从遗传关联到临床表型:中性粒细胞胞外诱捕网在头颈部鳞状细胞癌发生发展中的临床意义OA

Objective To investigate the causal relationship between neutrophil extracellular traps(NETs)and head and neck squamous cell carcinoma(HNSCC)using Mendelian randomization(MR)methods,and to explore the clinical significance of NETs in the occurrence and development of HNSCC.Methods Data related to NET biomarker myeloperoxidase-DNA complex(MPO-DNA)complex and HNSCC were obtained from the pooled statistical data of the Genome-Wide Association Study database(GWAS).This study was reviewed and approved by the Medical Ethics Com-mittee,and informed consent was obtained from patients.Patients with HNSCC admitted to Department of Oral Maxillo-facial,the First Affiliated Hospital of Harbin Medical University were included as the research group,and volunteers matched for age and gender were randomly selected from the Clinical Examination Center as the control group.The lev-els of MPO-DNA and citrullinated histone H3(CitH3),two markers of NETs,as well as the levels of soluble adhesion factor CD44 variant 6(CD44v6)and leukocyte differentiation antigen CD 109,markers of lymph node metastasis,were measured in all subjects.Blood coagulation indicators,including plasma prothrombin time(PT),activated partial throm-boplastin time(APTT),thrombin time(TT),D-dimer(DD),and fibrinogen levels(FIB),were recorded to analyze the rela-tionship and potential mechanisms between NETs and HNSCC.Results MR results indicated a possible causal rela-tionship between NETs and HNSCC.The inverse variance weighted P values for the four datasets were P1=0.037,P2=0.017,P3=0.004,and P4=0.023.Ultimately,52 patients with head and neck squamous cell carcinoma and 20 healthy individuals were included.Compared with the control group,the expression levels of NETs markers MPO-DNA,CitH3,lymph node metastasis markers CD44v6 and CD 109,and coagulation indicators FIB and DD were significantly elevated in the group with head and neck squamous cell carcinoma,with statistically significant differences(all P＜0.001).In cor-relation studies between NETs markers and lymph node metastasis markers,as well as coagulation indicators,the Pear-son correlation coefficient was 0.686,0.531,0.7,and 0.5 for MPO-DNA and DD,FIB,CD44v6,and CD109,respec-tively,and the Pearson correlation coefficient was 0.456,0.503,0.525,and 0.603 for CitH3 and DD,FIB,CD44v6,and CD 109,respectively(P＜0.05).In terms of diagnostic efficacy,the area under the curve(AUC)for MPO-DNA,CitH3,and MPO-DNA+CitH3 in patients with head and neck squamous cell carcinoma was 0.863,0.892,and 0.905,respec-tively,with an increasing AUC of the receiver operating characteristic curve(ROC)in the order mentioned.Levels of MPO-DNA and CitH3 in patients with early-stage head and neck squamous cell carcinoma were(132.4±16.4)ng/mL and(21.3±2.9)ng/mL,respectively,which were lower than those in patients with advanced head and neck squamous cell carcinoma,who had MPO-DNA and CitH3 levels of(199.3±33.1)ng/mL and(26.6±3.7)ng/mL,respectively.The serum concentrations of FIB,DD,CD44v6,and CD109 in patients with high MPO-DNA expression were significantly higher than those in patients with low MPO-DNA expression(all P＜0.05).The serum concentrations of FIB,CD44v6,and CD 109 in patients with high CitH3 expression were significantly higher than those in patients with low CitH3 ex-pression(all P＜0.05).Conclusion The study indicates a potential causal relationship between NETs and HNSCC.NETs-related markers may serve as potential biomarkers for HNSCC,as they correlate with the hypercoagulable state of the cancer.NETs-related markers have potential diagnostic utility for HNSCC and are associated with tumor progres-sion.