肺癌肿瘤标记物的研究进展

近年来随着分子生物学技术的不断发展 ,肿瘤标记物方面的研究相当活跃 ,在临床上 ,已被广泛应用于肿瘤的诊断、评估疗效、监测复发和推测预后。本文就这方面的应用及进展综述如下。1　单一检测1.1　细胞角蛋白 19片段 :细胞角蛋白 19段 (ＣＹＦＲＡ2 1- 1)是采用夹心酶联免疫吸附法 ,联合应用两种特异性单克隆抗体 (Ｋｓ19.1和ＢＭ19.2 1)进行检测血清中的细胞角蛋白19片段。细胞角蛋白是细胞体的中间丝 ,根据其分子量和双向二维电泳中等电点的不同 ,可以分为 2 0种不同类型。其中 ,ＣＹＦＲＡ2 1- 1在肺癌中含量尤其丰富。1994年Ｋｏｇａ等…     

肺癌多项肿瘤标记物联合检测及临床意义

用生物化学、免疫化学和放射免疫方法,对70例肺癌、24例肺结核、20例肺心病患者及61名正常人进行了8项血清肿瘤标记物检测;并利用电子计算机对检测结果进行了逐步判别分析,探讨各肿瘤标记物在肺癌辅助诊断方面的意义。结果,肺癌 LSA、α_1-AG、α_1-AT、β_2-MG、SF 和 IgMCIC 水平升高,EA 光密度增加;肺结核α_1-AT、β_2-MG、SF、IgG 和 IgMCIC 水平也升高;肺心病α_1-AT、β_2-MG 及 SF 水平升高。肺癌手术和化学治疗后 LSA 降低。未分化小细胞肺癌 IgMCIC 水平高于肺鳞癌。肺癌 CIC 以 IgMCIC 为主。逐步判别分析结合综合判断分析后的数据提示,联合检测 EA、LSA、α_1-AT 及 SF 对肺癌的辅助诊断价值较大。     

血清肿瘤标记物系列检测对肺癌的临床诊断价值

目的 评价血清肿瘤标记物癌胚抗原（CEA）、癌抗原125（CA125）、糖原19-9（CA19-9）、细胞角蛋白19片断（CYFRA21-1）、神经元特异性烯醇化酶（NSE）、肿瘤相关物质（TSGF）检测对肺癌的临床诊断价值。方法 应用日本产Elecsys 2010，采用化学发光免疫测定法，检测138例未经治疗的初诊肺癌患者（肺癌组）的血清CEA、CA125、CA19-9、CYFRA21-1、NSE和TSGF水平；另选择100例肺良性疾病患者（对照组1）和50名健康人（对照组2）作为对照。结果 肺癌组血清CEA、CA125、CA19-9、CYFRA21-1、NSE和TSGF中位水平明显高于对照组1、2（均P〈0.01）．对照组1与对照组2比较差异无显著性意义（P〉0．05）。当特异性为100％．若血清CEA≥16ng／ml、CA125≥47U／ml，CA19-9≥47U／ml、CYFRA21-1≥8ng／ml、NSE ≥20ng／ml、TSGF≥65U／ml，诊断肺癌的敏感性分别为43％、42％、26％、55％、19％和28％；6项联合检测的敏感性（78％）较单项检测高（P〈0．01）。细胞学（痰、和／或纤维支气管镜毛刷、和/或细针肺穿刺）检查的敏感性为66％（91／138）。较6项血清肿瘤标记物联合检测的敏感性低（P〈0．05）；细胞学联合血清肿瘤标记物系列测定，其敏感性为84％（116／138），提高了18％（P〈0.01）。另外，CYFRA21-1在鳞癌的敏感性（67％）最高（P〈0．01），CA125在腺癌（65％）最高（P〈0．01）。结论 血清肿瘤标记物系列检测能辅助诊断肺癌。     

血清肿瘤标记物联合检测在肺癌诊断中的应用价值

肺癌是临床上最常见的恶性肿瘤之一[1],能够早期发现、并及时治疗是医治关键。而临床实践显示：肺癌确诊时多为中、晚期而延误治疗,开胸取活检做病理检查创伤大,又易引起并发症[2],所以给肺癌的早期诊断带来了不便。     

6种血清肿瘤标记物的联合检测在肺癌诊断中的应用价值

目的 联合检测CEA、NSE、CYFRA21-1、TPA、CA15-3、CA242等6种血清肿瘤标记物水平,探讨其在肺癌临床诊断中的应用价值.方法 应用放射免疫法和酶联免疫法分别检测试验组(98例肺癌患者)和对照组(35例肺良性病患者,45例健康体检者)血清中CEA、NSE、CYFRA21-1、TPA、CA15-3、CA242等6种血清肿瘤标记物水平,并采用t检验对数据结果进行统计学分析.结果 实验组血清中的6项肿瘤标记物含量均高于对照组;肿瘤标记物水平还与病理类型有关,CEA、CA15-3、CA242以肺腺癌中最高,NSE以肺小细胞癌中最高,CYFRA21-1、TPA以肺鳞癌中最高;血清肿瘤标记物联合检测上述三种肺癌的阳性率显著升高,分别达到100%、96.0%、97.8%.结论 6种肿瘤标记物对于肺癌的诊断有临床价值,并便于确定病理类型,且联合检测可以提高肺癌诊断的敏感性,大大提高肺癌的检出率.     

6种血清肿瘤标记物的联合检测在肺癌诊断中的应用价值

目的 联合检测CEA、NSE、CYFRA21-1、TPA、CA15-3、CA242等6种血清肿瘤标记物水平,探讨其在肺癌临床诊断中的应用价值.方法 应用放射免疫法和酶联免疫法分别检测试验组(98例肺癌患者)和对照组(35例肺良性病患者,45例健康体检者)血清中CEA、NSE、CYFRA21-1、TPA、CA15-3、CA242等6种血清肿瘤标记物水平,并采用t检验对数据结果进行统计学分析.结果 实验组血清中的6项肿瘤标记物含量均高于对照组;肿瘤标记物水平还与病理类型有关,CEA、CA15-3、CA242以肺腺癌中最高,NSE以肺小细胞癌中最高,CYFRA21-1、TPA以肺鳞癌中最高;血清肿瘤标记物联合检测上述三种肺癌的阳性率显著升高,分别达到100%、96.0%、97.8%.结论 6种肿瘤标记物对于肺癌的诊断有临床价值,并便于确定病理类型,且联合检测可以提高肺癌诊断的敏感性,大大提高肺癌的检出率.     

血清及支气管肺泡灌洗与肺癌标记物

本文就血清及支气管肺泡灌洗液(BAL)中肺癌标记物的研究进展作了简要综述。对常用的几种血清标记物(癌胚抗原、β_2微球蛋白、C反应蛋白、降钙素等)的正常值、阳性检出率以及有关临床应用价值作了说明。并介绍了通过检测BAL中的肺癌标记物(癌胚抗原、降钙素、IgA、IgG等)对肺癌进行早期诊断。     

肺癌的酶类及激素类血清标记物研究现状

<正>肿瘤标记物(Tumor markers,TMs)是肿瘤细胞分泌的物质.通常是肽类.因为正常细胞不分泌或仅少量分泌这些物质,所以正常情况下血清中不存在或仅以低浓度存在TMs.TMs的临床价值在于(1)有助于肿瘤的早期诊断;(2)为预后评价提供指导;(3)有助于选择辅助化疗及有助于评价治疗反应及诊断早期复发.目前研究较多的TMS包括四大类:肿瘤相关抗原、其它多肽类抗原、酶类及激素类.本文就常见的酶类及激素类TMs的研究现状作一简要综述.     

有机性挥发物在肺癌组织和癌细胞株中的检测和分析

目的:通过检测肺癌组织与肺癌细胞株代谢过程中产生的挥发性有机化合物(volatile organic compounds,VOCs),寻找肺癌特征性的气体标记物,为呼吸气体检测在肺癌早期诊断中的应用提供实验依据.方法:利用固相微萃取联合气相色谱质谱联用技术(solid-phase microextraction and gas chromatography-mass spectroscopy,SPME-GCMS)检测18例原发性肺癌患者的手术标本及A549、NCI-H446、SK-MES-1、BEAS-2B 4种细胞株培养液顶空气体中的VOCs,从中筛选与肺癌相关的特征性VOCs组分.结果:2-十五烷酮和十九烷在肺癌细胞株A549、NCI-H446、SK-MES-1中均有表达,2-十五烷酮的表达量分别为(1.382±0.171 )×10-5 mg/L、(1.681±0.190)×10-4 mg/L和(2.835±0.401)×10-6 mg/L;十九烷的表达量分别为(8.382±0.606 )×10-6 mg/L、(1.845±0.130)×10-5 mg/L和(6.220±0.362)×10-6 mg/L;二十烷在肺癌细胞株A549和NCI-H446中有表达,表达量分别为(8.313±1.130)×10-6 mg/L、(1.020±0.141)×10-5 mg/L;而此3种VOCs在对照组BEAS-2B中无表达.在18例肺癌组织中,癸烷、2-十五烷酮、十九烷、二十烷等12种VOCs高表达,其中2-十五烷酮的表达量为5.421×10-6 mg/L～3.621×10-5 mg/L,十九烷为5.805×10-6 mg/L～1.830×10-5 mg/L,二十烷为2.730×10-6 mg/L～2.343×10-5 mg/L;其表达水平与肿瘤分化程度无关(P>0.05).二十烷在非鳞癌中的表达高于鳞癌,此结果与肺癌细胞株的表达情况相符.结论:2-十五烷酮、十九烷、二十烷、癸烷等12种VOCs在肺癌组织中高表达,其中2-十五烷酮、十九烷、二十烷与肺癌细胞株结果相符,提示上述物质可能为肺癌潜在的特征性标志物.     

MicroRNA与非小细胞肺癌

肺癌已经成为全球范围内因癌症导致死亡的首要原因,当今由于缺乏有效的指导临床诊断和治疗的肿瘤分子标志物,所以非小细胞肺癌患者的疗效不佳。Micro RNA(以下简称miRNA)是真核生物中一类长度约为22个核苷酸的参与基因转录后水平调控的小分子非编码RNA。miRNA在肺癌中发挥原癌基因及抑癌基因的作用,在肺癌的发生、发展过程中均发挥着重要作用。miRNA不仅可以在石蜡包埋组织和体液中保持稳定,而且在血清和血浆中也可以稳定存在,这个特性使循环miRNA有望成为一种新型分子标志物,为肺癌的早期分子诊断、预测预后及治疗效果开辟了一个新的研究领域。     

Dietary phytoestrogens and lung cancer risk

Context  Despite lung-specific in vitro and in vivo studies that support a chemopreventive role for phytoestrogens, there has been little epidemiologic research focused on dietary intake of phytoestrogens and risk of lung cancer. Objective  To examine the relationship between dietary intake of phytoestrogens and risk of lung cancer. Design, Setting, and Participants  Ongoing US case-control study of 1674 patients with lung cancer (cases) and 1735 matched healthy controls. From July 1995 through October 2003, participants were personally interviewed with epidemiologic and food frequency questionnaires to collect demographic information and to quantify dietary intake of 12 individual phytoestrogens. Main Outcome Measure  Risk of lung cancer, estimated using unconditional multivariable logistic regression analyses stratified by sex and smoking status and adjusted for established and putative lung cancer risk factors. Results  Reductions in risk of lung cancer tended to increase with each increasing quartile of phytoestrogen intake. The highest quartiles of total phytosterols, isoflavones, lignans, and phytoestrogens were each associated with reductions in risk of lung cancer ranging from 21% for phytosterols (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.64-0.97; P = .03 for trend) to 46% for total phytoestrogens from food sources only (OR, 0.54; 95% CI, 0.42-0.70; P<.001 for trend). Sex-specific effects were also apparent. For men, statistically significant trends for decreasing risk with increasing intake were noted for each phytoestrogen group, with protective effects for the highest quartile of intake ranging from 24% for phytosterols (OR, 0.76; 95% CI, 0.56-1.02; P = .04 for trend) to 44% for isoflavones (OR, 0.56; 95% CI, 0.41-0.76; P<.001 for trend), while in women, significant trends were only present for intake of total phytoestrogens from food sources only, with a 34% (OR, 0.66; 95% CI, 0.46-0.96; P = .01 for trend) protective effect for the highest quartile of intake. The apparent benefits of high phytoestrogen intake were evident in both never and current smokers but less apparent in former smokers. In women, statistically significant joint effects were evident between hormone therapy use and phytoestrogen intake. Specifically, high intake of the lignans enterolactone and enterodiol and use of hormone therapy were associated with a 50% (OR, 0.50; 95% CI, 0.31-0.68; P = .04 for interaction) reduction in risk of lung cancer. Conclusions  While there are limitations and concerns regarding case-control studies of diet and cancer, these data provide further support for the limited but growing epidemiologic evidence that phytoestrogens are associated with a decrease in risk of lung cancer. Confirmation of these findings is still required in large-scale, hypothesis-driven, prospective studies.      

Risk of lung cancer among white and black relatives of individuals with early-onset lung cancer

Context  Evidence exists that lung cancer aggregates in families and recent findings of a chromosomal region linked to lung cancer susceptibility support a genetic component to risk. Family studies of early-onset lung cancer patients offer a unique opportunity to evaluate lifetime risk of lung cancer in relatives. Objective  To measure lung cancer aggregation and estimate lifetime risk among relatives of early-onset cases and population-based controls. Design and Setting  Familial aggregation and cumulative risk estimates from interview data of incident cases and concurrently ascertained controls between 1990 and 2003 in metropolitan Detroit, Mich. Participants  The study included 7576 biological mothers, fathers, and siblings of 692 early-onset cases and 773 frequency-matched controls. One third of the population was black. Main Outcome Measures  Cumulative lifetime risk of lung cancer, stratified by race and smoking behavior in relatives of early-onset cases and controls. Results  Smokers with a family history of early-onset lung cancer in a first-degree relative had a higher risk of developing lung cancer with increasing age than smokers without a family history. An increase in risk occurs after age 60 years in these individuals, with 17.1% (SE 2.4%) of white case relatives and 25.1% (SE 5.8%) of black case relatives diagnosed with lung cancer by age 70 years. Relatives of black cases were at statistically significant increased risk of lung cancer compared with relatives of white cases (odds ratio, 2.07, 95% confidence interval, 1.29-3.32) after adjusting for age, sex, pack-years, pneumonia, and chronic obstructive lung disease. Conclusions  First-degree relatives of black individuals with early-onset lung cancer have greater risk of lung cancer than their white counterparts, and these risks are further amplified by cigarette smoking. These data provide estimates of lung cancer risk that can be used to offer counseling to family members of patients with early-onset lung cancer.      

1635例肺癌术后患者电话随访结果及预后分析

目的:分析肺癌患者术后的电话随访结果及影响肺癌预后的因素,探讨提高电话随访成功率的方法。方法:2011年11月至2012年1月对2002年1月至2011年8月期间1635例本院肺癌手术患者进行电话随访。随访结果及临床资料汇总后进行统计分析,在其中116例临床资料完整的病例中,进一步探讨肺癌转移和长期生存率的影响因素。结果:平均随访成功率为36.1%,电话随访成功率与术后随访间隔时间相关,随访时间与手术间隔时间越近,随访成功率越高。女性患者随访成功率要明显高于男性患者(P<0.001)。40岁以下患者的随访成功率(56%)明显高于50~59岁及60岁以上患者(分别为39%和24%,P<0.001),城镇和农村的随访成功率差异无明显统计学意义(P=0.844)。在116例临床资料完整的病例中,统计验证了转移和高淋巴结分期增加术后死亡的风险(OR值分别为0.212和1.818),腺癌、淋巴结高分期、高龄与术后肿瘤转移相关(OR值分别为2.353,2.181和2.908)。结论:电话随访成功率受时间、年龄及性别等因素影响。在小样本的病例分析中验证了远处转移、淋巴结转移、病理类型及高龄与肺癌预后的关系。