Expression And Clinical Significance Of LASP1 Gene In HR+/HER-2+ Breast Cancer

Purpose: To detect the expression of LASP1 in HR+/HER-2+breast cancer,and analyze the relationship between LASP1 expression and HR+/HER-2+breast cancer clinicopathological parameters and patient prognosis.Methods: GEPIA database,TCGA database and R language were used to analyze the expression of LASP1 in breast cancer and its relationship with the prognosis of breast cancer,and the expression of LASP1 in HR+/HER-2+breast cancer and its relationship with HER-2,ER and PR.200 postoperative specimens of breast cancer patients from Yantai Yuhuangding Hospital affiliated to Qingdao University were collected,and their pathological specimens were subjected to immunohistochemical experiments to analyze the relationship between the expression of LASP1 in HR+/HER-2+breast cancer and clinicopathological parameters and patient prognosis.Real time quantitative PCR and Western blot were used to detect the expression of LASP1 in MCF-10 A,MDA-MB-231,MCF-7,BT-474,and SKBR3 cell lines.CCK-8 cell proliferation test and scratch test were used to verify the effect of LASP1 expression on breast cancer cell proliferation and migration.Result:1.Bioinformatics analysis showed that LASP1 was highly expressed in breast cancer and negatively correlated with prognosis;LASP1 is highly expressed in HR+/HER-2+breast cancer.In mechanism,LASP1 is related to HER-2 and ER,but not PR.2.The immunohistochemical results showed that the high expression rate of LASP1 in HR+/HER-2+breast cancer was 74%,which was much higher than that in HR-/HER-2+,HR+/HER-2-,and HR-/HER-2-groups,with the high expression rates of24%,18%,and 20%,respectively(P<0.001).3.In HR+/HER-2+breast cancer,the expression of LASP1 was correlated with lymph node metastasis(P=0.002),TNM stage(P=0.015),and histological grade(P=0.012).4.Univariate analysis showed that TNM stage(p<0.01),histological grade(p=0.004)and LASP1 expression status(P<0.01)were negatively correlated with the DFS of HR+/HER-2+breast cancer.Three factors with significant differences in univariate analysis were included in the COX risk regression model for multivariate analysis.The results showed that TNM stage(P=0.006),LASP1 expression status(P=0.039)was an independent prognostic factor for DFS in HR+/HER-2+breast cancer patients.5.Kaplan-Meier survival curve showed that the median DFS of the LASP1 high expression group was 70.047 months,while the median DFS of the low expression group was 79.242 months(P<0.05).The five-year disease-related survival rate in the LASP1 high expression group was 87.5%,lower than 94.7% in the low expression group.6.The results of Real time quantitative PCR and Western blot showed that LASP1 was highly expressed in BT-474 cell line.7.The BT-474 LASP1 knockdown group and the MDA-MB-231 LASP1 overexpression group were constructed with plasmid,and the CCK-8 cell proliferation experiment and scratch experiment were carried out.The results showed that the LASP1 knockdown group inhibited the proliferation and migration of breast cancer cells,and the LASP1 overexpression group promoted the proliferation and migration of breast cancer cells.Conclusion: The high expression of LASP1 in HR+/HER-2+breast cancer is associated with clinicopathological factors such as lymph node metastasis,TNM staging,histological grading,and the high expression of LASP1 is associated with the poor prognosis of HR+/HER-2+breast cancer patients.It is suggested that LASP1 can be used as a prognostic factor for HR+/HER-2+breast cancer.The high expression of LASP1 in BT-474 cell line can promote the proliferation and migration of breast cancer cells.