to develop ZNF 473-based tumor diagnosis and prognosis evaluation methods to make up for the deficiencies of the prior art. Disclosure of Invention The invention provides application of ZNF473-AKT axis as a target in diagnosis, treatment and prognosis evaluation of liver cancer in order to solve the limitations of the existing tumor diagnosis method in sensitivity and specificity. The invention is realized by the following technical scheme that the ZNF473-AKT axis is used as a target to be applied to preparing diagnostic reagents for liver cancer. Further the diagnostic reagent is a reagent for detecting whether ZNF473 is highly expressed. Furthermore, the ZNF473 is highly expressed, the AKT protein is activated at the phosphorylation level of the Ser473 site, and the proliferation and migration of tumor cells are promoted. The invention also provides application of the ZNF473-AKT shaft serving as a target in preparing a medicament for treating liver cancer, wherein the medicament is a medicament for inhibiting or antagonizing high expression of ZNF473, and a medicament or reagent for inhibiting or reducing phosphorylation level of AKT protein at Ser473 site. The ZNF473 high expression is an independent risk factor for poor prognosis of patients, and the risk ratio is total survival hr=1.57, disease-specific survival hr=1.74, progression-free survival hr=1.47. In a first aspect of the present invention, a novel tumor diagnosis marker based on ZNF473 gene expression is provided, which can effectively distinguish tumor tissue from normal tissue, and has a ROC area under the curve (AUC) reaching 0.947, and a high diagnosis efficacy. The second aspect of the present invention solves the shortcomings of the existing tumor prognosis evaluation method in predicting patient survival, and provides a reliable prognosis evaluation means through the significant correlation between high expression of ZNF473 and patient poor prognosis (total survival hr=1.57, disease-specific survival hr=1.74, progression-free survival hr=1.47). The third aspect of the invention solves the key problems in the research of proliferation and migration mechanisms of tumor cells, reveals a molecular mechanism of ZNF473 for promoting malignant biological behaviors of tumor cells by regulating and controlling an AKT signal path, and provides a theoretical basis for targeted therapy. In conclusion, the invention comprehensively verifies the clinical value of ZNF473 as a tumor diagnosis and prognosis evaluation marker by integrating single-cell sequencing, TCGA database analysis and multiple groups of cell experiments, clarifies the action mechanism of the ZNF473 and makes up the defects of the prior art. One of the technical schemes of the invention is to use a single-cell data analysis technology (TISCH database to download a.h5 format file, use R software MAESTRO and Seurat to process data, and use t-SNE method to perform cell clustering grouping) system to study the expression characteristics of ZNF473 in tumor tissues. The second technical scheme of the invention is to download RNAseq data (TPM format) and clinical data through TCGA database (TCGA-LIHC project), and analyze the expression difference of ZNF473 and the correlation with clinical pathological features by Wilcoxon rank sum test statistics. The third technical scheme of the invention is to verify the influence of ZNF473 on the proliferation and migration capability of tumor cells through cell functional experiments such as CCK8 experiments, colony formation experiments, scratch healing experiment