| Objective: Breast cancer is the most common cancer in women,threatening the health of women worldwide.With the establishment of molecular subtypes and the progress of comprehensive treatments including radiotherapy,chemotherapy,neoadjuvant therapy,and immune therapy,the mortality of breast cancer has been greatly reduced.However,there are still a number of patients undergo drug resistance,recurrence,metastasis,or lack of effective therapeutic targets,and the pathogenesis also remains unclear.The incidence of breast cancer has been rising over the past decades.It caused great misery to patients both physically and mentally,and also brought economic pressure.Thus,it is necessary to explore the underlying mechanism of breast cancer progression and search for factors that have diagnostic or prognostic value.Trough deeply investigating these potential targets,we may find theoretical basis for breast cancer individualized therapy.The aim of this research was to examine the expression of Heat Shock Protein A8(HSPA8)mRNA as well as HSPA8 protein in breast cancer cell lines and tissues collected from breast cancer patients.By analyzing clinical data,we explored the relationship between HSPA8 expression and clinicopathological behaviors and the prognostic value of HSPA8 in breast cancer patients.Furthermore,we conducted protein interaction and co-expression analysis of HSPA8 through online database.Taken together,HSPA8 may be a potential target in breast cancer treatment.Methods: 1.HSPA8 mRNA expression in breast carcinoma tissues,normal breast tissues,cancer cell lines as well as different subtypes of breast cancer were assessed with the TCGA,Oncomine,and CCLE databases,respectively.The correlation of HSPA8 expression and survival outcome was analyzed through online analysis tool Kaplan Meier Plotter.2.31 pairs of cancer tissue and para-cancer breast tissue were collected from patients who underwent modified radical mastectomy or breast conserving surgery from November 2019 to January 2020 at China Medical University Affiliated Shengjing Hospital,kept and transported in liquid nitrogen.Together with cell lines cultured in the laboratory,the HSPA8 mRNA and protein expressions were quantified by qRT-PCR and Western-blot.3.Tissues derived from 88 patients who underwent modified radical mastectomy or breast conserving surgery from 2006 to 2008 with at least ten years of follow-up were collected and made into tissue microarray for HSPA8 protein immunohistochemistry staining.According to the clinical and follow-up records,we analyzed the correlation of HSPA8 protein expression level with breast cancer prognosis,patients' clinicopathological characteristics,recurrence and metastasis.4.SPSS23.0 software was utilized to analyze the data.Chi-square test,Fisher's exact test,Student's t test,univariate and multivariate Cox regressions were used during the process.P<0.05 was considered statistically significant.Results: 1.The analysis of multiple databases showed that the expression of HSPA8 is consistently higher in breast cancer tissues than in normal breast tissues.2.Among all the subtypes,triple negative breast cancer showed the highest expression level of HSPA8.3.According to the Kaplan Meier Plotter database,HSPA8 expression is related to patients' prognosis.Those who expressed higher level of HSPA8 had significantly shorter overall survival and poorer prognosis,especially in triple negative breast cancer patients.4.By detecting collected clinical samples,we concluded that both HSPA8 mRNA level and protein level were significantly elevated in cancer tissues in comparison with cancer-adjacent breast tissues.Among all cell lines detected in the experiment,breast cancer cell lines MDA-MB-231,MCF-7,SK-BR-3 showed significantly higher HSPA8 expression than mammary epithelial cell line MCF-10 A.5.Immunohistochemistry analysis showed that patients with higher HSPA8 expression also had higher pTMN stage,more advanced histological grade,higher incidence of recurrence and metastasis,shorter DFS and OS.Conclusion: The expressions of HSPA8 mRNA and protein were up-regulated in breast cancer tissues compared to normal breast tissues,and its high expression correlated to shorter disease-free survival and over-all survival in cancer patients.It can serve as a prognostic factor as well as a potential target for breast cancer therapy.Moreover,HSPA8 expression was related to aggressive behaviors of breast cancer and functioned as a crucial oncogene.HSPA8 may serve as prognostic factor and potential target for breast cancer,especially triple negative breast cancer,and provide novel strategy for breast cancer diagnosis and treatment. |
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