Expression And Clinical Significance Of Mutant P53 And HIF-1α In Advanced Non-small Cell Lung Cancer

ObjectiveTo study the expression and clinical significance of mutant p53 and HIF-1αin advanced non-small cell lung cancer tissues.MethodsPart IThe cancer tissue specimens and clinicopathological data of 200patients with advanced non-small cell lung cancer who were pathologically diagnosed in our hospital from January 1,2018 to January 31,2020 were collected.Immunohistochemistry was used to detect the expression of mutant p53 and HIF-1αin advanced non-small cell lung cancer tissues,and to explore the related factors affecting the expression of mutant p53 and HIF-1α.Part ⅡA total of 120 eligible patients with advanced non-small cell lung cancer from September 1,2019 to October 31,2020 in our hospital were enrolled.All patients were followed up to January 31,2022,and the relationship between the expression of mutant p53 and HIF-1αand chemotherapy efficacy and survival prognosis was analyzed.ResultsPart I(1)Among the 200 patients with advanced non-small cell lung cancer,the positive expressions of mutant p53 and HIF-1αwere 107 cases(53.5%)and 147 cases(73.5%),respectively.Among the 108 cases of lung squamous cell carcinoma,the positive expression of mutant p53 and HIF-1αwas 62 cases(57.4%)and 80 cases(74.1%)respectively;Among the92 cases of lung adenocarcinoma,45 cases(48.9%)and 67 cases(72.8%)had positive expression of mutant p53 and HIF-1α,respectively.There was no significant difference in the positive expression rates of mutant p53 and HIF-1αbetween lung squamous cell carcinoma and lung adenocarcinoma(x~2 were 1.44 and 0.04 respectively,P>0.05).(2)Univariate analysis:(1)The positive expression rate of mutant p53in patients with smoking history was higher than that in patients without smoking history,and the positive expression rate in poorly differentiated tissues was higher than that in moderately and well differentiated tissues(P<0.05).The expression of mutant p53 was not related to gender,age,drinking history,maximum tumor diameter and tumor location(P>0.05).The expression of HIF-1αwas related to the degree of tumor differentiation(the positive expression rates of HIF-1αin poorly differentiated,moderately differentiated and highly differentiated tissues were 60.0%,68.2%and 82.2%respectively,x~2=7.064,P=0.029),while the expression of HIF-1αwas not related to sex,age,smoking history,drinking history,tumor maximum diameter and tumor location(P>0.05).(3)Spearman correlation analysis:The expressed.levels of mutant p53and HIF-1αin advanced NSCLC tissues were positively correlated(rs=0.167,P=0.018).Part Ⅱ(1)The objective response rate of positive mutant p53 expression group(24.6%)was lower than that of negative p53 expression group(41.8%)(P<0.05).The objective response rate of Hif-1αpositive expression group(27.5%)was lower than that of negative expression group(48.3%)(P<0.05).(2)The median overall survival time(m OS)of mutant p53 negative expression group was higher than that of positive expression group,and the median m OS was 11.4 months and 7.7 months respectively,and the difference was statistically significant(P<0.002).The median overall survival time(m OS)of HIF-1αnegative expression group and positive expression group was 12.2 months and 8.9 months,respectively,and the difference was statistically significant(P<0.05).(3)Prognostic analysis:(1)Univariate analysis:Mutant p53,HIF-1α,pathological type and maximum tumor diameter were related to the prognosis of the patients,but gender,age,smoking history,drinking history and tumor location were not related to the prognosis(P>0.05).(2)Multivariate analysis:Mutant p53 and HIF-1αwere associated with the prognosis of patients(P<0.05),and were independent risk factors for the prognosis of advanced non-small cell lung cancer.Conclusion(1)The positive expression rate of mutant p53 in advanced NSCLC tissues in smoking group was higher than that of non-smoking group,and the positive expression rate of mutant p53 and HIF-1αin advanced NSCLC tissue of poorly differentiated group was higher than that of moderately and well differentiated group.(2)The expression levels of mutant p53 and HIF-1αin advanced NSCLC tissues were positively correlated.(3)The expression levels of mutant p53 and HIF-1αcan be used as poor predictors of chemotherapy effect and prognosis in advanced non-small cell lung cancer.