| Objective:Detect the expression levels of ferroptosis-related regulatory factors GPX4,SLC7A11,ALOX15 and SQLE in breast cancer and paracancer tissues,and analyze the correlation between the four factors and clinicopathologic features of breast cancer patients and their prognostic value in breast cancer patients.Methods:Paraffin specimens of breast cancer tissues and paraneoplastic tissues from 112patients with surgically excised primary infiltrative breast cancer from January 2017 to January 2018 were collected retrospectively from the Department of Galactophore,First Hospital of Shanxi Medical University,and clinical information of the patients were gathered and documented.The expression levels of GPX4,SLC7A11,ALOX15 and SQLE in the paraffin specimens were measured by immunohistochemical SP method to investigate the variable manifestation of the four in breast cancer tissues and paraneoplastic tissues.The association between the expression status of the four and the clinico-pathological features of breast cancer patients was also evaluated,as well as the prognostic value for breast cancer patients.Quantitative data were indicated as mean±standard deviation and classified data were stated as absolute frequency using SPSS 23.0statistical software for statistical analysis;χ~2test or continuity-correctedχ~2test was used for inter-group comparisons,and the correlation between GPX4,SLCA711,ALOX15and SQLE was analyzed by Spearman rank correlation,and survival curves were plotted using Kaplan-Meier function;combined with the survival data of patients,single variable and multi-factor Cox regression models were used to analyze prognostic influences,and P<0.05 was considered statistically distinct.Results:1.GPX4 was highly expressed in 61 cases(54.5%)of breast cancer tissues and 18cases(16.1%)of paracancer tissues(P<0.01).SLC7A11 was highly expressed in 78(69.6%)breast cancer tissues and 37(33.0%)paracancer tissues(P<0.01).ALOX15was highly expressed in 88(78.6%)breast cancer tissues and 41(36.6%)paracancer tissues(P<0.01).SQLE was highly expressed in 87 breast cancer tissues(77.7%)and27 paracancer tissues(24.1%)(P<0.01).2.GPX4 expression level was significantly correlated with lymph node metastasis(χ~2=6.346,P=0.012),molecular typing(χ~2=10.960,P=0.012)and ER status(χ~2=11.399,P=0.001).The expression level of SLC7A11 was significantly correlated with lymph node metastasis(χ~2=15.326,P<0.001),molecular typing(χ~2=11.366,P=0.010),and ER status(χ~2=38.328,P<0.001).There was a statistically significant association between the expression level of ALOX15 and whether the lymph nodes metastasized in breast cancer patients(χ~2=6.332,P=0.012);the SQLE expression level was correlated with the size of tumor dimensions(χ~2=4.347,P=0.037),whether the lymph nodes metastasized(χ~2=8.348,P=0.004),TNM stage(χ~2=9.703,P=0.002),and HER-2 status(χ~2=43.155,P<0.001)had statistically significant associations.The expression levels of GPX4,SLC7A11,ALOX15 and SQLE were not significantly correlated with age,menstrual status and PR status of breast cancer patients(P>0.05).3.Kaplan-Meier survival analysis revealed that in breast cancer tissues,patients with high expression of GPX4,SLC7A11,and SQLE had a worse prognosis compared to those with low expression(P<0.05).there was no significant difference in prognosis between patients with high and low expression of ALOX15(P>0.05).4.Univariate Cox regression analysis showed that GPX4,SLCA711,SQLE expression,lymph node metastasis,ER status,HER2 status were statistically correlated with the prognosis of patients(P<0.05).Multifactorial Cox regression analysis indicated that there was still a statistical link between the status of SQLE expression and lymph node metastasis and the outcome of the patients(P<0.05).5.There were 45 cases of high expression and 28 cases of low expression of GPX4and SQLE;16 cases of high expression of GPX4 and low expression of SQLE;23 cases of low expression of GPX4 and high expression of SQLE,and there was a positive correlation between GPX4 and SQLE(P=0.002,r=0.292).Kaplan-Meier survival analysis showed that the survival rate of patients with high GPX4 and SQLE expression was lower than that of patients with high GPX4 expression and non-high SQLE expression(P=0.002).Conclusion:1.High expression of GPX4 and SLC7A11 in breast cancer tissues,was found to be linked to breast cancer lymph node metastasis,and ER status.High expression of GPX4 and SLC7A11 is detrimental to the survival of breast cancer patients,which suggests that both may participate in breast carcinogenesis and are prospective therapeutic targets.2.High expression of ALOX15 in breast cancer tissues was related to lymph node metastasis in breast cancer patients and may contribute to the metastasis of breast cancer.3.SQLE was highly expressed in breast cancer tissues,correlated with breast cancer tumor diameter,lymph node metastasis,TNM stage,HER-2 status,was unfavorable to breast cancer patients’prognosis,and could be an independent prognostic agent for breast cancer patients.It suggests that SQLE may be an oncogene.4.GPX4 was positively correlated with SQLE,and high expression of both suggested the poor prognosis,suggesting that the simultaneous targeting of GPX4 and SQLE inhibition in breast cancer patients would be more effective for the survival benefit of breast cancer patients. |
