Sains Malaysiana 44(12)(2015): 1671–1676

 

Performance Comparison of Serum and Urine Biomarkers from Independent Samples for Ovarian Cancer Screening

(Perbandingan Prestasi Serum dan Penanda Biologi Urin daripada Sampel Bebas untuk Saringan Kanser Ovari)

 

HYE-JEONG SONG1,3, KI-SEOK JEONG2,3, JONG-DAE KIM1,3, CHAN-YOUNG PARK1,3 & YU-SEOP KIM*1,3

 

1Department of Ubiquitous Computing, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Korea

 

2Department of Computer Engineering, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Korea

 

3Bio IT Research Center, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Korea

 

Received: 2 September 2014/Accepted: 23 June 2015

 

ABSTRACT

This study compares the diagnostic performance of urine and serum multiple biomarkers for early diagnosis of ovarian cancer. The sample population includes 119 benign and 101 ovarian cancer patients. The marker combinations used to compare performance include 16 markers whose concentration values were obtained using the Luminex assay. In order to identify an optimal marker combination that could classify ovarian cancer and benign patients, the area under the curve (AUC) is used to evaluate 2-, 3-, and 4-marker combinations and the classification is performed by using logistic regression. In the case of urine samples, the best AUC values are 87.89% for the 2 protein markers combination, 90.22% for the 3 markers combination and 92.43% for the 4 marker combination. In contrast, the best AUC values for serum sample are 92.4% for the 2 marker combination, 93.63% for the 3 marker combination and 94.63% for the 4 marker combination. This study confirmed that combining multiple biomarkers could improve diagnostic accuracy. Even though urine sample shows relatively lower performance than serum, the urine could be utilized more widely for its simple usability.

 

Keywords: Biomarker; ovarian cancer; serum; urine

 

ABSTRAK

Kajian ini membandingkan prestasi diagnostik air kencing dan beberapa penanda biologi serum untuk diagnosis awal kanser ovari. Gabungan penanda digunakan untuk membandingkan prestasi 16 penanda dan nilai kepekatan diperoleh dengan menggunakan logam penguji Luminex. Untuk menentukan gabungan penanda optimum yang boleh mengenal pasti kanser ovari dan pesakit biasa, luas di bawah lengkungan (AUC) digunakan untuk menilai kombinasi penanda 2-, 3- dan 4-. Pengelasan dijalankan dengan menggunakan regresi logistik. Dalam kes sampel air kencing, nilai AUC yang terbaik adalah 87.89% untuk 2 kombinasi penanda protein, 90.22% untuk 3 kombinasi penanda dan 92.43% untuk 4 kombinasi penanda. Sebaliknya, nilai AUC yang terbaik untuk sampel serum adalah 92.4% untuk 2 kombinasi penanda, 93.63% untuk 3 kombinasi penanda dan 94.63% untuk 4 kombinasi penanda. Kajian ini mengesahkan bahawa gabungan beberapa penanda biologi boleh meningkatkan ketepatan diagnostik. Walaupun sampel air kencing menunjukkan prestasi yang agak rendah daripada serum, air kencing boleh digunakan dengan lebih meluas untuk kebolehgunaan yang mudah.

 

Kata kunci: Air kencing; kanser ovari; penanda biologi; serum

 

REFERENCES

American Cancer Society. http://www.cancer.org/Cancer/ OvarianCancer.

Amonkar, S.D., Bertenshaw, G.P., Chen, T.H., Bergstrom, K.J., Zhao, J., Seshaiah, P., Yip, P. & Mansfield, B.C. 2009. Development and preliminary evaluation of a multivariate index assay for ovarian cancer. PLoS One 4: 1-11.

ASAN Medical Center. 2010. http://eng.amc.seoul.kr/lang/ AboutAMCController.do?forward=/jsp/en/AMCMain. jsp&sslpage=http%3A//medical.amc.seoul.kr/medservice/ main/main.do.

Borgia, J.A., Basu, S., Faber, L.P., Kim, A.W., Coon, J.S., Kaiser- Walters, K.A., Fhied, C., Thomas, S., Rouhi, O., Warren, W.H., Bonomi, P. & Liptay, M.J. 2009. Establishment of a multi-analyte serum biomarker panel to identify lymph node metastases in non-small cell lung cancer. Journal of Thoracic Oncology 4(3): 338-347.

Chatterjee, S. & Zetter, B. 2005. Cancer biomarkers: Knowing the present and predicting the future. Future Oncology 1(1): 37-50.

Feng, Q., Yu, M. & Kiviat, N. 2006. Molecular biomarkers for cancer detection in blood and bodily fluid. Critical Reviews in Clinical Laboratory Sciences 43(5-4): 497-560.

Food and Drug Administration. 2007. Draft Guidance for Industry, Clinical Laboratories, and FDA Staff. In vitro Diagnostric Multivariate Index Assays. Rockville, MD: U.S. Department of Health and Human Services. pp. 1-15.

Hellstrom, I., Heagerty, P.J., Swisher, E., Liu, P., Jaffar, J., Agnew, K. & Hellstrom, K.E. 2010. Detection of the HE4 pretein in urine as a biomarker for ovarian neoplasms. Cancer Letters 296: 43-48.

Jung, S., Oh, E.J., Yang, C.W., Ahn, W.S., Kim, Y., Park, Y.J. & Han, K. 2009. Comparative evaluation of ELISA and Luminex panel reactive antibody assays for HLA alloantibody screening. Korean Journal Laboratory Medicine 29: 473-480.

Kim, Y., Koo, I., Jung, B.H., Chung, B.C. & Lee, D. 2010. Multivariate classification of urine metabolome profiles for breast cancer diagnosis. BMC Bioinformatics 11: 1-9.

Kohavi, R. 1995. A study of cross-validation and bootstrap for accuracy estimation and model selection. International Joint Conference on Artificial Intelligence 14(2): 1137-1145.

Moore, R.G., Brown, A.K., Miller, M.C., Skates, S., Allard, W.J., Verch, T., Steinhoff, M., Messerlian, G., DiSilvesto, P., Granai, C.O. & Bast. R.C. Jr. 2008. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol. Oncology 108: 402-408.

Nolen, B., Marrangoni, A., Velikokhatnaya, L., Prosser, D., Winans, M., Gorelik, E. & Lokshin, A. 2009. A serum based analysis of ovarian epithelial tumorigenesis. Gynecologic Oncology 112(1): 47-54.

Nolen, B.M. & Lokshin, A.E. 2012. Multianalyte assay systems in the differential diagnosis of ovarian cancer. Expert Opinion on Medical Diagnostics 6(2): 131-138.

Pepe, M.S., Cai, T. & Longton, G. 2006. Combining predictors for classification using the area under the receiver operating characteristic curve. Biometric 62: 221-229.

Petri, A.L., Simonsen, A.H., Høgdall, E., Christensen, I.J., Kjaer, S.K., Yip, C., Risum, S., Pedersen, A.T., Hartwell, D., Fung, E.T. & Høgdall, C. 2010. Comparison of proteomic biomarker panels in urine and serum for ovarian cancer diagnosis. Proteomics-Clinical Applications 4(3): 304-314.

Saeys, Y., Inza, I. & Larranaga, P. 2007. A review of feature selection techniques in bioinformatics. Bioinformatics 23(19): 2507-2517.

Yukovetsky, Z., Skates, S., Lomakin, A., Nolen, B., Pulsipher, T., Modugno, F., Marks, J., Godwin, A., Gorelik, E., Jacobs, I., Menon, U., Lu, K., Badgwell, D., Bast, R.J. & Lokshin, A. 2013. Development of a multimarker assay for early detection of ovarian cancer. Journal of Clinical Oncology 28(13): 2159-2166.

Zhang, Z. 2012. An in vitro diagnostic multivariate index assay (IVDMIA) for ovarian cancer: Harvesting the power of multiple biomarkers. Reviews in Obstetrics & Gynecology 5(1): 35-41.

 

*Corresponding author; email: yskim01@hallym.ac.kr

 

 

 

previous