Correlation Analysis Between TTF-1 Expression And Chemosensitivity And Prognosis Of Advanced Small Cell Lung Cancer Patients Treated With First-line Platinum-based Chemotherapy

Background and purposeLung cancer is a malignant tumor originating from bronchial mucosa or gland.Its morbidity is the first in the country and often causes poor prognosis due to insufficient early diagnosis.Lung cancer is a serious disease affecting human health.It can be divided into two major categories,non small cell lung cancer and small cell lung cancer which accounts for about 15%.Non-small cell lung cancer can be further divided into adenocarcinoma,squamous cell carcinoma,large cell carcinoma,neuroendocrine tumor and sarcomatoid carcinoma.Thyroid transcription factor 1(TTF-1)is a nuclear transcriptional protein that regulates the expression of a variety of lung specific genes.In lung structure,TTF-1 is expressed in II alveolar epithelial cells and Clara cells,and plays an important role in the regulation of the expression of A,B,C and Clara cell secretory proteins.According to the different histologic subtype of lung cancer,the expression of TTF-1 is different.TTF-1 is more often expressed in lung adenocarcinoma and small cell lung cancer,and is less expressed in squamous and large cell lung cancer.The positive expression of TTF-1 in small cell lung cancer can reach 85-90%.The study shows that in non-small cell lung cancer(NSCLC),especially in lung adenocarcinoma,TTF-1 positive expression has a better prognosis.The negative expression of TTF-1 is associated with the histologic subtype of invasive mucinous adenocarcinoma and the low mutation rate of EGFR,which indicates that the prognosis of lung adenocarcinoma is poor.However,for small cell lung cancer,the prognostic value of TTF-1 expression is still controversial,and there is less research about the correlation between TTF-1 expression and SCLC chemotherapy efficacy.The purpose of this study was to investigate the relationship between TTF-1 positive expression and the therapeutic effect of platinum chemotherapy in the front line of locally advanced or metastatic small cell lung cancer and its prognostic value.MethodsThe clinical data of 144 patients with locally advanced or metastatic SCLC who were diagnosed and treated with platinum regimen from June 1,2012 to December 31,2015 in the First Affiliated Hospital of Zhengzhou University were collected.TTF-1 expression in tumor tissues of 144 was detected by immunohistochemistry.Two experienced pathologists in the hospital are responsible for reviewing immunohistochemical sections.All patients enrolled in the study reviewed chest and upper abdomen CTs every two weeks.According to response evaluation criteria in solid tumors(RECIST)1.0 to evaluate the curative effect and calculating the disease control rate(DCR),objective response rate(ORR),progression free survival(PFS)and overall survival(OS)of patients.Follow up by case information enquiry or telephone.Chi-square test and logistic regression model were used to analyze the relationship between the expression of TTF-1 and the response rate of chemotherapy.Kaplan-Meier and Cox proportional hazards regression model were used to analyze the effect of TTF-1 expression on survival.Results1.Among the 144 patients,120(83.3%)had positive expression of TTF-1,24(16.7%)had negative expression of TTF-1.The positive expression of TTF-1 was not related to age,sex,smoking history,clinical stage and Ki-67 positive expression rate.2.The ORR of first-line chemotherapy in TTF-1 positive patients(85.8%)was higher than that in negative patients(66.7%),the difference was statistically significant(P=0.024).Analyzing the DCR,we observed there was no significant difference between TTF-1 positive patients(98.3%)and TTF1 negative patients(95.8%),p = 1.000.Logistic regression analysis showed that TTF-1 expression was an independent predictor of response rate(OR=3.029,P=0.028).3.The differences of PFS(9.0 months vs 7.0 months,P=0.119)and OS(14.0 months vs 11.5 months,P=0.115)between TTF-1 positive expression and negative expression patients were not statistically significant.Conclusion1.The expression of TTF-1 is associated with response rate in locally advanced or metastatic SCLC patients treated with first-line platinum based chemotherapy.TTF-1 expression may be a biomarker to predict chemosensitivity.2.The PFS and OS in patients with TTF-1 positive expression or negative expression were no significant difference.TTF-1 had no prognostic value concerning OS and PFS.