Preliminary Study On The Mechanism Of SLC7A11 In Ferroptosis And Prognosis Of Lung Cancer

Objective:The latest report shows that lung cancer is a malignant tumor of the second,mortality in the global morbidity,and hosted in the morbidity and mortality rate of chinese malignant tumors,and it is urgent to improve the low diagnosis rate and the recurrence of recurrence.Lung cancer ranks first in morbidity and mortality rate among malignant tumors.The early diagnostic rate needs to be improved urgently to prevent distant recurrence and metastasis.Ferroptosis is a newly find type of cell death.However,what kind of way to ferroptosis affects the occurrence and progress of lung cancer need more in-depth research.The research have shown that SLC7A11/GPX4 pathway is the key reductive pathway involved in inhibiting incidence of ferroptosis.However,the expression of related factors in different types of lung cancer and how does this effect need to be further explored.This research is aimed to discuss the expression difference of related molecules in SLC7A11/GPX4 pathway in different types of lung cancer and the influence of prognosis in patients with lung cancer,and to discuss the how does SLC7A11 effect to ferroptosis of lung cancer.Methods:Related differential gene expression of lung cancer ferroptosis was analyzed from TCGA and Oncomine,and the prognostic features of SLC7A11 and GPX4 gene in lung cancer were further verified by visiting http://kmplot.com/analysis/;the tissues in different types of lung cancer,and the expression of SLC7A11and GPX4 in A549 and H1975 cell lines of lung adenocarcinoma were tested by western blot;the study applied immunohistochemistry to detect the expression of SLC7A11 protein in 129 cases of lung cancer and tumor-adjacent tissue;combined with prognostic data of lung cancer patients,and prognostic follow-up data to perform statistical analysis,and further verified the expression of SLC7A11 in patients with lung cancer and the impact on long-term survival of patients;the ferroptosis model of lung cancer cell was established,and induced by ferroptosis drug erastin in accordance with different concentrations set;compared with the control group,related ferroptosis index of iron ion,GSH and MDA in the ferroptosis model were tested by establishing ferroptosis model of lung cancer cell.Results:The study showed that the expression of SLC7A11 m RNA in normal lung tissues was obviously lower than that in lung cancer tissues,and patients with lung cancer with high SLC7A11 expression was related to bad prognosis（P<0.05）from the database of TCGA and Oncomine;western blot was suggested that the expression of ferroptosis-related proteins SLC7A11 and GPX4 in tumor-adjacent tissue was significantly less than that in lung cancer tissues（P<0.05）;immunohistochemistry was suggested that the positive degree of SLC7A11 protein in para-carcinoma tissues was generally less than that in lung cancer tissues;the expression of SLC7A11 in poorly differentiated lung cancer tissues maybe relatively higher,indicating that the poor prognosis of lung cancer patients maybe associated with the high SLC7A11expression;ferroptosis inducer erastin may induce ferroptosis of lung cancer cell.With the increase of drug concentration,cell survival rate is lowered.The optimal ferroptosis Erastin-induced concentration of A549 and H1975 cell lines was selected for the following experiments;ferroptosis-related index of erastin-induced ferroptosis model in lung cancer cells:the index of MDA and Fe²⁺in experimental group were higher than control group,and GSH content was higher than experimental group（P<0.05）.Conclusions:（1）SLC7A11/GPX4 pathway related to ferroptosis was activated in lung cancer;（2）the high SLC7A11 expression of SLC7A11/GPX4 pathway indicated poor tissue differentiation,and poor patient prognosis;（3）ferroptosis-induced in lung cancer cells will become a new treatment option for lung cancer.