Correlation Between Telomere Length And Therapeutic Effect Of TKI In Patients With NSCLC And Risk Of Papillary Thyroid Carcinoma

Part1:Correlation between telomere length and therapeutic effect of TKI in patients with NSCLCLung cancer is the malignant tumor with the highest morbidity and mortality,and it shows a trend of continuous increase and rejuvenation in China.Gefitinib is currently one of the mostly used epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)recommended for treating non small cell lung cancer.However,factors that predict treatment prognosis to EGFR-TKIs remain elusive.Telomere is a human chromosome end-protection complex composed of the short repeat nucleotide sequence MTTAGGGM.The current study found that telomeres are closely related to the occurrence,development,prognosis and drug resistance of various tumors.The objective of this study is to investigate whether leukocyte relative telomere length(RTL)can be used as a prognostic biomarker of EGFR-TKIs therapy.In this study,182 patients with stage IIIB or IV lung adenocarcinoma were recruited and treated with gefitinib as first-line monotherapy.Leukocyte RTL of each patient was measured using quantitative polymerase chain reaction protocol and calculated according to Cawthon’s formula.Finally,we examined the association between leukocyte RTL and prognosis or drug resistance of advanced lung adenocarcinoma to gefitinib treatment.Our results indicated that compared with long RTL,short leukocyte RTL was significantly associated with poor prognosis in all patients after gefitinib treatment(OS:14.3 months vs 19.1 months,p=0.017;progression-free survival:10.3 months vs.13.0 months,p=0.164).In addition,statistical analysis showed that relative telomere length was associated with short OS in EGFR-driven gene-positive patients,adjusted for age,gender,and smoking history:hazard ratio(HR)=1.65,95%confidence interval(CI)=1.28-2.12;p value=0.006.Our results highlight the clinical potential of leukocyte RTL as a novel biomarker in advanced lung adenocarcinoma treated with EGFR-TKIs.Part2:Leukocyte telomere length and risk of papillary thyroid carcinomaThyroid cancer is the most common endocrine system malignant tumor,and its incidence is increasing year by year.It is more common in young women and is divided into papillary,follicular,myeloid and undifferentiated carcinoma.The telomere is mainly composed of the short repeat nucleotide sequence "TTAGGG",which is a DNA-protein complex at the end of human linear chromosomes.As the cell divides,the telomere length gradually shortens,which leads to the cell not adapting well to environmental changes,resulting in cell division being blocked and tissue replenishment being disturbed.Telomere length may contribute to predisposition of papillary thyroid cancer(PTC).To test this hypothesis,we examined the association between leukocyte telomere length and PTC risk.Case-control study in a Chinese Han population.A total of 1,200 PTC cases and 1,201 age-and sex-matched healthy controls were included in the study.Odds ratios(ORs)and 95%confidence intervals(CIs)were calculated by logistic regression.Short relative telomere length(RTL)was significantly associated with elevated risk of PTC(OR=1.61,95%CI=1.35-1.92,p=1.30×10-7).Interestingly,when individuals were categorized into four groups based on quartiles distribution of RTL in controls,we observed a reverse U-shape association between telomere length and PTC risk.As compared with those in the first quartile(the longest)as the reference group,ORs(95%CIs)are 5.61(4.04-7.78)(p=6.10×l0-25),9.33(6.78-12.83)(p=6.99×10-43)and 1.23(0.83-1.81)(p=0.300)for individuals in the second,third and fourth(the shortest)quartile.This reverse U-shaped relationship was more apparent in younger individuals.Our findings suggest that RTL is significantly associated with susceptibility of PTC.There is an obvious reverse U-shape association between telomere length and PTC risk.Telomere length might be a potential,pronouncing biomarker to identify individuals with high-risk to develop PTC.