【作者】 李媛；

【导师】 钱东华；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2023， 硕士

【摘要】 背景:肺癌是全球范围内最常见的癌症之一,具有发病率高、诊断晚、预后差、死亡率高等特点。慢性炎症与肺癌的关系是近年来的研究热点,许多研究表明中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、纤维蛋白原与白蛋白比值(FAR)等指标对多种实体肿瘤的诊断及预后有一定的价值,但其与肺癌患者临床病理特征相关性的研究较少。目的:本研究主要探讨NLR、PLR、FAR与肺癌患者临床病理特征的关系及联合肿瘤标志物在非小细胞肺癌(NSCLC)分期中的临床价值。方法:选取2018年7月至2022年9月于吉林大学第一医院明确诊断为肺癌且未进行任何治疗的205例患者,通过电子病案系统回顾性收集其一般资料(年龄、性别、吸烟史)、实验室检验(外周血中性粒细胞计数、外周血淋巴细胞计数、外周血血小板计数、白蛋白值、纤维蛋白原值、癌胚抗原(CEA)、糖类抗原125(CA125))、影像学检查(肺部、腹部、颅脑CT、全身骨显像或PET-CT)、组织病理类型及基因检测结果。依照国际抗癌联盟(UICC)第八版肺癌TNM分期系统对患者进行临床分期,且基于上述实验室检验结果,计算出NLR、PLR及FAR值。本研究使用SPSS26.0软件进行数据分析,先全面比较分析NLR、PLR、FAR与肺癌患者临床病理特征的关系,再进一步分析在肺腺癌患者中其与EGFR基因突变的关系,最后,将NSCLC患者分为I-III期和IV期两组,比较两组间外周血NLR、PLR、FAR和肿瘤标志物CEA、CA125水平,并利用ROC曲线分析上述指标单独及联合检测对IV期NSCLC的诊断效能。结果:1.有远处转移的肺癌患者NLR水平高于无远处转移的肺癌患者,有浆膜腔积液的肺癌患者NLR水平高于无浆膜腔积液的肺癌患者,以上差异均有统计学意义(P<0.05)。在不同临床分期的肺癌患者中NLR水平有显著差异(P<0.05)。2.女性肺癌患者PLR水平高于男性肺癌患者,不吸烟的肺癌患者PLR水平高于吸烟的肺癌患者,有远处转移的肺癌患者PLR水平高于无远处转移的肺癌患者,有浆膜腔积液的肺癌患者PLR水平高于无浆膜腔积液的肺癌患者,以上差异均有统计学意义(P<0.05)。在不同临床分期的肺癌患者中PLR水平有显著差异(P<0.05)。3.吸烟的肺癌患者FAR水平高于不吸烟的肺癌患者,有浆膜腔积液的肺癌患者FAR水平高于无浆膜腔积液的肺癌患者,以上差异均有统计学意义(P<0.05)。FAR水平在不同临床分期及不同浸润程度组间均有显著差异(P<0.05)。4.I-III期与IV期NSCLC患者外周血NLR、PLR及肿瘤标志物CEA、CA125之间的差异有统计学意义(P<0.05),且处于IV期的NSCLC患者值更高。5.利用ROC曲线分析各单项指标对诊断IV期NSCLC患者的最佳截断值分别为NLR 2.41,PLR 146.47,CEA 8.79ng/ml,CA12523.91U/ml;诊断灵敏度分别为PLR(68.2%)>NLR(67.0%)>CA125(55.0%)>CEA(51.8%);诊断特异度分别为:CEA(90.6%)>CA125(75.6%)>PLR(60.5%)>NLR(57.0%)。6.利用ROC曲线分析不同指标联合对IV期NSCLC患者诊断的价值结果提示NLR+PLR+CEA+CA125四项指标联合检测时AUC最大,为0.776,所对应的灵敏度为68.8%,特异度为76.9%;就灵敏度而言,NLR+CEA联合最高,为88.2%;就特异度而言,NLR+CEA+CA125最高,为91.0%。结论:1.NLR、PLR及FAR水平与肺癌患者的临床特征有关,上述指标升高对肺癌进展有提示意义。2.在NLR、PLR、CEA及CA125水平,IV期NSCLC患者较IIII期NSCLC患者高,外周血NLR、PLR及肿瘤标志物CEA、CA125单独或不同指标联合检测对NSCLC患者的临床分期有一定的价值。更多还原

【Abstract】 Background:Lung cancer is one of the most common cancers worldwide,characterized by high incidence,late diagnosis,poor prognosis and high mortality.The relationship between chronic inflammation and lung cancer has been a research hotspot in recent years.Many studies have shown that neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),fibrinogen to albumin ratio(FAR)and other indicators are of certain value in the diagnosis and prognosis of a variety of solid tumors,but there are few studies on their correlation with clinicopathologic characteristics of lung cancer patients.Objective:This study was aimed to investigate the relationship between NLR,PLR,FAR and clinicopathologic features of lung cancer patients and the clinical value of combined tumor markers in the staging of non-small cell lung cancer(NSCLC).Methods:A total of 205 patients who were diagnosed with lung cancer without any treatment in the First Hospital of Jilin University from July 2018 to September 2022 were selected.General data(age,gender,smoking history),laboratory tests(peripheral neutrophil count,peripheral lymphocyte count,peripheral platelet count,albumin value,fibrinogen value,carcinoembryonic antigen(CEA),carbohydrate antigen 125(CA125)),imaging examinations(lung,abdominal,craniocerebral CT,Whole body bone imaging or PET-CT),histopathologic type and genetic test results.Patients were clinically staged according to the TNM staging system of the eighth edition of the International Union Against Cancer(UICC),and NLR,PLR and FAR values were calculated based on the results of the above laboratory tests.In this study,SPSS26.0 software was used for data analysis.Firstly,the relationship between NLR,PLR,FAR and clinicopathologic features of lung cancer patients was comprehensively analyzed,and then the relationship between NLR,PLR,FAR and EGFR gene mutation in lung adenocarcinoma patients was further analyzed.Finally,NSCLC patients were divided into stage I-III and stage IV groups,and the levels of peripheral blood NLR,PLR,FAR and tumor markers CEA and CA125 were compared between the two groups.ROC curve was used to analyze the diagnostic efficacy of the above indexes in stage IV NSCLC alone and in combination.Results:1.The level of NLR in lung cancer patients with distant metastases was higher than that in lung cancer patients without distant metastases,and the level of NLR in lung cancer patients with serous cavity effusion was higher than that in lung cancer patients without serous cavity effusion,with statistical significance(P<0.05).There were significant differences in the level of NLR in lung cancer patients with different clinical stages(P<0.05).2.The PLR level of female lung cancer patients is higher than that of male lung cancer patients;the PLR level of non-smoking lung cancer patients is higher than that of smoking lung cancer patients;the PLR level of lung cancer patients with distant metastasis is higher than that of patients without distant metastasis;the PLR level of lung cancer patients with serous effusion is higher than that of patients without serous effusion.The above differences were statistically significant(P<0.05).There were significant differences in PLR levels in lung cancer patients with different clinical stages(P<0.05).3.The FAR level of lung cancer patients with smoking was higher than that of non-smoking lung cancer patients,and the FAR level of lung cancer patients with serous cavity effusion was higher than that of lung cancer patients without serous cavity effusion,the above differences were statistically significant(P<0.05).There were significant differences in the level of FAR among different clinical stages and different degrees of infiltration(P<0.05).4.There were statistically significant differences in peripheral blood NLR,PLR and tumor markers CEA and CA125 in patients with stage I-III and IV NSCLC(P<0.05),and the values were higher in patients with stage IV NSCLC.5.ROC curve was used to analyze the optimal cut-off values of each i ndex for the diagnosis of stage IV NSCLC patients,which were NLR 2.41,PLR 146.47,CEA 8.79ng/ml and CA125 23.91U/ml,respectively.The d iagnostic sensitivity was PLR(68.2%)>NLR(67.0%)>CA125(55.0%)>CE A(51.8%).The difference of diagnosis was CEA(90.6%)>CA125(75.6%)>PLR(60.5%)>NLR(57.0%).6.ROC curve was used to analyze the diagnostic value of different indexes combined with stage IV NSCLC patients.The results indicated that the combined AUC value of NLR+PLR+CEA+CA125 was the largest,which was 0.776,with the corresponding sensitivity of 68.8% and specificity of 76.9%.In terms of sensitivity,NLR+CEA combined with the highest,88.2%;In terms of specificity,NLR+CEA+CA125 was the highest(91.0%).Conclusions:1.The levels of NLR,PLR and FAR are related to the clinical characteristics of patients with lung cancer,and the increase of the above indexes has suggestive significance for the progression of lung cancer.2.The levels of NLR,PLR,CEA and CA125 in stage IV NSCLC patients are higher than those in stage I-III NSCLC patients,and the detection of peripheral blood NLR,PLR and tumor markers CEA and CA125 alone or combined with different indexes is of certain value for the clinical staging of patients with NSCLC.更多还原