|Year : 2014 | Volume
| Issue : 7 | Page : 222-224
A meta-analysis of serum cancer antigen 125 array for diagnosis of ovarian cancer in Chinese
Xiao-Yan Liao1, Guo-Jun Huang2, Chao Gao2, Guang-Hong Wang2
1 Department of Gynaecology and Obstetrics, Chengdu Women's and Children's Central Hospital, Chengdu 610091, China
2 Department of Oncology, The People's Hospital of Pi County, Chengdu, 611730, China
|Date of Web Publication||29-Nov-2014|
Department of Oncology, The People's Hospital of Pi County, Chengdu, 611730
Source of Support: None, Conflict of Interest: None
Objective: To further evaluation the diagnosis accuracy of serum cancer antigen 125 (CA125) in the diagnosis of ovarian cancer in Chinese patients.
Materials and Methods: The PubMed, Wanfang and CNKI databases were electric searched and relevant diagnosis trials were reviewed and finally included in this meta-analysis. The diagnosis sensitivity, specificity, positive likely hood ratio (+LR), negative likely hood ratio (−LR), diagnostic odds ratio (DOR) and receiver operating characteristic curve were pooled by Meta DiSc 1.4 software.
Results: Nineteen studies with a total of 2426 subjects were included in this meta-analysis. The pooled sensitivity, specificity, +LR, −LR and DOR were 0.75 (95% confidence interval = 0.73-0.78), 0.80 (0.77-0.82), 4.52 (3.27-6.26), 0.31 (0.28-0.35) and 15.76 (10.45-23.75) respectively. The area under the summary receiver operating characteristic curve was 0.84.
Conclusion: Serum CA125 was potential biomarker for diagnosis of ovarian cancer with acceptable diagnosis value.
Keywords: Cancer antigen 125, diagnosis, meta-analysis, ovarian cancer
|How to cite this article:|
Liao XY, Huang GJ, Gao C, Wang GH. A meta-analysis of serum cancer antigen 125 array for diagnosis of ovarian cancer in Chinese. J Can Res Ther 2014;10, Suppl S3:222-4
Xiao-Yan Liao and Guo-Jun Huang contribute equally to this work
| > Introduction|| |
Cancer antigen 125 (CA125) is a protein that in humans is encoded by the MUC16 gene. , CA125 is a member of the mucin family glycoproteins which was extensive used as a tumor marker or biomarker. Many studies have demonstrated that the serum level of CA125 was elevated in some patients with specific types of cancers including ovarian cancer.  However, the potential role of CA125 for the detection of ovarian cancer is not conclusive. To further evaluate the clinical value of serum CA125 for the diagnosis of ovarian cancer, we searched and included the published studies related to the serum CA125 in the detection of ovarian cancer in this meta-analysis.
| > Materials and methods|| |
Data sources and search strategy
The database of PubMed, Wanfang and CNKI were searched. Reference lists of the relevant studies were also reviewed manually. Publication languages were limited to English and Chinese and the subjects included in the individual article were restricted to Chinese. Two authors (XYL and CG) independently reviewed the search results based on the titles and abstracts. The full texts of selected articles were reviewed independently by another author (GJH) to determine the inclusion. Disagreements were resolved by discussion. The search words were as follows: Ovarian cancer; CA125/CA125; diagnosis.
Articles investigated serum CA125 as diagnostic tests for diagnosis of ovarian cancer were included if: (1) The study design were cross-sectionl study; (2) the ovarian cancer patients were confirmed by gold diagnosis standard; (3) patients were Chinese; (4) the published language were English or Chinese; (5) sufficient data can be extracted from the individual article to reconstruct fourfold table.
The first author name, year of publication, total number of included article, number of true positive, number of false positive; number of false negative and number of true negative were all extracted from the individual paper by two reviewer (XYL and GJH) independently.
Statistical analysis was conducted using Meta-DiSc statistical software, version 1.4 (Unit of Clinical Biostatistics, Ramony Cajal Hospital, Madrid, Spain). The sensitivity, specificity, positive likelihood ratio (+LR) and negative likelihood ratio (−LR) were pooled by meta-analysis. The I 2 -test was used to evaluate whether variations were caused by heterogeneity or sampling errors (chance). Fixed-effect method was used if the no statistical heterogeneity was found in the results. Otherwise, random-effect model was used to pool the results.
| > Results|| |
According to the inclusion criteria, 19 literatures ,,,,,,,,,,,,,,,,,, were included in this meta-analysis. The total number of subjects included were 2426. The diagnostic sensitivity ranged from 0.64 to 0.84 and the diagnostic specificity ranged from 0.48 to 1.00. The detailed information of a single study was showed in [Table 1].
|Table 1: The information of the included literatures of this meta-analysis |
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No statistical heterogeneity for diagnostic sensitivity (I 2 = 0.0%) and negative likely hood ratio (−LR) (I 2 = 0.0) was found. The pooled sensitivity, −LR were calculated by fixed effected model. And significant heterogeneity for specificity (I 2 = 88.2), +LR (I 2 = 85.7%) and diagnostic odds ratio (DOR) (66.8%) were existed among the included studies. The pooled specificity, +LR and DOR were calculated by randomized effects model. The meta-analysis showed that the pooled sensitivity, specificity, +LR, −LR and DOR were 0.75 (95% confidence interval = 0.73-0.78), 0.80 (0.77-0.82), 4.52 (3.27-6.26), 0.31 (0.28-0.35) and 15.76 (10.45-23.75) respectively.
Summary receiver operating characteristic curve
The largest area of diagnosis under the summary receiver operator curve for CA125 in the detection of ovarian cancer was 0.84 demonstrated in [Figure 1].
|Figure 1: The area under the summary receiver operating characteristic curve for evaluation the diagnosis valve of cancer antigen 125 for ovarian cancer|
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| > Discussion|| |
Ovarian cancer is the leading cause of death from gynecologic cancer in the United States. And it is estimated that 21,990 new cases of ovarian cancer was diagnosis and 15,460 deaths was found in the year of 2011. For China, the crude incidence rate of ovary cancer was 7.91/100,000 and the age-adjusted rate was 5.35/100,000 during period 1999-2010 according to Wang et al.  Both the crude and age-adjusted incidence rates in urban area were substantially higher than that in rural area, the crude rate in urban region was 2.7 times of the rate in rural region and the age-adjusted rate was 2.4 times of that.  However, no exact number of ovarian patients diagnosed was reported in China.
Most of the ovarian cancer patients were in an advanced stage when diagnosed. They have lost the opportunity for operation. Tumor biomarker can be detected in the peripheral blood, which could be used for tumor diagnosis and treatment response index. CA125 is the most frequently used biomarker for ovarian cancer detection.  Medical societies, including American Congress of Obstetricians and Gynecologists recommend against women with average risk of ovarian cancer having routine CA125 examination.
Gupta et al. reported that about 90% advanced ovarian cancer patients have elevated serum levels of CA125, which indicated that CA125 could be a potential diagnostic tool for detecting ovarian cancer after the onset of symptoms.  In our meta-analysis, we evaluated the serum CA125 as a biomarker for diagnosis of ovarian cancer by pooling the sensitivity and specificity. The results showed that the summary sensitivity and specificity were 0.7 and 0.80 with its AUC of 0.84, which indicated the diagnosis value of serum CA125 for ovarian cancer was general acceptable.
| > References|| |
Yin BW, Lloyd KO. Molecular cloning of the CA125 ovarian cancer antigen: Identification as a new mucin, MUC16. J Biol Chem 2001;276:27371-5.
Yin BW, Dnistrian A, Lloyd KO. Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene. Int J Cancer 2002;98:737-40.
Bast RC Jr, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB. CA 125: The past and the future. Int J Biol Markers 1998;13:179-87.
Chen DX, Schwartz PE, Li XG, Yang Z. Evaluation of CA 125 levels in differentiating malignant from benign tumors in patients with pelvic masses. Obstet Gynecol 1988;72:23-7.
Wang MJ, Qi J, Wang H, Li XX, Wei BJ, Fu C, et al.
Diagnostic value of combining detection of human epididymis protein 4 and CA125 in patients with malignant ovarian carcinoma. Zhonghua Zhong Liu Za Zhi 2011;33:540-3.
Liu GR, Wang AL, Liu Q. Combined detection of serum CA125 and human epididymis protein 4 levels in ovarian cancer. Chin J Clin Lab Sci 2010;28:119-21.
Hu XT, Li LJ, Gao JQ. Values of human sapiens epididymis specific protein 4 combined with carbohydrate antigen 125 in diagnosis of human ovarian cancer. China Gen Pract 2011;14:2411-3.
Jing XG, Wan GJ, Pei YX. Clinical value of serum CA125 and CA123 combined with HE4 detection in the diagnosis of epithelial ovarian cancer. Acta Acad Med Mil Tertia 2011;33:644-5.
Yang C, Song ML, Zhong HB. The differential diagnostic value of HE4, CA125 and the risk of ovarian malignancy algorithm in ovarian tumor. Suzhou Univ J Med Sci 2010;30:795-8.
Ou J, Zhang XX, Wang CC. Detection of serum human epididymis protein 4 and its significance in diagnosis of ovarian cancer. J Jilin Univ Med Educ 2010;36:543-5.
Luo XH, Du ZH, Pan KY, Wang Y, Zeng HY. The value of combined serum CA125, CA199 and CEA test for ovarian tumors diagnosis. Int J Clin Exp Med 2006;5:878-9.
Shao LJ, Xue RL, Hu Y. The diagnosis value of serum CA125, CA199 and CEA for ovarian cancer. J Radioimmunol 2007;20:92-3.
Song XL, Wang GS, Luo JM, Zhao ZL. Serum CA125 combined weith CA199 in the diagnosis of ovarian cancer. J Henan Univ (Med Sci) 2007;26:70-1.
Luo XB. Value of combined detection of CA125, CA19-9 and CEA for diagnosis of ovarian carcinoma. China Healthc Innov 2009;04:77-8.
Huang F. The clinical value of CA125 combined with CA199 in the diagnosis of ovarian carcinoma. Guangxi Med J 2010;32:424-5.
Li L, Liu XX. The clinical diagnostic value of joint inspection of Serum CEA CA19-9 CA125 in the patients with ovarian cancer. J Mod Clin Med 2010;36:122-4.
Pu ZY, Liu FJ, Liu YY. Clinical research of combined detection of CA125 and CA199 in the diagnosis of ovarian cancer. West China Med J 2010; 23:1879-80.
Ming Q, Yang JJ, Wang XH, Song XC. Diagnosis and prognosis value of the serum CA125 CA199 CEA detection in patients with epithelinl ovarian cancer. China Pract Med 2010;05:53-4.
Liu L, Zhang MK, Chen JL, HRQ. The significance of serum CA125, 199 and CEA test in the diagnosis of ovarian cancer. Chongqing Med 2011;40:2423-4,6.
Wang J. Three tumor marker combined detection in the diagnosis of ovarian cancer. Chin J Coal Ind Med 2011;14:985-6.
Yu B. Serum biomarker CEA, CA125 and CA199 in the diagnosis of ovarian cancer. J Binzhou Med Univ 2011;4:294-5.
Zhang FL. Serum level of CEA, CA125 and CA199 combination in the diagnosis of ovarian cancer. Chin J Misdiagnostics 2011;11:4646-7.
Wang B, Liu SZ, Zheng RS, Zhang F, Chen WQ, Sun XB. Time trends of ovarian cancer incidence in china. Asian Pac J Cancer Prev 2014;15:191-3.
Suh KS, Park SW, Castro A, Patel H, Blake P, Liang M, et al.
Ovarian cancer biomarkers for molecular biosensors and translational medicine. Expert Rev Mol Diagn 2010;10:1069-83.
Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: A systematic review of the epidemiological literature. Nutr J 2010;9:69.