Clinical Significance Of Mutant P53,p63 And BRCA1 Protein Expression In Advanced Non-Small Cell Lung Cancer

Objective To investigate the factors affecting the expression of mutant p53,p63 and BRCA1 proteins in advanced NSCLC,and to clarify the relationship between the expression levels of mutant p53,p63 and BRCA1 proteins and the efficacy and prognosis.Methods Part I 226 patients with advanced NSCLC were admitted to our hospital from December 01,2017 to December 30,2020.According to the results of immunohistochemical semi-quantitative score,score<5 was defined as low expression,score ≥5 was defined as high expression,to explore the factors affecting the expression of mutant p53,p63 and BRCA1 proteins in advanced NSCLC.Part II 122 patients with advanced NSCLC were admitted to our hospital from September 1,2018 to October 30,2019.The tissues were grouped according to the expression of mutant p53,p63 and BRCA1 proteins.The choice of chemotherapy regimen was made according to clinical decision,and to observe the difference of therapeutic effect between high and low expression groups of mutant p53,p63 and BRCA1.The efficacy was evaluated according to the RECIST 1.1 Efficacy criteria for evaluating solid tumors,which were divided into four criteria: complete response,partial response,stable response and progressive response.The objective remission rate and progression-free survival in the high and low expression groups of mutant p53,p63 and BRCA1 were followed up to clarify the relationship between the expression levels of mutant p53,p63 and BRCA1 proteins and efficacy and prognosis.Results Part I(1)121 cases of lung squamous cell carcinoma:High expression of mutant p53 in 70 cases(57.8%),high expression of p63 protein in 104 cases(85.9%),high expression of BRCA1 in 42 cases(34.7%).105 cases of non-squamous non-small cell lung cancer:High expression of mutant p53 in 48 cases(45.7%),high expression of p63 protein in 17 cases(16.1%),and high expression of BRCA1 in 34 cases(32.4%).The expression of p63 was correlated with histopathology(P<0.05).(2)Univariate analysis:The expression rate of mutant p53 in advanced NSCLC of smoking group was higher than that of non-smoking group,and the expression rate of mutant p53 in low-differentiated advanced NSCLC tissues was higher than that of medium-differentiated and well-differentiated,the differences were statistically significant(P<0.05),and it was not related to gender,age,pleural effusion(P>0.05).The expression rate of p63 in advanced NSCLC of smoking group was higher than that of non-smoking group,the difference was statistically significant(P<0.05),and it was not related to gender,age,histological grade,pleural effusion(P>0.05).The expression rate of BRCA1 in low-differentiated advanced NSCLC was higher than that in medium-differentiated and well-differentiated tissues,and the difference was statistically significant(P<0.05),which was not related to gender,age,smoking history,pleural effusion(P>0.05).Logistic regression analysis showed that smoking history and histological grade were the two factors leading to the high expression of mutant p53 protein in advanced NSCLC tissues.The high expression of p63 protein in advanced NSCLC was associated with smoking history,and the high expression of BRCA1 in advanced NSCLC was associated with histological grade.(3)Spearman rank correlation analysis:The expression of mutant p53 was positively correlated with the expression of p63 in advanced NSCLC(P<0.05).The expression of mutant p53 was negatively correlated with the expression of BRCA1(P<0.05).The expression of p63 was unrelated to the expression of BRCA1(P>0.05).Part II(1)The ORR of the high expression group of mutant p53 was 22.0%,and the ORR of the low expression group was 56.7%.The efficacy of thehigh expression group of mutant p53 was worse than that of the low expression group,and the difference was statistically significant(P<0.05).ORR of the high of p63 expression group was 37.7%,and that of the low expression group of p63 was 41.4%.There was no difference in efficacy between the high expression group of p63 and the low expression group(P>0.05).The ORR of the high expression group of BRCA1 expression was 26.1%,and that of the low expression group of BRCA1 was 47.9%.The efficacy of the group of the high BRCA1 expression was worse than that of the low expression group,and the difference was statistically significant(P< 0.05).(2)The median PFS of the high expression group of mutant p53 was 20 weeks,and the low expression group was 28 weeks.The prognosis of the high expression group of mutant p53 was worse than that of the group with low expression,and the difference was statistically significant(P<0.05).The median PFS of the high expression group of p63 was 22 weeks,and the low expression group was 20 weeks.There was no significant difference in prognosis between the high expression group of p63 and the low expression group(P>0.05).The median PFS of the high expression group of BRCA1 was 18 weeks,and the low expression group was 28 weeks.The prognosis of the high expression group of BRCA1 was worse than that of the group with low expression,and the difference was statistically significant(P<0.05).The median PFS of the low-differentiated group was 20 weeks,and medium-differentiated group was 28 weeks,and well-differentiated group was 36 weeks.The prognosis of the low-differentiated group was worse than that of the group with medium-differentiated and medium-differentiated group,the difference was statistically significant(P<0.05).There was no significant difference in sex,age,pathological type,smoking history,pleural effusion and p63 protein expression(P>0.05).(3)Multivariate analysis:The risk of death in the low-differentiated group was 1.664-fold higher than the well-differentiated group(OR: 1.664,95%CI:1.175-2.357,P>0.05).The risk of death in the high expression group of mutant p53 was 2.486-fold higher than the low expression group(OR:2.486,95%CI:1.658-3.727,P<0.05).The risk of death in the high expression group of BRCA1 was 2.553-fold higher than the low expression group(OR:2.553,95%CI:1.698-3.837,P<0.05).Conclusion(1)The expression rates of mutant p53 and p63 in advanced NSCLC patients who smoked were higher than those of non-smoking patients,and the expression rates of mutant p53 and BRCA1 in low-differentiated advanced NSCLC were higher than those in medium and highly differentiated tissues.(2)The expression of mutant p53 in advanced NSCLC tissue was positively correlated with the expression of p63,and the expression of mutant p53 in advanced NSCLC tissue was negatively correlated with the expression of BRCA1.(3)The expression levels of mutant p53 and BRCA1 protein in advanced NSCLC tissues are prognostic factors of advanced NSCLC.