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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 5  |  Page : 104-106

Tumor M2 pyruvate kinase in diagnosis of nonsmall cell lung cancer: A meta-analysis based on Chinese population


1 Department of Radiotherapy, Huaihe Hospital of Henan University, Henan, Kaifeng 475000, China
2 Department of Nuclear Medicine, Huaihe Hospital of Henan University, Henan, Kaifeng 475000, China

Date of Web Publication31-Aug-2015

Correspondence Address:
Dapeng Wu
Department of Radiotherapy, Huaihe Hospital of Henan University, Henan, Kaifeng 475000
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.163857

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 > Abstract 

Objective: The purpose of this study was to evaluate the value of tumor M2 pyruvate kinase (tumor M2-PK) in the diagnosis of nonsmall cell lung cancer.
Methods: The diagnosis clinical studies of tumor M2-PK in the diagnosis of nonsmall cell lung cancer were electronic researched in the Medline, EMBASE, WANFANG, and CNIK databases. The data of true positive, false positive, false negative, and true negative were extracted from each of the individual studies. We use  Stata11.0 (http://www.stata.com; Stata Corporation, College Station, TX) and MetaDiSc 1.4 software to pool the diagnostic sensitivity, specificity, and diagnostic area under the receiver operating characteristic (ROC).
Results: Eleven diagnostic clinical studies with 1294 subjects were included in this diagnostic meta-analysis. The combined sensitivity, specificity, positive likely hood ratio, negative likely hood ratio were 0.69 (0.65-0.72), 0.92 (0.89-0.94), 7.84 (5.92-10.38), 0.36 (0.32-0.40). And the area under the ROC curve was 0.92 (0.90-0.94).
Conclusion: Serum tumor M2-PK can be a potential biomarker for diagnosis of nonsmall cell lung cancer.

Keywords: Diagnosis, meta-analysis, nonsmall cell lung cancer, tumor M2 pyruvate kinase


How to cite this article:
Liu J, Zhu H, Jiang H, Zhang H, Wu D, Hu X, Zhang H. Tumor M2 pyruvate kinase in diagnosis of nonsmall cell lung cancer: A meta-analysis based on Chinese population. J Can Res Ther 2015;11:104-6

How to cite this URL:
Liu J, Zhu H, Jiang H, Zhang H, Wu D, Hu X, Zhang H. Tumor M2 pyruvate kinase in diagnosis of nonsmall cell lung cancer: A meta-analysis based on Chinese population. J Can Res Ther [serial online] 2015 [cited 2017 Nov 19];11:104-6. Available from: http://www.cancerjournal.net/text.asp?2015/11/5/104/163857

Juncai Liu and Hongjing Zhu contribute equally to this work.



 > Introduction Top


Pyruvate kinase is important in the glycolytic pathway. The important function of pyruvate kinase is to control nucleotide triphosphate generation. [1],[2] Different isoforms of this enzyme exist (pyruvate kinases L, R, M1, M2, tumor M2), which are tissue-specifically expressed in various organisms. [3] Several studies reported that the tumor M2 pyruvate kinase (tumor M2-PK) can be detected in body fluids, most likely released from tumor cells by tumor necrosis and cell turnover. It can be detected by a sandwich-ELISA based on two monoclonal antibodies. [3] And it is reported that the serum level of tumor M2-PK was always elevated in nonsmall cell lung cancer patients. [4],[5] But whether it can be a biomarker for diagnosis of nonsmall cell lung cancer is not clear. Hence, we performed this meta-analysis by pooling the published data in order to evaluate further the diagnostic value for tumor M2-PK in the diagnosis of nonsmall cell lung cancer.


 > Methods Top


A systematic electronic search of the medical literature was performed in March 2015 to identify the clinical diagnostic studies of tumor M2-PK in the diagnosis of nonsmall cell lung cancer. The databases were restricted to Medlin, PubMed, WANFANG and CNIK. And the manual search of references cited in review papers as well as in all original papers identified by the search was also performed to complete the search. The general information and exact data were extracted from the original studies by two reviews independently. The general information was included first author name, the year of publication, a country the trail was done, cut-off the value of serum tumor M2-PK. The number of true positive, false positive, false negative, and true negative was extracted from each study for pool the diagnosis sensitivity, specificity, positive likely hood ratio, negative likely hood ratio.

Statistical analysis

We use MetaDiSc 1.4 statistical software (http://www.biomedsearch.com/nih/Meta-DiSc-software-meta-analysis/16836745.html) to do the statistical analysis. We first evaluate the statistical heterogeneity among the included studies before pooling the diagnosis specificity, positive likely hood ratio, negative likely hood ratio. If heterogeneity was found across the trials, the pooled results were calculated based on random effect model. Otherwise, the fixed-effect model was used. Heterogeneity was tested using the Z-score andχ2 in which P < 0.1 was considered as statistically significant. [6]


 > Results Top


We finally included 11 papers in this meta-analysis. [4],[5],[7],[8],[9],[10],[11],[12],[13],[14],[15] The publication year range from 2007 to 2011. The tumor M2-PK was tested by ELISA array in all of the included 11 studies. Five studies reported the cut-off value of tumor M2-PK with 15 U/ml, one with cut-off value of 13 U/ml, one with 16.5 U/ml and other 3 not reporting the cut-off value. The main characteristics of the 11 articles are shown in [Table 1].
Table 1: The main characteristics of the 11 articles


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For the diagnostic sensitivity, no statistical heterogeneity was existed across the 11 studies. The data were pooled by fixed effects model. The pooled results demonstrated that the combined sensitivity, specificity, positive likely hood ratio, negative likely hood ratio were 0.69 (0.65-0.72) [Figure 1], 0.92 (0.89-0.94) [Figure 2], 7.84 (5.92-10.38), 0.36 (0.32-0.40). And the area under the receiver operating characteristic (ROC) curve (AUC) was 0.92 (0.90-0.94) [Figure 3]. We evaluate the publication bias by line regression tests. And no significant publication bias was found in this meta-analysis [Figure 4].
Figure 1: Forest plot of sensitivity for diagnosis of lung cancer by tumor M2 pyruvate kinase

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Figure 2: Forest plot of specificity for diagnosis of lung cancer by Tumor M2 pyruvate kinase

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Figure 3: Diagnostic receiver operating characteristic curve for tumor M2 pyruvate kinase

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Figure 4: Funnel plot for evaluation publication bias

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 > Discussion Top


Carcinoma of lung is the first cause of cancer-associated mortality in the United States and worldwide. [16],[17],[18],[19] The prognosis of lung cancer is poor for its late diagnosis. It is reported that the 5-year survival rate was only 15.9% because of most patients had advanced or metastasis stage disease. Hence, the detection of early nonsmall cell lung cancer is very important for improving the prognosis of this disease.

Tumor M2-PK can be detected in body fluids, most likely released from tumor cells by tumor necrosis and cell turnover. It can be detected by a sandwich-ELISA based on two monoclonal antibodies. [3] Several diagnostic studies have evaluated the clinical efficacy of tumor M2-PK as the biomarker for diagnosis of nonsmall cell lung cancer. Lianzhou et al.[4] recruited 90 nonsmall lung cancer patients and 90 benign lung disease in their study. They test the serum level of tumor M2-PK of these patients. The results showed the serum level of tumor-M2-PK in the lung cancer group was much higher than that of the benign lung disease group. And the diagnostic sensitivity and specificity of tumor M2-PK was 68.9% and 91% respectively. [4] Another study evaluates the value of tumor type M2-PK in the diagnosis of lung cancer. In that study, the author includes 92 lung cancer patients and 77 benign lung disease. They use ELISA array tested the serum level of tumor M2-PK and fond the diagnostic sensitivity, the specificity of tumor M2-PK was 71.0% and 96.7%. The diagnostic value of serum tumor M2-PK was not conclusive in the previously published articles. Thus, we perform this meta-analysis in order to make a conclusion. In our meta-analysis, we include eleven diagnostic clinical studies with 1294 subjects. The combined sensitivity, specificity, positive likely hood ratio, negative likely hood ratio were 0.69 (0.65-0.72), 0.92 (0.89-0.94), 7.84 (5.92-10.38), and 0.36 (0.32-0.40). And the AUC was 0.92 (0.90-0.94). These results indicated that serum tumor M2-PK can be a potential biomarker for diagnosis of nonsmall cell lung cancer.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Mazurek S, Grimm H, Boschek CB, Vaupel P, Eigenbrodt E. Pyruvate kinase type M2: A crossroad in the tumor metabolome. Br J Nutr 2002;87 Suppl 1:S23-9.  Back to cited text no. 1
    
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Mazurek S, Zwerschke W, Jansen-Dürr P, Eigenbrodt E. Effects of the human papilloma virus HPV-16 E7 oncoprotein on glycolysis and glutaminolysis: Role of pyruvate kinase type M2 and the glycolytic-enzyme complex. Biochem J 2001;356(Pt 1):247-56.  Back to cited text no. 2
    
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Zhang B, Chen JY, Chen DD, Wang GB, Shen P. Tumor type M2 pyruvate kinase expression in gastric cancer, colorectal cancer and controls. World J Gastroenterol 2004;10:1643-6.  Back to cited text no. 3
    
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Lianzhou C, Wen L, Wentao Z, Qian F, dong W, Qian W. The diagnostic values of the tumor markers for lung cancer. Chin J Exp Surg 2008;25:1128-9.  Back to cited text no. 4
    
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Fang H, Min B, Jianqun X. Diagnostic value of combined detection of tumor M2 pyruvate kinase and carcinoembryonic antigen for lung caner. J Intern Intensive Med 2009;15:249-51.  Back to cited text no. 5
    
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Dong W, Juan Z, Min L, Hongxu X. The value of tumor type M2 pyruvate kinase in the diagnosis of lung cancer. Chin J Lab Med 2007;30:541-3.  Back to cited text no. 7
    
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Xiaoqin L, Hongxia Z, Jing S, Zhixiang D. Diagnostic value of three tumor markers (tumor M2-PK, CEA, CYFRA21-1) as analyzed with application of logistic regression and ROC curve in patients with non-small-cell lung cancer. J Radioimmunology 2008;21:586-8.  Back to cited text no. 8
    
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Jiaqing Z, Man-Man YE, Dong W, Shi-Hong Z. The diagnostic values of tumor type M2 pyruvate kinase combined with other tumor markers for lung cancer. J Pract Med 2008;24:2509-10.  Back to cited text no. 9
    
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Jianping Q, Zhixiang D, Chuxiu Y, Wentao J. Diagnosis value of combined detection of plasma tumor M2-PK and serum NSE levels in patients with small cell lung cancer. J Radioimmunology 2008;21:172-3.  Back to cited text no. 10
    
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Xin Z, c Z. Clinical value of combined detection of TU M2-PK, NSE, CEA and CYFRA21-1 in the diagnosis of lung cancer. Aerosp Med 2009;20:31-3.  Back to cited text no. 11
    
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Yanbin Z, Xiansheng Z, Pin X, Suqiong T, Maohong H. Value of ADAM8 and M2-PK to the diagnosis of non-small cell lung cancer in the early stage. J Chin Pract Diagn Ther 2010;24:116-8.  Back to cited text no. 12
    
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Shangde G, Zhongyi W, Hong L, Yunchun L, Zhang LI. Clinical value of combined determination of TU M2-PK, TPS, CEA in the patients with lung cancer. China Med Her 2011;08:20-2.  Back to cited text no. 13
    
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Weida F, Wenyong L, Qichang X. The clinical significance of tumor type M2 pyruvate kinase level in patients with lung cancer. J Mod Oncol 2011;19:1352-3.  Back to cited text no. 14
    
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Diyi L, Ping C, Ji C, Jiliang Z, Li Z. Tumor type M2 pyruvate kinase in diagnosis of lung cancer. Chin J Respir Crit Care Med 2011;10:494-5.  Back to cited text no. 15
    
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Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 16
    
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Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.  Back to cited text no. 17
    
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Chen W. Cancer statistics: Updated cancer burden in China. Chin J Cancer Res 2015;27:1.  Back to cited text no. 18
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Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]



 

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