The Prognostic Impact Of TTF-1 Expression In Patients With Advanced Lung Adenocarcinomas In A Chinese Population

Objectives Lung cancer is one of the highest morbidity and mortality tumors in China and the world.It is a malignant disease that seriously endangers people’s lives and health in today’s society.Thyroid transcription factor 1(TTF-1)is a routine index to evaluate the diagnosis of lung cancer.it is common in lung adenocarcinoma and may regulate the biological behavior of lung cancer.Lung adenocarcinoma,as a pathological subtype of lung cancer,has been shown to be more responsive to pemetrexed,especially those with RET and ROS1 rearrangements.Since TTF-1 is a conventional marker for lung adenocarcinoma,which is usually more sensitive to pemetrexed chemotherapy than squamous cell carcinoma,we speculate that TTF-1 may further predict subgroups of pemetrexed-sensitive lung adenocarcinomas.In order to elucidate the role of TTF-1expression as a predictor and / or prognostic indicator in advanced lung adenocarcinoma and to evaluate whether patients with positive TTF-1 expression are more sensitive to pemetrexed chemotherapy,we studied the relationship between TTF-1 expression,molecular characteristics,chemotherapy response and overall survival in patients with advanced lung adenocarcinoma.Methods We analyzed the clinical,pathological,molecular characteristics,treatment regimen and overall survival of 209 patients with lung adenocarcinoma who had been detected by TTF-1 and treated continuously in our hospital.We used chi-square test and t-test to evaluate the relationship between TTF-1 expression and clinical and pathological features.The univariate effects of clinicopathology and TTF-1 expression on overall survival were evaluated by Kaplan-Meier and compared by log-rank test.Cox proportional hazard regression was used for multivariate modeling to assess the impact of TTF-1 expression on overall survival and to adjust potential confounding factors.In addition,we have established a nomogram model to estimate the prognostic value of our marker TTF-1.Results TTF-1 expression was positive in 166(79%)and negative in 43(21%)patients who were reviewed.Moreover,there was no significant differencebetween the clinicopathologic features of TTF-1 positive and TTF-1 negative tumors.In univariate analysis,the overall survival time of patients with positive TTF-1 expression was significantly longer than that of patients with negative TTF-1 expression(22.7 months VS11.8 months,P < 0.0001).In multivariable analysis,overall survival of patients with TTF-1 positive tumors were dramatically longer than that of patients with TTF-1 negative tumors((HR 0.42,95%CI 0.29-0.61,P<0.0001)),overstepping the prognostic impact of Karnofsky performance status and receipt of first-line combination chemotherapy or targeted therapy.In patients with advanced lung cancer with positive and negative TTF-1,the duration of initial treatment in the pemetrexed chemotherapy group was longer than that in the non-pemetrexed chemotherapy group.Conclusion TTF-1 expression was associated with an improved survival in patients with advanced lung adenocarcinomas.Both patients,either TTF-1 positive or negative,could benefit from the first-line chemotherapy or pemetrexed treatment option.However,as discovered by our investigation,TTF-1 cannot forecast a portion of the lung adenocarcinomas that had a selective sensitivity to pemetrexed.