Tumor Biol. (2014) 35:5281–5286 DOI 10.1007/s13277-014-1687-5
RESEARCH ARTICLE
Serum carbohydrate antigen 242 expression exerts crucial function in the diagnosis of pancreatic cancer Xueyan Li & Xiaozhong Guo & Hongyu Li & Hao Lin & Yingwei Sun
Received: 19 December 2013 / Accepted: 22 January 2014 / Published online: 9 February 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
Abstract Pancreatic cancer has the worst prognosis of any gastrointestinal cancer, with the mortality approaching the incidence. Early detection is crucial for improving patients’ prognosis. CA242 has been widely reported to play a role in diagnosis of pancreatic cancer. However, published data on this subject are inconclusive. Therefore, we performed a metaanalysis to evaluate the diagnostic value of CA242 in pancreatic cancer. We searched all the eligible studies through PubMed, Embase, and the Cochrane Library databases without language limitation. Studies were assessed for quality using the quality assessment of studies of diagnostic accuracy (QUADAS). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (SROC). The PLR and NLR and their 95 % confidence interval (CI) were calculated using a fixed effects model according to the Mantel-Haensed method and random effects model based on the work of DerSimonian and Laird, respectively. A total of eight studies were included for analysis. The pooled sensitivity was 0.719 (95 % CI 0.690–0.746). The pooled specificity was 0.868 (95 % CI 0.849–0.885). The DOR estimate was performed and the result was (16.261). Our meta-analysis showed that CA242 could play an important role in the diagnosis of pancreatic cancer.
Keywords Pancreatic cancer . CA242 . Diagnosis . Meta-analysis X. Li (*) : X. Guo : H. Li : H. Lin : Y. Sun Department of Gastroenterology, General Hospital of Shenyang Military Region, Shenyang 110016, China e-mail: [email protected]
Introduction Pancreatic cancer is one of the four or five commonest causes of cancer mortality in developed countries [1]. Approximately 250,000 people are diagnosed with the disease worldwide each year and about the same number die from it. These statistics have not significantly changed over the past several decades [2]. One of the causes is that most patients present with metastatic or locally advanced disease at the time of diagnosis. Given the insidious onset of the malignancy and its extreme resistance to chemo- and radiotherapy, an abundance of research in recent years has focused on identifying biomarkers for the early detection of pancreatic cancer [3]. Despite this, no specific tumor marker for the diagnosis of pancreatic cancer exists. Therefore, pancreatic cancer still represents a major challenge for both research studies and clinical management [4]. CA242 was first isolated in 1985 by Lindholm et al. [5]. It was obtained by immunization of mice with the human adenocarcinoma cell line COLO 205 and fusion with the Sp 2/0 mouse myeloma cell line. The epitope, recognized by the same macromolecule as CA50 and is completely different from the latter, is an isolated carbohydrate structure, whose diagnostic performance is generally thought to be inferior to that of CA19-9 and CA50, but it is also an important serum tumor marker for the diagnosis of pancreatic cancer [6]. Up to now, no meta-analysis was performed for evaluating the diagnostic value of CA242 in pancreatic cancer. We firstly performed this meta-analysis to evaluate the sensitivity and specificity of CA242 in pancreatic cancer and to construct a summary receiver-operating characteristic (SROC) curve, in order to get a more precise result.
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Tumor Biol. (2014) 35:5281–5286
Table 1 Summary of the studies included in the meta-analysis Author
Year
Country
PC
Control
TP
FP
FN
TN
Se
Sp
QUADAS
Rothlin MA Haglund C Banfi G Ozkan H Jiang JT Jiang XT Ni XG Liao Q
1993 1994 1996 2003 2004 2004 2005 2007
Switzerland Finland Italy Turkey China China China China
68 179 42 40 129 96 105 112
262 112 21 95 183 252 100 38
45 132 31 30 105 79 63 57
26 10 3 14 40 16 24 10
23 47 11 10 24 17 42 55
236 102 18 81 143 236 76 28
66.3 74 73.8 75 81.7 82.3 60 59.42
90 91 85 85.5 78.4 93.5 76 72.72
11 12 11 11 10 11 9 12
PC pancreatic cancer, TP true positive, FP false positive, FN false negative, TN true negative, Se sensitivity, Sp specificity
Methods
Inclusion and exclusion criteria of selected studies
Literature search
Articles included in our present work had to meet the following criteria: (a) studies that assessed the diagnostic accuracy of CA242 on pancreatic cancer; (b) the sensitivity and specificity of CA242 P for the diagnosis of pancreatic carcinoma was provided; (c) have presented sufficient data to allow us to calculate the true positive (TP), false negative (FN), false positive (FP), and true negative (TN) values for pancreatic carcinoma diagnosis. When data or subsets of data were presented in more than one article, the article with the most detailed data, or else the article that was most recently published, was chosen. The authors of abstracts and studies that did not report sufficient data were contacted so that we could request additional information. The exclusion criteria were as follows: (a) articles that did not include raw data such as reviews, case reports, comments, editorials, and letters; (b) diagnosis with another existing disease that could not be differentiated from pancreatic cancer. The full text versions of these articles were then read to determine whether they were eligible for inclusion in our study.
A systematic literature search was performed through PubMed, Embase, and the Cochrane Library databases to identify articles on the diagnostic value of CA242 for the detection of pancreatic cancer. All these eligible studies were published until October 21, 2013. The following keywords were used: “CA242 or carbohydrate antigen 242”; “pancreatic carcinoma, pancreatic cancer, carcinoma of pancreas, or pancreatic tumor”; and “sensitivity or specificity, false negative or false positive, diagnosis, detection, or accuracy.” Review articles, letters, editorial comments, case reports, and articles that did not include raw data were discarded. The list of articles was supplemented via extensive cross-checking of the reference lists. There was no limitation on language as well as the sample size of every single study. When there were multiple articles by the same group based on similar patients and using same detection methods, only the largest or the most recent article was included.
Fig. 1 Forest plot of sensitivity of CA242 for the diagnosis of pancreatic cancer
Tumor Biol. (2014) 35:5281–5286
5283
Fig. 2 Forest plot of specificity of CA242 for the diagnosis of pancreatic cancer
Data extraction and assessment of study quality Two investigators independently extracted relevant data on the design and results of each study using a standardized form. Another reviewer assessed all discrepancies, and the majority opinion was used to resolve disagreements between the reviewers. We extracted data from selected articles, which included first authors, years of publication, study population, region, diagnostic cutoff point and time, and methods quality. We created 2×2 tables including the numbers of TP, TN, FP, and FN results in the detection of pancreatic cancer. The sensitivity, specificity, diagnostic odds ratio (DOR), and SROC were the outcome measures used to evaluate diagnostic accuracy. Quality assessment of studies was performed based on the quality assessment of diagnostic accuracy studies (QUADAS) tool [7].
negative test result [8]. Heterogeneity among included studies is assessed by using the Cochrane Q statistic and quantified with the I2 lying between 0 and 100 % [9]. In general, I2 (>50 %) shows that heterogeneity among studies produce some impact, whereas I2 (
RESEARCH ARTICLE
Serum carbohydrate antigen 242 expression exerts crucial function in the diagnosis of pancreatic cancer Xueyan Li & Xiaozhong Guo & Hongyu Li & Hao Lin & Yingwei Sun
Received: 19 December 2013 / Accepted: 22 January 2014 / Published online: 9 February 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
Abstract Pancreatic cancer has the worst prognosis of any gastrointestinal cancer, with the mortality approaching the incidence. Early detection is crucial for improving patients’ prognosis. CA242 has been widely reported to play a role in diagnosis of pancreatic cancer. However, published data on this subject are inconclusive. Therefore, we performed a metaanalysis to evaluate the diagnostic value of CA242 in pancreatic cancer. We searched all the eligible studies through PubMed, Embase, and the Cochrane Library databases without language limitation. Studies were assessed for quality using the quality assessment of studies of diagnostic accuracy (QUADAS). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (SROC). The PLR and NLR and their 95 % confidence interval (CI) were calculated using a fixed effects model according to the Mantel-Haensed method and random effects model based on the work of DerSimonian and Laird, respectively. A total of eight studies were included for analysis. The pooled sensitivity was 0.719 (95 % CI 0.690–0.746). The pooled specificity was 0.868 (95 % CI 0.849–0.885). The DOR estimate was performed and the result was (16.261). Our meta-analysis showed that CA242 could play an important role in the diagnosis of pancreatic cancer.
Keywords Pancreatic cancer . CA242 . Diagnosis . Meta-analysis X. Li (*) : X. Guo : H. Li : H. Lin : Y. Sun Department of Gastroenterology, General Hospital of Shenyang Military Region, Shenyang 110016, China e-mail: [email protected]
Introduction Pancreatic cancer is one of the four or five commonest causes of cancer mortality in developed countries [1]. Approximately 250,000 people are diagnosed with the disease worldwide each year and about the same number die from it. These statistics have not significantly changed over the past several decades [2]. One of the causes is that most patients present with metastatic or locally advanced disease at the time of diagnosis. Given the insidious onset of the malignancy and its extreme resistance to chemo- and radiotherapy, an abundance of research in recent years has focused on identifying biomarkers for the early detection of pancreatic cancer [3]. Despite this, no specific tumor marker for the diagnosis of pancreatic cancer exists. Therefore, pancreatic cancer still represents a major challenge for both research studies and clinical management [4]. CA242 was first isolated in 1985 by Lindholm et al. [5]. It was obtained by immunization of mice with the human adenocarcinoma cell line COLO 205 and fusion with the Sp 2/0 mouse myeloma cell line. The epitope, recognized by the same macromolecule as CA50 and is completely different from the latter, is an isolated carbohydrate structure, whose diagnostic performance is generally thought to be inferior to that of CA19-9 and CA50, but it is also an important serum tumor marker for the diagnosis of pancreatic cancer [6]. Up to now, no meta-analysis was performed for evaluating the diagnostic value of CA242 in pancreatic cancer. We firstly performed this meta-analysis to evaluate the sensitivity and specificity of CA242 in pancreatic cancer and to construct a summary receiver-operating characteristic (SROC) curve, in order to get a more precise result.
5282
Tumor Biol. (2014) 35:5281–5286
Table 1 Summary of the studies included in the meta-analysis Author
Year
Country
PC
Control
TP
FP
FN
TN
Se
Sp
QUADAS
Rothlin MA Haglund C Banfi G Ozkan H Jiang JT Jiang XT Ni XG Liao Q
1993 1994 1996 2003 2004 2004 2005 2007
Switzerland Finland Italy Turkey China China China China
68 179 42 40 129 96 105 112
262 112 21 95 183 252 100 38
45 132 31 30 105 79 63 57
26 10 3 14 40 16 24 10
23 47 11 10 24 17 42 55
236 102 18 81 143 236 76 28
66.3 74 73.8 75 81.7 82.3 60 59.42
90 91 85 85.5 78.4 93.5 76 72.72
11 12 11 11 10 11 9 12
PC pancreatic cancer, TP true positive, FP false positive, FN false negative, TN true negative, Se sensitivity, Sp specificity
Methods
Inclusion and exclusion criteria of selected studies
Literature search
Articles included in our present work had to meet the following criteria: (a) studies that assessed the diagnostic accuracy of CA242 on pancreatic cancer; (b) the sensitivity and specificity of CA242 P for the diagnosis of pancreatic carcinoma was provided; (c) have presented sufficient data to allow us to calculate the true positive (TP), false negative (FN), false positive (FP), and true negative (TN) values for pancreatic carcinoma diagnosis. When data or subsets of data were presented in more than one article, the article with the most detailed data, or else the article that was most recently published, was chosen. The authors of abstracts and studies that did not report sufficient data were contacted so that we could request additional information. The exclusion criteria were as follows: (a) articles that did not include raw data such as reviews, case reports, comments, editorials, and letters; (b) diagnosis with another existing disease that could not be differentiated from pancreatic cancer. The full text versions of these articles were then read to determine whether they were eligible for inclusion in our study.
A systematic literature search was performed through PubMed, Embase, and the Cochrane Library databases to identify articles on the diagnostic value of CA242 for the detection of pancreatic cancer. All these eligible studies were published until October 21, 2013. The following keywords were used: “CA242 or carbohydrate antigen 242”; “pancreatic carcinoma, pancreatic cancer, carcinoma of pancreas, or pancreatic tumor”; and “sensitivity or specificity, false negative or false positive, diagnosis, detection, or accuracy.” Review articles, letters, editorial comments, case reports, and articles that did not include raw data were discarded. The list of articles was supplemented via extensive cross-checking of the reference lists. There was no limitation on language as well as the sample size of every single study. When there were multiple articles by the same group based on similar patients and using same detection methods, only the largest or the most recent article was included.
Fig. 1 Forest plot of sensitivity of CA242 for the diagnosis of pancreatic cancer
Tumor Biol. (2014) 35:5281–5286
5283
Fig. 2 Forest plot of specificity of CA242 for the diagnosis of pancreatic cancer
Data extraction and assessment of study quality Two investigators independently extracted relevant data on the design and results of each study using a standardized form. Another reviewer assessed all discrepancies, and the majority opinion was used to resolve disagreements between the reviewers. We extracted data from selected articles, which included first authors, years of publication, study population, region, diagnostic cutoff point and time, and methods quality. We created 2×2 tables including the numbers of TP, TN, FP, and FN results in the detection of pancreatic cancer. The sensitivity, specificity, diagnostic odds ratio (DOR), and SROC were the outcome measures used to evaluate diagnostic accuracy. Quality assessment of studies was performed based on the quality assessment of diagnostic accuracy studies (QUADAS) tool [7].
negative test result [8]. Heterogeneity among included studies is assessed by using the Cochrane Q statistic and quantified with the I2 lying between 0 and 100 % [9]. In general, I2 (>50 %) shows that heterogeneity among studies produce some impact, whereas I2 (
