| BackgroundBreast cancer is the most common malignant tumor in women.According to the molecular typing agreed by St Gallen in 2011,breast cancer can be divided into four subtypes:Luminal A type,Luminal B type,human epithelial growth factor receptor 2(HER2)overexpressed and triple negative breast cancer(TNBC),TNBC is characterized by high aggressiveness,high recurrence rate and high metastasis rate,with poor prognosis.TNBC refers to breast cancer with negative expression of estrogen receptor(ER),progesterone receptor(PR)and HER2,which accounts for 15-20% of all breast cancers.Up to now,the clinical treatment effect is poor,which is the difficulty and focus of breast cancer treatment.Therefore,it is particularly important to look for targeted therapeutic targets for triple-negative breast cancer.Our preliminary results show that EGFR and EZH2 are highly expressed in triple negative breast cancer and are related to lymph node metastasis and tumor stage.The two may act together on the PI3K/AKT/FOXO signaling pathway of Phosphoinositide 3-kinase,thus playing an important role in the occurrence,development,invasion and metastasis of breast cancer.The PI3K/AKT/FOXO signaling pathway is involved in regulating the survival,proliferation,differentiation and metabolism of tumor cells.Currently,there are few reports on the PI3K/AKT/FOXO1 signaling pathway in breast cancer.Therefore,the purpose of this study was to investigate the expression and clinical significance of PI3Kp85,Akt and FOXO1 in triple negative breast cancer.ObjectiveTo investigate the effect and clinical significance of PI3Kp85,Akt and FOXO1 in TNBC by detecting the expression of PI3Kp85,Akt and FOXO1 in triple negative breast cancer tissue,benign breast tumor tissue and adjacent normal breast tissue.At the same time,bioinformatics software was used to find the PI3Kp85,AKT and FOXO1 co-enrichment pathway map in the PI3K/AKT/FOXO1 signaling pathway,so as to preliminarily explore its mechanism of action,so as to provide a new therapeutic target for the accurate treatment of TNBC.Methods30 cases of triple negative breast cancer tissue and para-carcinoma normal breast tissue were collected from the gastrointestinal gland surgery department of the first affiliated hospital of guangxi medical university from April 2018 to December 2019,and 30 cases of breast tissue specimens with benign pathological results and minimally invasive spiral biopsy of mammary mass by malmotonone were collected.They were divided into the triple negative breast cancer group(TNBC group),the benign breast tumor group(L group)and the para-cancer normal breast group(N group),with 30 cases in each group.The expressions of PI3Kp85,Akt and FOXO1 in 90 tissue samples were detected by Western blot,rt-qpcr and immunohistochemistry.Tumor size,lymph node metastasis,histological grading,Ki67,P53 and other clinicopathological indicators of breast cancer patients were collected.Bioinformatics software GO and KEGG were used to find the PI3Kp85,AKT and FOXO1 co-enrichment pathway in the PI3K/AKT/FOXO1 signaling pathway.Results1.Western blot detection of the expression levels of PI3Kp85,Akt and FOXO1: compared with the L group and the N group,the expression levels of PI3Kp85 and Akt were increased in the TNBC group(P < 0.05)and decreased in the FOXO1 group(P < 0.05).There was no significant difference in the expression levels of PI3Kp85,Akt and FOXO1 between group L and group N(P >,0.05).2.Real-time quantitative fluorescence PCR was used to detect the expression of PI3Kp85,Akt and FOXO1 mRNA.Compared with the L group and the N group,the mRNA levels of PI3Kp85 and Akt in TNBC group were increased(P< 0.05),and the mRNA levels of FOXO1 were decreased(P < 0.05).There was no significant difference in the expression levels of PI3Kp85,Akt and FOXO1 between group L and group N(P >,0.05).3.Immunohistochemical(SP)results showed that the expression levels of PI3Kp85 protein and Akt protein in TNBC group were increased(P < 0.05)and FOXO1 protein was decreased(P < 0.01)compared with L group and N group.There was no significant difference in the expression levels of PI3Kp85,Akt and FOXO1 between group L and group N(P >,0.05).4.The expression levels of PI3Kp85,Akt and FOXO1 proteins and mRNA were correlated with lymph node metastasis and clinical stage(P<0.05),independent of patients’ age,menopausal status,tumor size,histological grading,ki-67 and P53 proteins(P>0.05),in the triple negative breast cancer tissues with lymph node metastasis and higher clinical stage,the expression levels of PI3Kp85 and Akt were higher,while the expression levels of FOXO1 were lower.5.Correlation analysis between Akt and the expression levels of PI3Kp85 and FOXO1 in breast cancer tissues.Pearson correlation analysis showed that there was a positive correlation between Akt and PI3Kp85 in breast cancer tissues,r=0.647,P=0.000,showing a strong correlation.There was no correlation between Akt and FOXO1,r=-0.162,P=0.392.There was no correlation between PI3Kp85 and FOXO1,r=-0.045,p=0.8156.Bioinformatics analysis showed that PI3Kp85,Akt and FOXO1 were enriched together in the pathway.PI3 K pathway is an important pathway in the overexpression of HER2 and TNBC breast cancer.PI3 K phosphorylates Akt,and Akt activates the downstream signaling pathway FOXO1,thereby regulating gene expression.Conclusions1.The high expression of PI3Kp85 and Akt may cooperatively participate in the occurrence and development of triple-negative breast cancer and promote the metastasis of triple-negative breast cancer.2.The low expression of FOXO1 may be involved in the occurrence and development of triple-negative breast cancer and promote the metastasis of triple-negative breast cancer.3.The poor prognosis of triple-negative breast cancer may be related to the high expression of PI3Kp85 and Akt and the low expression of FOXO1.4.The PI3K/AKT/FOXO1 signaling pathway plays an important role in the occurrence,development and biological behavior of triple-negative breast cancer,and may become a reference index for predicting the prognosis of triple-negative breast cancer. |
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