非小细胞肺癌患者三项肿瘤标识物联合检测的意义

目的:研究非小细胞肺癌(NSCLC)及肺部良性疾病患者血清癌胚抗原(CEA)、细胞角蛋白质19片段(CYFRA21-1)和SCC的水平,探讨联合检测在诊断中的价值。方法:检测70例NSCLC患者和20例良性肺疾病患者血清中CEA、CYFRA21-1和SCC的水平。结果:NSCLC组血清CEA、CYFRA21-1和SCC的测定值均高于肺良性病变组(P<0.05),并且与病理类型有关。CEA的血清浓度水平与肿瘤的分期有关。三项肿瘤标记物联合检测的敏感性为87.1%,优于单项检测。结论:CEA、CYFRA21-1和SCC的联合检测可以提高对NSCLC的诊断水平,有助于对病情和预后的判断。     

基于临床病理特征富集初治NSCLC患者EGFR基因突变的相关研究

目的分析初治非小细胞肺癌（non-small cell lung cancer,NSCLC）患者肺原发灶EGFR（epidermal growth factor receptor,EGFR）基因突变状态与临床病理特征的相关性,为临床EGFR—TKIs（tyrosine kinase inhibitors,TKIs）用药提供依据。方法收集第三军医大学附属大坪医院应用增殖阻遏突变系统（amplification refractory mutation system,ARMs）进行EGFR突变分析253例初治非小细胞肺癌患者的性别、年龄、吸烟史、KPS（Karnofsky performance status,KPS）评分、组织病理类型、TNM临床分期以及伴有脑转移患者的脑转移灶数量、确诊肺癌至诊断脑转移时间（brain metastasis time from diagnosis of lungcancer,BMT）和颅外转移状况等临床病理资料,应用x。检验分析EGFR突变状态与各临床病理特征的关系。结果253例初治NSCLC患者,EGFR基因敏感型突变率42．3％（107／253）,其中EGFR基因第19、21外显子突变比例分别为70．1％（75／107）、39．1％（32／107）,而EGFR基因20外显子TKIs耐药型突变率0．8％（2／253）。女性、无吸烟史、腺癌的肺原发灶EGFR基因敏感型突变率明显高于男性、有吸烟史、非腺癌患者,分别为70．2％（66／94）VS25．8％（41／61）、60．9％（81／133）VS18．1％（19／105）和50．0％（103／206）vs8．5％（4／47）,两者有显著性差异（P〈O．05）。结论初治NSCLC患者肺原发灶存在较高（42．3％）EGFR基因敏感型突变,其中女性、腺癌、无吸烟史NSCLC患者EGFR基因敏感突变显著多见。     

eIF-4E基因在非小细胞肺癌中的表达及与化疗敏感性的关系

目的探讨e IF-4E基因在非小细胞肺癌(Non small cell lung cancer,NSCLC)表达及与化疗敏感性的关系。方法选用外科手术切除NSCLC组织60例以及癌旁正常组织30例作为对照,通过免疫组化检测癌组织以及正常肺组织中el F-4E的表达。NSCLC患者术后接受榄香烯顺铂治疗至少两周以上。比较el F-4E在癌组织以及正常肺组织中的表达、e IF-4E阴性表达患者和阳性表达患者的总生存期和化疗效果。结果 e IF-4E在NSCLC患者癌组织中的阳性表达率显著高于癌旁组织(P<0.01);e IF-4E阴性表达患者的OS较阳性患者明显延长,阳性表达患者的化疗完全缓解率亦显著低于e IF-4E阴性表达患者(P<0.01)。结论 e IF-4E可能成为NSCLC诊断的标志物,e IF-4E表达水平检测可用于NSCLC患者个体治疗方案的选择。     

Bone metastases in non-small cell lung cancer: a narrative review

Background and ObjectiveBone metastases are common in patients with non-small cell lung cancer (NSCLC) and remain a significant source of morbidity, mortality, and diminished quality of life, despite the considerable progress made in the overall management of patients with metastatic NSCLC over the last decade. Understanding the molecular pathogenesis of bone metastases is critical to improving survival, preserving function, and managing symptoms in this patient population. The objective of our review is to provide a comprehensive review of the pathophysiology, clinical presentation, management, and factors predicting the development and prognosis of patients with NSCLC with bone metastases.MethodsAn online electronic search was performed on PubMed and Google Scholar of all English-language literature using combinations of the following keywords: bone metastases, non-small cell lung cancer, pathophysiology, skeletal related events, response to therapy, predictive factors, and immunotherapy. Bibliographies of identified papers were reviewed for additional articles of interest. Observational cohort, retrospective studies, randomized controlled trials (RCTs), meta-analyses, and review articles were examined for this review.Key Content and FindingsBone metastases in lung cancer patients remain a common occurrence, impacting morbidity, mortality, and quality of life. Patients with skeletal related events (SREs) have worse prognosis. There is data supporting use of bisphosphonates and/or denosumab, and these should be considered in all patients with bone metastases. Novel studies comparing the genomic alterations of skeletal metastases and primary tumors are needed. As therapy for patients with advanced disease evolves, more studies are needed to evaluate the interplay between immunotherapy and bone metastases, and in determining the response to treatment in bone.ConclusionsPredicting development and progression of bone metastases could allow earlier and targeted therapy in patients with bone metastases. Predicting and evaluating response to conventional chemotherapy and immune checkpoint inhibitors in NSCLC patients with bone metastases remains an unmet need and merits further study.     

Prognostic value of selected platelet parameters of patients operated for non-small cell lung cancer

BackgroundPlatelets play a vital role in the neoplastic process. Platelet parameters are hence an important source of information concerning ongoing neoplastic disease. The aim of the study is to assess the impact of selected platelet parameters on the survival of patients with non-small cell lung cancer (NSCLC).MethodsThe study included 532 (174 female and 358 male) patients aged 36–84 years (mean age 63.6 years) operated on due to NSCLC, staged IA–IIIA. Before the operation, all patients received a blood morphology test. The following parameters were subjected to statistical analysis: platelet count, mean platelet volume (MPV) parameter, platelet distribution width (PDW) parameter, platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation (SII) index. These findings were compared with the clinical data of the patients, and the probability of overall survival was analyzed.ResultsThe univariate analysis revealed a correspondence between PDW, MPV, PLR and SII index and patient survival. The multivariate analysis including patient clinical data found the following factors to have negative prognostic value for patients operated on due to NSCLC: male sex, advancement stage of neoplastic disease and Charlson Comorbidity Index (CCI) above 4, and PLR >144.ConclusionsPDW value, PLR and SII index are independent prognostic factors. In the multi-factor model, male sex, the advancement stage of the neoplastic disease, CCI above 4 and PLR lower than 144 had the greatest prognostic value.     

Efficacy of dacomitinib in patients with non-small cell lung cancer carrying complex EGFR mutations: a real-world study

BackgroundDacomitinib is a first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations; however, clinical evidence of its activity on NSCLC with complex EGFR mutations is limited.MethodsPatients harboring complex (common mutations co-existing with uncommon mutations), or common (comparison cohort) EGFR mutations, who were treated with dacomitinib, were retrospectively evaluated in the Chinese National Cancer Center and the China PLA hospital between August 2019 and August 2021.ResultsIn total, 72 patients with NSCLC harboring complex (C+U group, n=18) or common (C group, n=54) EGFR mutations and being treated with dacomitinib were enrolled. In the C+U group, 16 cases (88.9%) harbored L858R mutations co-existing with uncommon mutations located from exon 18 to exon 25 of EGFR (mostly E709X), and two cases harbored exon 19 deletion co-existing with G724S or K754E. Among the 15 evaluable patients, the objective response rate (ORR) was 40% (6/15), and the disease control rate (DCR) was 73.3% (11/15). The median progression-free survival (PFS) was 7.5 months [95% confidence interval (CI), 4.4–10.6 months]. Except for the application line of dacomitinib (P=0.039), no significant statistical differences were found in other characteristics and adverse events between the two groups. The Kaplan-Meier method revealed no significant differences in PFS (P=0.889) and overall survival (OS) (P=0.703). However, the stratified analysis found worse PFS in the C+U group than that observed in the C group when receiving 1^st and ≥3^rd line dacomitinib treatment, while its OS was worse than that of group C when receiving ≥3^rd line treatment. Furthermore, in a multivariate analysis, complex mutation status was an independent prognostic factor for OS (P=0.038) in the entire cohort.ConclusionsThis study indicated a worse response and prognosis of patients with NSCLC harboring complex EGFR mutations than those harboring common EGFR mutations when treated with dacomitinib. Further studies and data are needed to confirm this conclusion.     

IL-17和MMP-9在非小细胞肺癌中的表达及临床意义

目的探讨白细胞介素-17(IL-17)和基质金属蛋白酶-9(MMP-9)在非小细胞肺癌患者癌组织中的表达及其临床意义。方法对经随诊资料完整的术后非小细胞肺癌(NSCLC)患者组织标本60例,采用PV9000二步免疫组化法检测IL-17和MMP-9在癌组织及癌旁组织中的表达。结果 IL-17、MMP-9在非小细胞肺癌组织中表达的阳性率为78.3%、80.0%,在癌旁组织中表达阳性率分别为48.3%、35.0%,癌组织中IL-17与MMP-9的表达高于癌旁组织(P<0.05);不同年龄、性别、病理类型及分化程度的患者其IL-17表达无明显差异(P>0.05);IL-17和MMP-9的阴性表达的患者其3a生存期高于阳性表达组,差异有统计学意义(P<0.05)。结论 IL-17和MMP-9的高表达对非小细胞肺癌的侵袭和转移起着重要作用;IL-17和MMP-9的高表达是肺癌预后不良的指标。     

Livin、Survivin蛋白在非小细胞肺癌胞核中的表达及意义

目的研究凋亡抑制蛋白Survivin和Livin在tPA,细胞肺癌（NSCLC）细胞核中阳性表达（核阳）水平及其临床意义。方法采用免疫组织化学sP法检测40例NSCLC组织和20例癌旁正常肺组织中Survivin蛋白和Livin蛋白核阳水平。并分析其与临床特征的关系。结果在NSCLC和癌旁正常肺组织中,Survivin蛋白细胞核表达的阳性率分别为80％（32／40）和5％（1／20）,Livin蛋白细胞核表达的阳性率分别为80％（32／40）和10％（2／20）。Survivin蛋白和Livin蛋白核阳在NSCLC组织中的表达显著高于癌旁组织（P〈0．05）。Survivin蛋白核阳与淋巴结转移、肿瘤分期高度相关（尸〈0．05）。结论Survivin蛋白和Livin蛋白在NSCLC细胞核中高表达,可能成为NSCLC诊断的新指标和治疗的潜在靶点。     

γ-catenin、c-Myc和VEGF在非小细胞肺癌中的表达及其意义

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)病理组织中γ-选择素(γ-catenin/Plakoglobin)、原癌蛋白c-Myc和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达及其与患者预后的关系。方法应用免疫组化方法测定57例NSCLC和14例肺部良性病变病理切片中γ-catenin、c-Myc和VEGF的表达,并对γ-catenin、c-Myc和VEGF的表达与患者的性别、年龄、瘤体大小、病理类型、组织分化程度、临床分期、淋巴结转移情况及生存时间进行统计分析。结果 57例NSCLC中γ-catenin异常表达率和c-Myc的过度表达率分别为66.67%和64.91%,VEGF的阳性表达率为77.19%;14例肺部良性病变均未见γ-catenin的异常表达和c-Myc的过度表达,VEGF有3例为"±"。γ-catenin的异常表达和c-Myc的过度表达有显著相关性,c-Myc的过度表达和VEGF的阳性表达有显著相关性。γ-catenin的异常表达与肿瘤的分化程度及淋巴结转移有关(P0.05);c-Myc的过度表达与瘤体大小及淋巴结转移有关(P0.05);VEGF的阳性表达与瘤体大小及淋巴结转移有关(P0.05),而与在不同临床分期及病理类型之间无统计学意义(P0.05)。结论检测γ-catenin、c-Myc和VEGF在NSCLC中的表达变化是判断恶性肿瘤程度、浸润转移的有效参考指标,γ-catenin异常表达和c-Myc的过度表达可能影响NSCLC患者的预后。     

早期非小细胞肺癌体部立体定向放疗基础和临床研究——不同照射剂量联合吉非替尼对肺癌细胞系H358的影响

目的：探讨不同剂量单纯照射及照射联合吉非替尼对非小细胞肺癌细胞系 H358存活率、增敏比及细胞凋亡、细胞周期的影响。方法体外培养肺腺癌细胞 H358分为空白对照组、单纯照射组、单纯吉非替尼（Iressa）组、照射＋Iressa组,照射剂量为0、2、4、6、8、12、16、20 Gy,药物浓度为1μmol/L。通过细胞克隆形成实验,观察4组 H358细胞存活情况,描绘细胞存活曲线;采用四噻唑比色试验（MTT）观察两组细胞生长受抑制情况,计算增敏比（SER）;运用流式细胞仪检测细胞凋亡率和细胞周期。结果（1）随着照射剂量增加细胞存活分数减小,单纯照射组单次剂量达到20 Gy时,细胞克隆集落形成率为0,照射＋Iressa组单次剂量达到16 Gy时克隆集落形成率为0;（2）照射＋Iressa 组与单纯照射组相比,两组 OD 值差异有统计学意义（F剂量＝62．644,P ＜0．001,F药物＝233．572,P ＜0．001）,两组 OD值随着照射剂量的增高而减小,不同剂量之间 OD值差异有统计学意义（F未加药＝354．972,P＜0．001;F加药＝231．740,P ＜0．001）,两组细胞放射增敏比（SER）与药物显著相关（P ＜0．001）,照射＋Iressa组SER较单纯照射组明显增高;（3）随着照射剂量的增加,凋亡率增高（P ＜0．001）,H358细胞凋亡率与Iressa药物作用相关（P ＜0．001）,单纯Iressa作用后细胞周期阻滞主要出现在G0/G1期,照射＋Iressa组及单纯照射组主要出现G2/M期阻滞。结论增加单次照射剂量可降低 H358细胞存活率,细胞凋亡与 Iressa药物之间存在相关性,照射＋Iressa能够增加细胞凋亡率,照射前使用Iressa能够增强照射对细胞的放射敏感性。