不同病理分期肺腺癌患者血清代谢组学研究

肺癌是当今世界最常见的恶性肿瘤之一,其新发率和死亡率多年来都居于各类癌症之首,其中85%的肺癌都是非小细胞癌,而腺癌又是最常见的非小细胞癌。肺癌的高隐匿性是造成其高死亡率的最主要原因,因此为肺癌的早期诊断和病理分期寻求高效可靠的方法是十分必要的。代谢组学揭示了小分子代谢物的一系列变化,反映了生命活动的最终状态,因此也能直接反映疾病不同发展阶段的病理生理变化。本研究利用核磁共振氢谱(1H-NMR),对在我院就诊的27例不同病理分期的肺腺癌患者和13例健康志愿者进行了血清代谢物分析,运用正交偏最小二乘判别分析(OPLS-DA)对1H-NMR数据进行建模,单变量统计分析对模型进行评价。结果表明肺腺癌患者组的血清中有14种代谢物出现明显差异,其中丙酮酸、丙氨酸、NAC1、乳酸、GPC和甘氨酸比起对照组来有显著上升,而葡萄糖、谷氨酰胺、亮氨酸、异亮氨酸、缬氨酸、丙酮、乙酰乙酸和苏氨酸则显著下降。而在不同分期肺腺癌患者间进行比较后发现,异亮氨酸、乙酰乙酸、NAC1和乳酸的变化与肺腺癌的发展有相关性,可能是肺腺癌早期诊断和分期的潜在生物标志物。     

88例女性小细胞肺癌临床特征分析

目的了解女性小细胞肺癌的临床特征分布。方法收集2006年1月至2012年11月大连医科大学附属二院收治的341例小细胞肺癌女性患者88例的临床资料,分析患者在年龄、分期、就诊症状、体重下降、吸烟、家族史、肿瘤位置、治疗方式、疗效反应等方面的特征。结果 2006-2012年该院女性小细胞肺癌住院患者数呈上升趋势;女性患者平均患病年龄为（57.8±11.2）岁,小于同期男性患者（60.4±10.3）岁;女性〈65岁患者比例高于男性患者（73.9%vs 67.5%）,两者比较差异有统计学意义（P=0.018）;女性患者吸烟只有13.6%,远远低于男性患者吸烟比例（85.5%）,两者比较差异有统计学意义（P=0.000）;女性家族史、体重下降、就诊症状、肿瘤位置、分期、疗效以及治疗方式的选择均与男性无差别。在广泛期小细胞肺癌中观察到女性最常见的远处转移是肝转移（40.0%）,男性肝转移只占22.2%,两者比较差异有统计学意义（P=0.036）。结论女性小细胞肺癌数一直呈上升趋势;女性小细胞肺癌就诊的平均年龄小于男性患者;在中青年小细胞肺癌中女性常见;女性吸烟患者较少;相对于男性患者,女性更常见于肝转移。     

血清NSE、SCCA及CEA在肺癌早期诊断和预后预测中的应用价值研究

目的:研究血清神经元特异性烯醇化酶(NSE)、鳞状细胞癌抗原(SCCA)及癌胚抗原(CEA)在肺癌早期诊断和预后预测中的应用价值。方法:选择我院2013年1月~2017年1月收治的110例肺癌患者(肺癌组)及同期96例肺部良性疾病患者(肺良性病组)和85例门诊健康体检者(对照组)。比较各组血清NSE、SCCA及CEA水平,采用受试者工作特征(ROC)曲线分析以上指标对肺癌的诊断价值。结果:肺癌组血清NSE、SCCA、CEA水平高于肺良性病组及对照组,肺良性病组血清NSE、SCCA、CEA水平高于对照组(P<0.05)。肺癌Ⅲ+Ⅳ组血清NSE、SCCA及CEA水平高于Ⅰ+Ⅱ组(P<0.05)。小细胞肺癌组血清NSE水平高于鳞癌组、腺癌组,鳞癌组血清SCCA水平高于腺癌组及小细胞肺癌组,腺癌组血清CEA水平高于鳞癌组及小细胞肺癌组(P<0.05)。NSE<16.0μg/L者平均无疾病进展生存期(PFS)长于NSE≥16.0μg/L,SCCA<1.5μg/L者平均PFS长于SCCA≥1.5μg/L,CEA<5.0μg/L平均PFS长于CEA≥5.0μg/L(P<0.05)。NSE、SCCA和CEA及三者联合诊断肺癌的ROC曲线下面积分别为0.880、0.651、0.830及0.937,NSE+SCCA+CEA联合诊断的曲线下面积高于单个指标单独诊断(P<0.05)。结论:血清NSE、SCCA及CEA对肺癌的诊断有重要的参考价值,且有利于肺癌的分期、分型及预后评价。     

Proteomics analysis of human serum of patients with non-small-cell lung cancer reveals proteins as diagnostic biomarker candidates

Non-small-cell lung carcinomas (NSCLC) is the most common type of lung cancer and it has a poor prognosis, because overall survival after 5 years is 20–25% for all stages. Thus, it is extremely important to increase the survival rate in the early stages NSCLC by focusing on novel screening tests of cancer identifying specific biomarkers expression associated with a more accurate tumor staging and patient prognosis. In this study, we focused our attention on quantitative proteomics of three heavily glycosylated serum proteins: AMBP, α2 macroglobulin, and SERPINA1. In particular, we analyzed serum samples from 20 NSCLC lung adenocarcinoma cancer patients in early and advanced stages, and 10 healthy donors to obtain a relative quantification through the MRM analysis of these proteins that have shown to be markers of cancer development and progression. AMBP, α2 macroglobulin, and SERPINA1 were chosen because all of them possess endopeptidase inhibitor activity and play key roles in cancer. We observe a variation in the expression of these proteins linked to the stage of the disease. Therefore, we believe that proteins like α2 macroglobulin, αmicroglobulin/bikunin, and SERPINA1 could be useful biomarkers for early detection of lung cancer and in monitoring its evolution.     

TUBB3mRNA表达对紫杉醇化疗晚期非小细胞肺癌患者疗效的影响

目的：探讨TUBB3mRNA表达对紫杉醇化疗晚期非小细胞肺癌患者疗效影响。方法：对我院收治的100例晚期非小细胞肺癌患者根据其TUBB3mRNA表达情况将其分为阳性组55例和阴性组45例,对两组患者均采用紫杉醇联合顺铂进行治疗,分析两组患者的临床资料以及预后。结果：两组患者的临床资料无明显差异性,而阴性组患者在客观缓解率、部分缓解率、疾病进展率、总生存时间以及至肿瘤进展时间均优于对照组（P〈0．05）。阳性组在性别、年龄、淋巴结转移、TNM分期的比较中无差异,而在病理分型中（鳞癌／腺癌）的比较中存在显著性差异。结论：TUBB3mRNA阴性表达的患者其采用紫杉醇联合顺铂进行治疗可明显延长患者生存时间。     

PRDM基因与非小细胞肺癌关系的研究现状

肺癌是当今世界上严重威胁人类健康的恶性肿瘤,具有高发病率和高死亡率。目前缺乏理想的早期诊断手段。PRDM基因家族是近年来新发现的与人类肿瘤形成相关的转录调节因子家族,通过启动子区高甲基化参与多种肿瘤形成,并在细胞分化和恶变中发挥重要作用。目前,对于PRDM基因在非小细胞肺癌中作用的研究多集中在PRDM1、PRDM5和PRDM14。本文主要综述了PRDM1、PRDM5和PRDM14在非小细胞肺癌中的表达及其与非小细胞肺癌患者临床特征关系的研究现状。PRDM基因有望成为肺癌的早期诊断和预后评估的新靶点。     

X线片和多层螺旋CT诊断及鉴别周围型肺癌的对比研究

目的:对比X线平片和多层螺旋CT诊断及鉴别周围型肺癌的效果。方法:选取了100例周围型肺癌患者,所有患者入院后先行X线片检查,后进行多层螺旋CT检查。通过观察并记录X线片与多层螺旋CT对周围型肺癌的影像学特征、临床TNM分期的诊断效果,评价X线平片和多层螺旋CT对周围型肺癌的诊断效果。结果:多层螺旋CT对周围型肺癌的肿块、分叶征、支气管气象征、空洞、胸膜凹陷、血管集束征,胸腔积液的检出率均高于X线片(P0.05)。根据外科病理TNM分期结果,多层螺旋CT对周围型肺癌的临床TNM分期诊断符合率为92.0%,X线对周围型肺癌的临床TNM分期诊断符合率为61.0%,多层螺旋CT对周围型肺癌的临床TNM分期诊断符合率明显高于X线(P0.05)。结论:多层螺旋CT对于周围型肺癌各类型影像学征象具有较好的检出率,对周围型肺癌临床TNM分期诊断准确性接近病理诊断结果。     

Apport de la TEP/TDM dans les cancers broncho-pulmonaires : étude d’une série de 35 cas

Lung cancer is one of the most common cancers in Morocco. Currently, PET/CT with FDG is described as the best suited imaging test to evaluate the initial extension of this type of cancer in it non-metastatic variety. Our study confirms the literature data, showing the superiority of PET/CT versus CT in the initial staging of lung non-small cell carcinoma.     

A common genetic variant (97906C>A) of DAB2IP/AIP1 is associated with an increased risk and early onset of lung cancer in Chinese males

DOC-2/DAB2 interactive protein (DAB2IP) is a novel identified tumor suppressor gene that inhibits cell growth and facilitates cell apoptosis. One genetic variant in DAB2IP gene was reported to be associated with an increased risk of aggressive prostate cancer recently. Since DAB2IP involves in the development of lung cancer and low expression of DAB2IP are observed in lung cancer, we hypothesized that the variations in DAB2IP gene can increase the genetic susceptibility to lung cancer. In a case-control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we investigated the association between two common polymorphisms in DAB2IP gene (-1420T>G, rs7042542; 97906C>A, rs1571801) and the risk of lung cancer. We found that compared with the 97906CC genotypes, carriers of variant genotypes (97906AC+AA) had a significant increased risk of lung cancer (adjusted odds ratio [OR] = 1.33, 95%CI = 1.04-1.70, P = 0.023) and the number of variant (risk) allele worked in a dose-response manner (P(trend) = 0.0158). Further stratification analysis showed that the risk association was more pronounced in subjects aged less than 60 years old, males, non-smokers, non-drinkers, overweight groups and in those with family cancer history in first or second-degree relatives, and the 97906A interacted with overweight on lung cancer risk. We further found the number of risk alleles (97906A allele) were negatively correlated with early diagnosis age of lung cancer in male patients (P = 0.003). However, no significant association was observed on the -1420T>G polymorphism. Our data suggested that the 97906A variant genotypes are associated with the increased risk and early onset of lung cancer, particularly in males.     

ERCC1和RRM1在非小细胞肺癌组织中的表达及意义

目的:观察非小细胞肺癌中ERCC1和RRM1表达,并探讨其临床意义。方法:选择本院及西安交通大学第一附属胸外二科于2013年1月-2013年6月收治的经术后病理证实为非小细胞癌肺癌患者40例作为研究对象,均采取免疫组化技术测定组织中ERCC1和RRM1表达水平,并分析ERCC1和RRM1表达水平与患者年龄、病理分期、是否淋巴结转移等相关因素之间的关系。结果:40例非小细胞肺癌患者中,ERCC1表达阴性28例(70.0%),阳性12例(30.0%);RRM1表达阴性9例(22.5%),阳性31例(77.5%)。ERCC1和RRM1表达阴性非小细胞肺患者生存期均优于表达阳性患者,均P0.05。患者非小细胞癌TNM分期及淋巴结转移转移情况与ERCC1及RRM1表达情况具有相关性,均P0.05。结论:非小细胞肺癌ERCC1和RRM1表达水平测定有助于预后情况,具有重要临床价值。     

Rapid KRAS, EGFR, BRAF and PIK3CA mutation analysis of fine needle aspirates from non-small-cell lung cancer using allele-specific qPCR

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS-TBNA) and Trans-esophageal Ultrasound Scanning with Fine Needle Aspiration (EUS-FNA) are important, novel techniques for the diagnosis and staging of non-small cell lung cancer (NSCLC) that have been incorporated into lung cancer staging guidelines. To guide and optimize treatment decisions, especially for NSCLC patients in stage III and IV, EGFR and KRAS mutation status is often required. The concordance rate of the mutation analysis between these cytological aspirates and histological samples obtained by surgical staging is unknown. Therefore, we studied the extent to which allele-specific quantitative real-time PCR with hydrolysis probes could be reliably performed on EBUS and EUS fine needle aspirates by comparing the results with histological material from the same patient. We analyzed a series of 43 NSCLC patients for whom cytological and histological material was available. We demonstrated that these standard molecular techniques can be accurately applied on fine needle cytological aspirates from NSCLC patients. Importantly, we show that all mutations detected in the histological material of primary tumor were also identified in the cytological samples. We conclude that molecular profiling can be reliably performed on fine needle cytology aspirates from NSCLC patients.     

Mechanisms involved in lung cancer development in COPD

Lung cancer and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality worldwide. They share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by the incidence of these diseases in only a fraction of smokers. COPD is also a major independent risk factor for lung carcinoma, among long-term smokers. Smokers with COPD also have a higher risk of developing a specific histological subtype of non-small cell lung cancer termed squamous cell carcinoma. For these reasons the focus of this review is on the potential pathogenic molecular links between tobacco smoking-related COPD and squamous cell carcinoma. We believe that we need to promote more studies on the molecular and cellular pathobiology of smokers with premalignant bronchial lesions of the squamous cell lung carcinoma compared with a control group of smokers with and without COPD to unravel the complex molecular interactions between COPD and early squamous cell lung carcinoma. These studies should also look at younger healthy smokers in combination with risk models of lung cancer and COPD. Overall these studies may allow the discovery of new molecular targets of the early carcinogenesis process that in the foreseeable future may render the early diagnosis and treatment, and may be even the prevention, of invasive squamous cell lung carcinoma a reality.     

Screening for lung cancer.

The survival from bronchogenic carcinoma is highly dependent upon stage at the time of treatment. This is particularly true for squamous cell carcinoma, adenocarcinoma, and large cell carcinoma, but holds true for small cell carcinoma as well. The problem presented to the medical profession has been to find a practical means of detecting lung cancer while it is still at an early stage. Three studies in progress have indicated that a larger proportion of the patients may be found to have early stage lung cancer when screened with a combination of chest X-rays and sputum cytology. However, the detection of these early stage cases has not yet been translated into an improvement in the overall mortality rate from lung cancer.     

多胺代谢与癌肿的研究

研究多胺与癌肿的关系。这些癌肿包括Raji癌肿细胞 ,急性淋巴细胞白血病 ,妇产科癌肿 (卵巢癌等 ) ,卵巢癌HO— 891 0细胞 ,肺癌以及胃癌等。研究结果 :(1 )Raji癌细胞株及卵巢癌细胞株 (HO— 891 0 )在培养过程中 ,第 2 4～4 8h多胺水平出现高峰 ,它与这两种癌细胞的核酸合成 ,细胞增殖呈现正相关 ;(2 )急性淋巴细胞白血病患者淋巴细胞及红细胞中多胺水平均升高 ,这有助于对这些病的早期诊断及判断预后 ;(3 )妇科癌症 (尤其卵巢癌 ) ,肺癌 ,胃癌等患者尿液中多胺水平明显高于正常 ,所以尿液中多胺对这些癌肿也是一种有效的诊断标记物     

Early CYFRA 21-1 variation predicts tumor response to chemotherapy and survival in locally advanced non-small cell lung cancer patients

We have evaluated CYFRA 21-1 serum level variations as an indicator of tumor response and survival in 44 consecutive patients with locally advanced non-small cell lung cancer (NSCLC) treated with induction chemotherapy (IC). Irrespective of the initial CYFRA 21-1 serum concentration, a more than 65% decrease in the serum level after the first chemotherapy course was significantly predictive of an objective tumor response (p = 0.0022). In addition, a more than 80% decrease in this level significantly predicted a better disease-free survival (p = 0.039). In patients with initial CYFRA 21-1 serum levels > 3.3 ng/mL (n = 29), a more than 80% decrease after the first IC course was the most significant predictor of overall survival (p = 0.025) in a Cox analysis including initial staging, tumor response and surgery. We conclude that early monitoring of CYFRA 21-1 serum levels may be a useful prognostic tool for tumor response and survival in stage III NSCLC patients treated by induction chemotherapy.     

Cathepsin D is secreted from M-BE cells: its potential role as a biomarker of lung cancer

The early diagnosis of lung cancer is an effective approach to reduce the mortality caused by malignancy. To explore serum biomarkers of lung cancer at early stage, M-BE, a SV40T-transformed human bronchial epithelial cell line with the phenotypic features of early tumorigenesis at high passage, was cultured in the conditioned media to collect its secretory proteins. The proteins secreted from different passage M-BE cells were extracted and then separated by two-dimensional electrophoresis (2-DE). MALDI-TOF/TOF mass spectrometry was adopted to identify the passage-dependent 2-DE spots. Totally, 47 proteins were identified, including 23 that were up-regulated and 24 that were down-regulated. Of these proteins, cathepsin D was a typical secretory protein that exhibited the increased abundance either in culture media or in cells during passaging. Furthermore, the proteomic conclusions were validated in the clinical samples of lung cancer patients. When sandwich ELISA was used, the concentrations of cathepsin D in plasma showed significant differences between lung squamous cell carcinomas (SCC, 104 cases) and normal donors (36 cases, p 相似文献   

Cost-effective PET investigations in oncology

The authors have reviewed the financial considerations of oncological FDG PET examinations by the guidelines of the Health Care Financing Administration (USA). By critical assessment of large number of clinical investigations,the cost-effectiveness of FDG PET scans has been confirmed in the following cases: differential diagnosis of solitary pulmonary nodule, diagnosis,staging and restaging of non-small cell lung cancer, colorectal cancer, malignant lymphomas, melanoma malignum, esophageal neoplasms and cancers of the head and neck. The role of this method in breast cancer is currently under intensive investigation. Due to the correct staging, PET examinations in these indications enable the clinicians to choose the optimal treatment ensuring the maximum probability of recovery and being cost-effective as unnecessary medical interventions become avoidable.     

磁共振扩散加权成像在肺癌中的临床应用

影像学检查在肺癌的诊断和分期中起到了至关重要的作用,目前电子计算机体层成像(CT)和正电子发射断层成像技术以及磁共振成像(MRI)已经被广泛的应用于肺癌的分期和疗效评估。其中MRI不仅能提供形态学信息,近年来发展起来的磁共振功能成像能提供更多的功能信息。磁共振扩散加权成像(Diffusion-weighted imaging,DWI)是最常应用于临床的磁共振功能成像序列。最初主要应用在神经系统,随着磁共振成像序列的不断发展以及软硬件的开发应用,其在腹部和盆腔的应用也日趋广泛,然而胸部DWI成像仍待普及和更多认识。本文就肺部DWI成像在良恶性病变鉴别、恶性肿瘤的筛查、分期、以及治疗疗效评估方面进行综述。     

Nicotine prevents the apoptosis induced by menadione in human lung cancer cells

Approximately 50% of long-term cigarette smokers die prematurely from the adverse effects of smoking, including on lung cancer and other illnesses. Nicotine is a main component in tobacco and has been implicated as a potential factor in the pathogenesis of human lung cancer. However, the mechanism of nicotine action in the development of lung cancer remains largely unknown. In the present study, we designed a nicotine-apoptosis system, by pre-treatment of nicotine making lung cancer cell A549 to be in a physiological nicotine environment, and observed that nicotine promoted cell proliferation and prevented the menadione-induced apoptosis, and exerts its role of anti-apoptosis by shift of apoptotic stage induced by menadione from late apoptotic stage to early apoptotic stage, in which NF-kappaB was up-regulated. Interference analysis of NF-kappaB in A549 cells showed that knock down of NF-kappaB resulted in apoptosis promotion and counteracted the protective effect of nicotine. The findings suggest that nicotine has potential effect in lung cancer genesis, especially in patients with undetectable early tumor development and development of specific NF-kappaB inhibitors would represent a potentially exciting new pharmacotherapy for tobacco-related lung cancer.