肿瘤标志物M2-PK的生物学特性和临床应用

在实体肿瘤诊治过程中，肿瘤标志物的监测对于肿瘤的诊断、分型和监测治疗效果及判断预后有极其重要的临床价值。近年来肿瘤标志物M2-PK与肿瘤的关系成为研究的热点，其血清表达水平与乳腺癌、肺癌、胃肠道肿瘤、肾细胞癌和胰腺癌的病理生理学发展过程密切相关，现对这一领域的研究进展作一综述。     

肿瘤型M2 丙酮酸激酶的生物学特性及临床应用

 肿瘤型M2丙酮酸激酶（TUM2-PK）是近年来研究较多的一种新型肿瘤标志物，在恶性肿瘤的早期诊断中显示较好的应用前景。本文主要就肿瘤型M2-PK的生物学特性及临床应用作一综述。     

多种肿瘤标志物在检验乳腺癌的临床应用

目的 探讨12项肿瘤标志物指标在乳腺癌中的表达及临床意义.方法 采用蛋白芯片法榆测术前乳腺癌(74例)及正常对照组(158例)中的12项肿瘤标志物.结果 12项指标,乳腺癌组较正常埘照组高,差异具有统计学意义的指标有:CA125、CA153、CEA、CA199、Ferrtin,但敏感性及特异性均不高.结论 单项指标诊断乳腺癌的准确性均不高,CA125、CA153、CEA、CA199联检是诊断乳腺癌较好方法.     

乳腺肿瘤标志物的研究进展

乳腺肿瘤标志物的检测与红外线扫描、数字X线、超声及磁共振成像扫描等影像学检查相结合提高了乳腺癌的诊断效率。预测预后的肿瘤标志物在个体化治疗和鉴别复发、转移的危险性方面有重要作用。到目前为止已有很多关于乳腺肿瘤标志物方面的研究。通过对总生存时间、无病生存时间、生活质量、毒性及费用一效益等方面的比较，有些乳腺肿瘤标志物的临床应用已被更新。     

乳腺恶性肿瘤标志物检测的临床应用

目的：探讨肿瘤标志物在乳腺恶性肿瘤诊断和 治疗监测方面的临床应用价值。方法：对81例乳腺恶性肿瘤，17例乳腺良性肿瘤，39例健康成年人进行血清CA15-3，CA19-9，CA24-2，CA125和CEA5项指标的监测，并进行对比分析。结果：把CA19-9和CA24-2组合起来进行检测。阳性率可达80.2%，手术和化疗均可使肿瘤标志物的水平下降。结论：肿瘤标志物不同方式的联合检测对乳腺恶性肿瘤的诊断和治疗的监测具有临床应用价值。     

乳腺癌外周血肿瘤标志物及其在随访中的应用

尽管乳腺癌总体生存时间较长,但复发和转移仍是其治疗失败的主要原因,临床上急需寻找一种简单易行的肿瘤复发监测方法。随着人们对乳腺癌认识的深入和实验室技术的不断提高,肿瘤标志物在乳腺癌早期诊断、预后预测和复发监测等方面的作用越来越受到重视,也为乳腺癌研究开辟了新的领域。     

肿瘤M2型丙酮酸激酶检测在胆管癌诊断中的临床价值

目的: 探讨肿瘤M2型丙酮酸激酶(TumorM2-PK,TuM2-PK)检测对胆管癌的临床诊断及临床分期的应用价值。 方法: 选取天津医科大学附属肿瘤医院2005年1月至2007年12月间120例胆管癌患者及同期170例对照者(120例健康体检者,50例良性病变者),应用酶结合免疫吸附测定(ELISA)法分别检测血浆中TuM2-PK和血清中糖类抗原19-9(CA19-9)的水平。采用的正常参考值分别为TuM2-PK<18U/ml,CA19-9<37U/ml。 结果: 胆管癌患者血浆中TuM2-PK和CA19-9水平明显高于对照组(P<0.05)。在胆管癌的诊断中单独检测时TuM2-PK、CA19-9敏感性分别为85%、67%,特异性分别为88%、72%,联合测定敏感性、特异性分别达到95%、96%。不同部位和不同病理类型胆管癌血浆中TuM2-PK水平差异无统计学意义(P>0.05),而Ⅰ+Ⅱ期和Ⅲ+ⅣA+ⅣB期之间差异有统计学意义(P<0.05),并且TuM2-PK对Ⅲ+ⅣA+ⅣB期胆管癌诊断的敏感性较Ⅰ+Ⅱ期胆管癌升高(P<0.05)。 结论: TuM2-PK对于胆管癌的诊断有重要的临床意义,且联合CA19-9可明显提高诊断胆管癌的敏感性和特异性,TuM2-PK水平可能作为胆管癌术前临床分期的一个判断指标。     

12项肿瘤标志物检测乳腺癌的临床意义

[目的]了解12项肿瘤标志物指标在乳腺癌中的表达.[方法]采用蛋白芯片法检测术前乳腺癌75例及正常对照组160例12项肿瘤标志物.[结果]12项指标中乳腺癌组较正常对照组高,且具有统计学意义的指标有:CA125、CA153、CEA、CA199、Ferritin;但敏感性及特异性均不高.[结论]单项指标诊断乳腺癌的准确性均不高,价值有限,CA125、CA153、CEA、CA199是联合诊断乳腺癌可选指标.     

消化道肿瘤标志物研究进展及临床应用

消化道肿瘤是发病率和死亡率最高的肿瘤之一。为了提高消化道肿瘤的临床筛选和诊断水平,近年来各国对消化道肿瘤标志物的发掘和临床应用方面做了大量研究。肿瘤标志物特异性、敏感性不断提高,假阳性逐渐降低,对肿瘤早期发现、区别良恶性肿瘤及病变范围、监测治疗效果及肿瘤复发、预后均有作用。新的肿瘤标志物不断问世,本文对消化道肿瘤标志物研究进展及临床应用价值予以简要介绍。     

The pyruvate kinase isoenzyme M2 (Tu M2-PK) as a tumour marker for renal cell carcinoma

The M2 isoenzyme of pyruvate kinase (M2-PK) is specially expressed by tumour cells (Tu M2-PK) and has been detected in the peripheral blood of patients with renal cell carcinoma (RCC). We analysed the benefit of using Tu M2-PK as a tumour marker for primary detection of RCC by receiver operating characteristic (ROC) analysis. The area under the curve was 0.674, and the sensitivity, specificity and positive predictive value (PPV) were 44.4%, 87.5% and 88%, respectively, at the ROC optimal cut-off of 28.2 kU/L. We examined 71 patients. Since the marker sensitivity for detection of the early stages T1 and T2 was only 47% it is not suggested to use this marker for primary diagnosis of RCC. Its use as part of the confirmatory preoperative evaluation might be considered in view of its high PPV.     

Tumour M2-PK as a stool marker for colorectal cancer: comparative analysis in a large sample of unselected older adults vs colorectal cancer patients

Stool testing based on tumour-derived markers might offer a promising approach for non-invasive colorectal cancer (CRC) screening. The aim of this study was to estimate the potential of a new test for faecal tumour M2-PK to discriminate patients with CRC from a large sample of unselected older adults. Faecal tumour M2-PK concentrations were determined in 65 CRC patients and in a population-based sample of 917 older adults (median age: 65 and 62 years, respectively). Sensitivity and specificity of the test were calculated at different cutoff values, and receiver-operating characteristic curves (ROC) were constructed to visualise the discriminatory power of the test. The median (interquartile range) faecal tumour M2-PK concentration was 8.6 U ml(-1) (2.8-18.0) among CRC patients and <2 U ml(-1) (<2-3.2; P<0.0001) in the population sample. At a cutoff value of 4 U ml(-1), sensitivity (95% confidence interval) was 85% (65-96%) for colon cancer and 56% (41-74%) for rectum cancer. Specificity (95% confidence interval) was estimated to be 79% (76-81%). Given the comparatively high sensitivity of the tumour M2-PK stool test (especially for colon cancer) and its simple analysis, the potential use of the test for early detection of CRC merits further investigation. Possibilities to enhance specificity of the test should be explored.     

Tumor type M2 pyruvate kinase (TuM2-PK) as a novel plasma tumor marker in melanoma

Proliferating cells express the pyruvate kinase isoenzyme type M2 (M2-PK). This enzyme exists as an active tetramer and an inactive dimer. The dimeric form is predominantly found in tumor cells and is therefore termed Tumor M2-PK (TuM2-PK). TuM2-PK molecules are released into the peripheral blood and may hereby function as a marker of tumor load in cancer patients. Our study was aimed to investigate TuM2-PK as a potential plasma marker in melanoma patients compared to the well-established serum marker S100beta. We measured the concentration of TuM2-PK in plasma and S100beta in corresponding serum samples from 300 melanoma patients and 53 healthy controls using a sandwich ELISA and an immunoluminometric assay, respectively. Plasma concentrations of TuM2-PK were significantly increased in melanoma patients compared to healthy controls (9.30 U/ml vs. 7.20 U/ml; p = 0.0036) and correlated with tumor load (p < 0.0005) and disease stage (p < 0.0005). Patients with elevated plasma TuM2-PK (cut-off = 15 U/ml) presented a reduced overall (p < 0.000005) and progression-free (p = 0.023) survival. Multivariate analysis revealed plasma TuM2-PK and serum S100beta as independent predictors of overall survival in metastasized patients. Neither plasma TuM2-PK nor serum S100beta showed prognostic relevance for tumor-free patients. Although the sensitivity and specificity to predict disease progression or death was higher for serum S100beta compared to plasma TuM2-PK, the combination of both markers improved the estimation of prognosis compared to that of serum S100beta alone.     

Prospective multicenter evaluation of fecal tumor pyruvate kinase type M2 (M2-PK) as a screening biomarker for colorectal neoplasia

Proliferating cells, particularly the tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed M2-PK. It's a direct target of several oncoproteins; the determination of fecal tumor pyruvate kinase type M2 (M2-PK) might be another promising tool for colorectal cancer (CRC) screening. In this study, we have evaluated fecal M2-PK as a screening biomarker for colorectal neoplasia. It was compared against fecal occult blood (FOB) and colonoscopy. Three hundred and seventeen consecutive subjects from 4 different centers were included. Stool specimens were collected before purgation, processed appropriately and were tested for FOB and quantitatively analyzed for M2-PK. Colonoscopies were performed by experienced endoscopists who were unaware of fecal assay results. At cutoff value of 4 U/ml, fecal M2-PK assay had a sensitivity, specificity, PPV and NPV of 81.1, 86.7, 71.1 and 61.9% respectively for diagnosing CRC whereas FOBT showed a sensitivity of 36.5%, specificity of 92.2%, PPV of 72.9% and NPV of 71.5% for CRC. Such low specificity of fecal M2-PK will lead to unacceptably high number of false positives if it is used for mass CRC screening, leading to unindicated colonoscopies with its associated inconveniences, risks and costs. CRC screening test must have high specificity; a high sensitivity is not as vital. To conclude, M2-PK was found to be a poor screening biomarker for CR neoplasia in a subject population at above average risk based on its prospective comparison with colonoscopy. These marginal performance characteristics do not permit its use as a screening tool for CR neoplasia in present clinical settings.     

肿瘤M2型丙酮酸激酶在恶性胸腔积液中的诊断价值

目的 探讨肿瘤M2型丙酮酸激酶(Tu M2-PK)对鉴别结核性与肺癌性胸腔积液的临床价值.方法 50例恶性、48例结核性胸腔积液患者,采用酶联免疫吸附法(ELISA)测定血清和胸腔积液中的Tu M2-PK和CEA的水平.结果 肺癌性胸腔积液患者血清和胸腔积液中Tu M2-PK,CEA的表达水平与结核性胸腔积液患者比较有...     

血浆肿瘤型M2丙酮酸激酶检测在直肠癌诊断中的价值

目的:探讨血浆肿瘤型M2丙酮酸激酶（TUM2-PK）检测在直肠癌诊断中的价值。方法:直肠癌患者68例,同时纳入健康者82例作为研究的对照组。采用酶联免疫吸附试剂（ELISA）法检查血浆TUM2-PK水平,分析血浆TUM2-PK与直肠癌分期、淋巴结转移、性别、年龄的相关性以及对直肠癌临床诊断的灵敏度、特异度以及阳性预测值等。另外,对患者血癌胚抗原（CEA）表达水平进行检测,并对其与TUM2-PK水平进行比较,绘制ROC曲线分析其作为直肠癌诊断指标的临床价值。结果:直肠癌组与对照组血浆TUM2-PK、CEA水平分别为（29.71±13.43）U/ml、（13.45±2.02）ng/ml,对照组分别为（8.69±2.62）U/ml、（2.10±0.75）ng/ml,组间差异均有显著性（P<0.05）。血浆TUM2-PK阳性表达率与患者的病理分级以及淋巴结转移相关,差异有显著性（P<0.05）。血浆TUM2-PK诊断直肠癌的灵敏度、特异度、阳性预测值分别为64.71%、76.83%、69.84%。血浆CEA诊断直肠癌的灵敏度、特异度、阳性预测值分别为47.06%、64.63%、52.46%。两者联合诊断直肠癌的灵敏度、特异度、阳性预测值分别为94.33%、85.61%、91.23%。结论:血浆TUM2-PK检测能够作为临床早期诊断直肠癌,判断临床分析,评估治疗预后的重要指标。其灵敏度与阳性预测值均显著高于CEA,而两者联合检测能够进一步提高直肠癌的临床诊断准确率。     

Faecal tumour M2 pyruvate kinase: a new, sensitive screening tool for colorectal cancer

Proliferating cells, especially tumour cells, express a special isoenzyme of pyruvate kinase, termed M2-PK, which can occur in a tetrameric form with a high affinity to its substrate, phosphoenolpyruvate (PEP), and in a dimeric form with a low PEP affinity. In tumour cells, the dimeric form is usually predominant and is therefore termed Tumour M2-PK. The levels of Tumour M2-PK within tumours and in EDTA-plasma correlate with staging and the ability of the tumour cells to metastasise. Since most colorectal tumours grow intraluminally, it appeared interesting to determine whether Tumour M2-PK is detectable in the faeces of tumour patients. Stool samples were tested by ELISA from controls without colorectal cancer and colorectal cancer patients. Whereas Tumour M2-PK levels were low in the control group (mean value+/-s.e.m.: 3.3+/-0.4, n=144), they were high in the case of colorectal cancer (56.1+/-15.3, n=60). At a cutoff value of 4 U ml(-1), the sensitivity was 73%. TNM and Dukes' classification of the tumours revealed a strong correlation between faecal Tumour M2-PK levels and staging. The determination of Tumour M2-PK in faeces provides a new promising screening tool for colorectal tumours.     

结直肠恶性肿瘤的新标志物-肿瘤型丙酮酸激酶

肿瘤型丙酮酸激酶是近年来发现的一种新型肿瘤标志物,在消化道肿瘤早期诊断、疗效监测等方面的应用价值已得到证实。本文就其在结直肠癌的早期筛查、动态监测等方面的临床应用价值做一综述。     

Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in human biliary tract cancer

BACKGROUND:

The early diagnosis of biliary tract cancer (BTC) remains challenging, and there are few effective therapies. This study investigated whether the M2 isotype of pyruvate kinase (M2‐PK), which serves as the key regulator of cellular energy metabolism in proliferating cells, could play a role in the diagnosis and therapy of BTC.

METHODS:

Plasma and bile M2‐PK concentrations were measured by enzyme‐linked immunosorbent assay in 88 patients with BTC, 79 with benign biliary diseases, and 17 healthy controls. M2‐PK expression was assayed in a BTC tissue array by immunohistochemistry. The role of M2‐PK in tumor growth, invasion, and angiogenesis was evaluated in BTC cell lines by retrovirus‐mediated M2‐PK transfection and short hairpin RNA silencing techniques.

RESULTS:

Sensitivity (90.3%) and specificity (84.3%) of bile M2‐PK for malignancy were significantly higher than those for plasma M2‐PK and serum carbohydrate antigen 19‐9. M2‐PK expression was specific for cancer cells and correlated with microvessel density. M2‐PK positivity was a significant independent prognostic factor by multivariable analysis. Transfection of M2‐PK in a negatively expressed cell line (HuCCT‐1 cells) increased cell invasion, whereas silencing in an M2‐PK–positive cell line (TFK cells) decreased tumor nodule formation and cellular invasion. A significant increase in endothelial tube formation was noted when supernatants from M2‐PK–transfected cells were added to an in vitro angiogenesis assay, whereas supernatants from silenced cells negated endothelial tube formation.

CONCLUSIONS:

Bile M2‐PK is a novel tumor marker for BTC and correlates with tumor aggressiveness and poor outcome. Short hairpin RNA–mediated inhibition of M2‐PK indicates the potential of M2‐PK as a therapeutic target. Cancer 2013. © 2012 American Cancer Society.