WITHDRAWN: HSPA8 is a New Biomarker of Triple Negative Breast Cancer Associated with Prognosis and Immune Infiltration

Abstract

Objective Triple negative breast cancer (TNBC) is a malignant tumor that endangers the health and lives of women all over the world in the 21st century. Heat shock protein member 8 (HSPA8/HSC70) is the chaperone gene of the heat shock protein family. It is involved in many cellular functions.For example, it promotes the circulation between ATP and ADP, participates in protein folding, and can change the vitality of the cell and inhibit its growth. HSPA8 overexpression in several human cancers reportedly leads to its malignant transformation. Nonetheless, the HSPA8 mRNA abnormal expression in TNBC and its diagnostic and prognostic significance remains to be elucidated. Methods TCGA, GEO, ONCOMINE,TIMER2.0, UALCAN, HPA, STRING and Kaplan-Meier plotter were conducted for bioinformatics analysis. HSPA8 protein expression was evaluated by Immunohistochemical method in TNBC tissues. Western blotting experiments were carried out to verify the results. Then the clinicopathological characteristics of patients with TNBC were analyzed by R software and Cox regression analysis. On this basis, a nomogram is constructed to estimate the 5-year overall survival. The prognostic Nomogram performance was calibrated and evaluated by calibration curve and receiver operating characteristic (ROC) curve . Results In this study, we discovered remarkably upregulated transcription of HSPA8 in breast cancer (BC) samples and TNBC samples relative to normal breast samples through bioinformatic analysis, which was further verified in clinical tissue samples and in experiments. Moreover, the transcriptional level of HSPA8 in BC samples and TNBC samples was positively associated with clinical parameters such as clinical tumor stage. Cox regression analysis revealed that the expression of HSPA8 in TNBC had significant clinical prognostic value. The nomogram and ROC analysis results demonstrated the strong predictive ability of HSPA8 in TNBC. KEGG and GO researches indicated that HSPA8 was mainly involved in partner-mediated autophagy, mRNA catabolism, neutrophil activation, immune response, protein targeting, RNA splicing, RNA catabolism and other biological processes.Immune infiltration analysis indicated that HSPA8 was significantly associated with immune cell subsets. Conclusions Our study findings demonstrate the potential diagnostic and prognostic significance of HSPA8 expression in TNBC, and elucidate the potential molecular mechanism of promoting the occurrence and development of TNBC. These results may provide new opportunities and research approaches for targeted therapies in TNBC.

HSPA8 Is a New Biomarker of Triple Negative Breast Cancer Related to Prognosis and Immune Infiltration

“…The research reveals the possible mechanism of HSPA8 in the occurrence and development of TNBC and the significance of clinical diagnosis, but there are still some limitations [ 73 ]. First, the evaluation of the role of HSPA8 is based on the database and some experiments, which has not been confirmed in vivo, so we need to further explore.…”