Volume 24, Issue 2 (June & July 2021)                   J Arak Uni Med Sci 2021, 24(2): 196-203 | Back to browse issues page


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Fini E, Nasirian N, Hosein Beigy B. Evaluating Specivity, Sensitivity, Positive and Negative Predictive Values of CA125 for Diagnosing Ovarian Cancer. J Arak Uni Med Sci 2021; 24 (2) :196-203
URL: http://jams.arakmu.ac.ir/article-1-6161-en.html
1- Department of General Practitioner, School of Medical Shahid Babaee, Qazvin University of Medical Science, Qazvin, Iran.
2- Department of Pathobiology, Shahid Babaei School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran. , qums@gmail.com
3- Department of Parasitology, Shahid Babaei School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
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1. Introduction
varian carcinoma is the most common type of ovarian cancer [1]. According to global statistics in 2012, ovarian cancer was the seventh most frequent type of cancer and the eighth leading cause of cancer-induced death in women [2]. CA125 is a member of the glycoprotein family and as a biomarker in the body, i.e., the most widely used biomarker in ovarian cancer screening [3, 4]. However, according to studies, CA125 is not very sensitive and specific to be used as a screening test in the medical community. This is because this biomarker rises in other cancers, such as the endometrium, breast, lung, etc., as well as physiological conditions such as pregnancy and menstruation. Moreover, this biomarker is not necessarily elevated in every disease with ovarian cancer [9]. It is simple and non-invasive; thus, this test is almost always performed and plays an important role in identifying women with ovarian mass in ultrasound as well as the treatment process and after treatment concerning determining the prognosis and recurrence of the disease. This study explored the relationship between high CA125 and the presence of ovarian cancer and the practical value of measuring CA125 as a screening test to determine the sensitivity, specificity, and positive and negative predictive value of this test in Iranian patients.
2. Materials and Methods   
This cross-sectional study was performed epidemiologically and descriptively with analytical aspects; all CA125 tests performed in 2018-2019 in Hospitals affiliated with the university referral center for this test in Qazvin Province, Iran, were examined for ovarian cancer. In addition, CA125 levels were compared between healthy individuals and patients with ovarian cancer.
CA125 was measured using the Electrochemiluminescence (ECL) method, i.e., the most accurate method of performing this test. Besides, it was performed by an experienced individual by a Roch kit in a single laboratory. The normal values of CA125 were considered to range between 0-35 U/mL.
Next, a checklist was prepared in which patients’ data, including age, complaints, diagnosis, and CA125 were recorded. Finally, the obtained data were analyzed in SPSS.
Descriptive findings were also extracted. T-test was used to compare the mean age and the relationship between a positive test and the presence of ovarian cancer in the study subjects. Probability values of below 0.05 were considered significant. Then, according to the collected data, sensitivity (true positive test/total patients), negative predictive value, specificity (true negative test/total healthy individuals), positive predictive value (true positive test/total positive test cases), and negative predictive value (true negative test cases/total negative test cases) were measured. All cases in which the patient was unavailable after the test and it was unclear whether or not they had ovarian cancer were excluded from the study.
3. Results
In total, 400 patients for whom the CA125 test was performed in Qazvin hospital laboratory between 2015 and 2019 were included in this study. Of them, 141(35.3%) cases had a definite diagnosis of ovarian cancer, while in the remaining 259(64.7%) subjects, ovarian cancer was ruled out with a pathological diagnosis. In general, CA125 values were negative in 167(41.8%) cases and positive in 233(58.2%) subjects.
The Mean±SD age of study participants was 57.97±17.3 years. The youngest sample was 17 years old and the oldest was 98 years old. The Mean±SD age in the group with a diagnosis of ovarian cancer was 60.14±16.6 years and in the healthy group in terms of ovarian cancer, it was 54.94±17 years. The relevant results of the Independent Samples t-test indicated that the relationship between age and serum levels of CA125 was significant (P=0.003). The relationship between CA125 levels and the diagnosis of ovarian cancer was evaluated. The relationship between these two parameters is summarized in Table 1


The Chi-squared test data revealed that the levels of CA125 were significantly correlated with ovarian cancer (P<0.0001). Finally, the parameters related to the diagnostic value of CA125 measurement were calculated to evaluate ovarian cancer. The present research results highlighted that the sensitivity of the test was equal to 80.1%, its specificity equaled 53.6%, the test’s positive predictive value and negative predictive value were measured to be 48.4% and 83%, respectively.
Sensitivity: True positive test/total patients: 141/113
Feature: True negative test/total healthy individuals: 259/139
Positive predictive value: True positive tests/Total positive test cases: 223/113
Negative predictive value: True negative test items/Total negative test items: 167139
4. Discussion and Conclusion
This study revealed that the CA125 levels as well as the age of the explored patients were significantly associated with presenting ovarian cancer. Furthermore, concerning the diagnostic value of CA125 in the study of ovarian cancer, test sensitivity was measured as 80.1%, specificity: 53.6%, positive predictive value: 48.4%, and negative predictive value: 83%. Various international and domestic studies have examined the association between CA125 and ovarian cancer. In this regard, Lycke et al. (2018) examined the diagnostic value of CA-125, HE4, and ROMA in determining the risk of ovarian mass malignancy in Sweden. They concluded that CA125 is superior to HE4 as a biomarker in identifying women with ovarian cancer [10].
Compared to the above-mentioned study, our research also signified that high levels of CA125, despite ovarian cancer, were significant correlated with a very low P-value; thus, our study data were consistent with those of Lycke and associates. Additionally, compared to the above study, although the positive predictive value in our study was lower, the sensitivity and specificity values and the negative predictive value of the test were almost consistent with the results of this study. The results of Yousefi et al.’s study (2014) indicated that the mean age of patients with malignant mass was significantly higher than that of the patients with benign mass [12].
Compared to their results, age, in our study, was significantly related to the presence of ovarian cancer; there was also a significant relationship between the presence of ovarian cancer and CA125 levels, i.e., consistent with the results of the study by Yousefi and colleagues. Besides, in a study conducted in 2015 by Pallavi Anand in India, several patients at Kanpur Hospital who presented with early signs of abdominal pain, infertility, etc. were screened with the CA125 biomarker test. Ovarian cancer rates have risen further, accordingly [13]. The results of other studies indicated the role of this biomarker in the early diagnosis of ovarian cancer. It also depends on the prognosis and response to treatment.

Ethical Considerations
Compliance with ethical guidelines

The present study was approved by the Thesis Council of Qazvin University of Medical Sciences (Ethics Code: IR.QUMS.REC.1396.316). The researchers adhered to all the principles of the protocols and guidelines recommended by the Helsinki Convention on Ethics in Research. Finally, to maintain confidentiality issues, the results of this study were reported without disclosing the names and identifiable details of patients.

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 

Authors' contributions
All authors equally contributed to preparing this article.

Conflicts of interest
The authors declared no conflicts of interest.

Acknowledgements
We would like to thank the laboratory and pathology department of Velayat Hospital for their sincere cooperation, especially with Ms. Islami, as well as Dr. Samiei and Dr. Tahvildari, who contributed to this research.

 
Refrences
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Type of Study: Original Atricle | Subject: Internal
Received: 2019/10/11 | Accepted: 2021/04/19

References
1. Noori-Daloii M R, Rashvand Z. Molecular Genetics and Gene Therapy in Ovarian Cancer. Horizon Med Sci . 2010; 16 (3) :5-19
2. Marjani M. Epidemiology and risk factors of ovarian cancer. NAIGO 2010;5(3):67-73.
3. Chavoshi S, haidari kashl S, rezaee tavirani M, ebrahimi M, etedali A, Raessodati R, et al . Tumor Markers at a Glance. SJIMU. 2013; 21 (6) :143-159
4. Sundar S, Neal RD, Kehoe S. Diagnosis of ovarian cancer. BMJ. 2015 Sep 1;351:h4443. [DOI:10.1136/bmj.h4443]
5. Nolen BM, Lokshin AE. Biomarker testing for ovarian cancer: clinical utility of multiplex assays. Mol Diagn Ther J.2013 Jun;17(3):139-46. [DOI:10.1007/s40291-013-0027-6]
6. Duraisamy S, Ramasamy S, Kharbanda S, Kufe D "Distinct evolution of the human carcinoma-associated transmembrane mucins, MUC1, MUC4 AND MUC16". Gene J May 2012; 373: 28-34. [DOI:10.1016/j.gene.2005.12.021]
7. Suh KS, Park SW, Castro A, Patel H, Blake P, Goy A. "Ovarian cancer biomarkers for molecular biosensors and translational medicine". Expert Review of Molecular Diagnostics. Nov 2010;10 (8): 1069-83 [DOI:10.1586/erm.10.87]
8. Bast RC, Klug TL, St John E, Jenison E, Niloff JM "A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer". The New England Journal of Medicine.Oct 2013;chapter 2 pp98.
9. Göcze P, Vahrson H.Ovarian carcinoma antigen (CA 125) and ovarian cancer (clinical follow-up and prognostic studies). Orvosi Hetilap J(in Hungarian). Apr 2012;10(5):35-45
10. Lycke M, Kristjansdottir B, Sundfeldt K. A multicenter clini(cal trial validating the performance of HE4, CA125, risk of ovarian malignancy algorithm and risk of malignancy index. Gynecol Oncol J. 2018 Aug 24.;pii: S0090-8258(18)31155-7. [DOI:10.1016/j.ygyno.2018.08.025]
11. Jafari Shobeiri M, Parizad Nasirkandy M, Nazari F, Ouladsahebmadarek E, Sayyah-Melli M, Mostafa Gharabaghi P, et al. Diagnostic Value of HE4, CA125 and Risk of Ovarian Malignancy Algorithm in Detecting Ovarian Cancer. IJWHR 2015; 3: 208-211 [DOI:10.15296/ijwhr.2015.43]
12. Yousefi Z, Hasanzadeh Mofrad M, Kazemianfar Z, Ayatollahi H, Tavassoli F, Beyranvandi M, et al. Comparison of Serum Levels of HSP70 and CA125 in Patients with Epithelial Ovarian Cancer and Patients with Benign Ovarian Masses. The Iranian Journal of Obstetrics, Gynecology and Infertility, 2014; 17(101): 1-5.
13. Pallavi Anand, Ipsita Choudhury A case study of assessment of CA-125 levels in the rural population of Kanpur. JMR 2015;1(5):139-141.
14. Arab M, Maktabi M, Zham H, Kimiaei P, Davalo S. Is Ovarian Mass Malignancy Prediction Accuracy Increased by Adding Serum CA125 Measurement to Sonographic Findings?. Avicenna J Clin Med. 2012; 18 (4) :37-40
15. Bashizadeh-Fakhar H, Rezaie-Tavirani M, Zali H, Faraji R, Kazem Nejad E, et al. The Diagnostic Value of Serum CEA, CA-125, and ROMA Index in Low-Grade Serous Ovarian Cancer, Int J Cancer Manag. 2018 ;11(5):e63397. [DOI:10.5812/ijcm.63397]
16. Yousefi Z, Homaei F. Risk Factors and Factors in Determining the Prognosis of Ovarian Cancer. JMCI 2006;24(3):279-88.
17. Gupta D, Lis CG. Role of CA125 in predicting ovarian cancer survival - a review of the epidemiological literature. J Ovarian Res. 2009 Oct 9;2:13. [DOI:10.1186/1757-2215-2-13]

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