Effect Of TIM-3 And CONUT Score On Locally Advanced And Advanced Stage Driver Gene Negative NSCLC Patients Treated With Radiotherapy

Objective: To evaluate the clinical value of T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)and controlling nutritional status(CONUT)score in predicting the efficacy and prognosis of locally advanced and advanced stage driver gene negative non-small cell lung cancer(NSCLC)patients treated with radiotherapy.Methods: The clinical data of 77 patients with stage IIIB～IV driver gene negative NSCLC who underwent chest radiotherapy between January 2017 and December 2019 were retrospectively analyzed.Expression of TIM-3 was detected by immunohistochemistry.CONUT score was calculated using total lymphocyte count,serum albumin and cholesterol levels from blood samples collected 1 week before radiotherapy and group them according to the cut off2.The value of TIM-3,CONUT score on therapeutic effect and prognosis was evaluated.SPSS21.0 software was used for statistical analysis.Results:1.TIM-3 expression,CONUT score and clinicopathological features of patients before radiotherapyTIM-3 was expressed in cell membrane and cytoplasm in tumor tissues.The positive expression rate of TIM-3 was 45.5%(35/77).Significant associations were detected between TIM-3 expression and the age of patients(P<0.05),and CONUT score(P<0.05).The cutoff value 2 was determined for the CONUT score,and the patients were divided into high(n=43)and low(n=34)CONUT groups.CONUT score was related to TIM-3 expression(P<0.05).Spearman correlation analysis showed CONUT score was related to the expression of TIM-3(P<0.05).2.Associations between TIM-3 and CONUT score and the radiotherapeutic effectThe objective response rate(ORR)of 77 patients was 40.3%(31/77).Patients with TIM-3 positive expression and high CONUT score had significantly lower ORR of radiotherapy(P<0.05).Logistic regression analysis showed that the expression of TIM-3 was a risk factor for radiotherapeutic effect.3.Prognostic value of TIM-3 expression and CONUT score with patients treated with radiotherapyThe median progression-free survival(PFS)and median overall survival(OS)of all patients were 4.2 months and 10.4 months,respectively.In the patient group with TIM-3 positive expression,both median PFS(3.1 vs.4.6months,P<0.05)and OS(8.5 vs.12.8 months,P<0.05)were shorter than the group with TIM-3 negative expression.Both median PFS and OS were significantly shorter in high CONUT score group than low CONUT score group(3.4 vs.5.4 months,P<0.05;8.4 vs.12.7 months,P<0.05,respectively).Univariate analysis showed that TNM stage,TIM-3 expression,CONUT score,therapeutic method,and radiotherapeutic effect were found to be significant for both PFS and OS.By COX multivariate regression analysis,TIM-3 expression,CONUT score,and radiotherapeutic effect were the independent prognostic factors for PFS,while only radiotherapeutic effect was the independent prognostic factor for OS.Conclusions:1.The expression of TIM-3 and CONUT score were negatively correlated with the efficacy of radiotherapy,and the expression of TIM-3might be a risk factor for the effect of radiotherapy.2.The expression of TIM-3 and CONUT score were negatively correlated with the prognosis of radiotherapy,and TIM-3 and CONUT score were found to be the independent prognostic factors for PFS.