Study On The Relationship Between Glucose And Lipid Metabolism And The Efficacy Of Immune Checkpoint Inhibitors In Non-small Cell Lung Cancer

Background and Purpose:Lung cancer is one of the leading causes of cancer-related deaths worldwide,and it ranks first in both incidence and mortality of malignant tumors in China.Non-small cell lung cancer(NSCLC)is the most common histological type of lung cancer.In recent years,immunotherapy,mainly immune checkpoints inhibitors(ICIs),has significantly improved the objective response rate(ORR)and overall survival(OS)of NSCLC patients.It shows significant efficiency,sustained clinical benefits and good tolerance.ICIs has become an indispensable part of the treatment of NSCLC patients.However,nearly half of patients still fail to benefit from it,thus showing some limitations.It is found that obesity and diabetes can affect the occurrence,development and prognosis of lung cancer,and fasting blood glucose,blood lipid,blood glucose fluctuation and abnormal metabolism can affect the immune function of the body and the therapeutic effect of lung cancer.In clinical work,it is observed that patients with abnormal glucose and lipid metabolism are accompanied by poor response and short survival time when using anti-tumor drugs such as ICIs.Therefore,it is very important to study the relationship between glucose and lipid metabolism and the efficacy of programmed death-1(PD-1)immune checkpoint inhibitors and the immune function of NSCLC,so as to find the potential beneficiaries,which can provide reference indicators for clinical decision-making,achieve the purpose of accurately screening patients and improving the prognosis of NSCLC.The purpose of this study is to analyze whether glucose and lipid metabolism is related to the efficacy of PD-1 inhibitor and immune function of NSCLC patients,so as to improve clinical decision-making and prognosis of patients.Methods:This study is a clinical retrospective study.Through the medical record room and electronic medical record system,89 patients who were treated with PD-1 inhibitor for 2 cycles or more in our hospital from January 1,2020 to December 31,2021 and were confirmed as NSCLC by pathology and imaging examination and met the inclusion and exclusion criteria were collected.We collected data on gender,age,tumor type,tumor stage,PD-L1 expression level,chronic comorbidities,height,weight,smoking history,and Fasting blood glucose(FBG),Total cholesterol(TC),Triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),lymphocyte subsets and other indicators before primary immunotherapy.Patients were followed up until May 31,2022.The primary endpoint was progression free survival(PFS),and the secondary endpoint was ORR at the second cycle.SPSS26.0 software was used for statistical analysis,and the truncated values of FBG,TC,TG,HDL-C and LDL-C were obtained by receiver operating characteristic curve(ROC)for group analysis.If the measurement data is normal distribution,it is expressed by the mean standard deviation,and the comparison between the two groups adopts t test.If the measurement data is non-normal distribution,it is expressed by the median and quartile,and the comparison between the two groups adopts Mann-Whitney U.The counting data is represented by an case(%),and the Chi-squared test is adopted.Kaplan-Meier method was used to draw the survival curve,and single factor analysis was conducted.Log-rank was used to test the survival.Multivariate Cox proportional hazard regression model was used for multivariate analysis.P<0.05 means that the difference is statistically significant,and the test level α=0.05.Because of the short follow-up time,most patients did not reach the death outcome and were not included in OS for analysis.Results:1.Univariate analysis showed that the prognosis of patients with NSCLC treated with PD-1inhibitor was related to their diabetes history,high FBG(FBG≥5.075mmol/L),low HDL-C(HDL-C≤1.615mmol/L),low LDL-C(LDL-C≤3.075mmol/L)before the first immunotherapy and age(≤60 years old).Correlation analysis between lymphocyte subsets and PFS showed no significant difference.2.Multivariate Cox proportional hazard regression analysis showed the correlation between prognosis of NSCLC patients treated with PD-1 inhibitor: FBG(HR: 1.86,95%CI: 1.145-3.023,P=0.012),HDL-C(HR: 3.469,95% CI: 1.519-7.925,P=0.003),age(HR: 0.576,95% CI: 0.364-0.910,P=0.018).3.The correlation analysis between the general characteristics of patients and blood glucose and blood lipid showed that the level of blood lipid was related to the clinical characteristics.There was significant difference in TC level between male and female patients(P=0.009).There were significant differences in TG levels among patients with different pathological types(P=0.013).The difference of HDL-C level in different tumor stages was statistically significant(P=0.026).4.The correlation analysis of blood sugar,blood lipid and lymphocyte subsets showed that: the higher FBG,the lower CD3+CD4+(P=0.018).In diabetic patients,the ratio of CD3-CD16+/56+ was higher(P=0.014).In patients with high TC,CD4+/CD8+ was lower(P=0.036).In patients with low TG,the absolute number of lymphocytes(P=0.024),total T lymphocytes(P=0.011),CD4+ lymphocytes(P=0.005)and CD8+ lymphocytes(P=0.05)are lower.Conclusion:Glucose metabolism and lipid metabolism are related to the efficacy of PD-1 inhibitor in NSCLC patients.History of diabetes,higher FBG,lower HDL-C,lower LDL-C and age(≤60 years old)are related to shorter PFS.FBG,HDL-C and age are independent predictors of the use of PD-1 inhibitor PFS in NSCLC patients.At the same time,the index of glucose and lipid metabolism is related to lymphocyte subsets in peripheral blood,suggesting that glucose and lipid metabolism may affect the efficacy of tumor immunotherapy by affecting the immune state of the body.