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Intraoperative Diagnosis Support Tool for Serous Ovarian Tumors Based on Microarray Data Using Multicategory Machine Learning
  1. Jee Soo Park, BS*,,
  2. Soo Beom Choi, MS*,,
  3. Hee Jung Kim, PhD§,
  4. Nam Hoon Cho, MD, PhD,
  5. Sang Wun Kim, MD, PhD§,
  6. Young Tae Kim, MD, PhD§,
  7. Eun Ji Nam, MD, PhD§,
  8. Jai Won Chung, BS*, and
  9. Deok Won Kim, PhD*,
  1. *Department of Medical Engineering, Yonsei University College of Medicine;
  2. Department of Medicine, Yonsei University College of Medicine, Seoul, Korea;
  3. Graduate Program in Biomedical Engineering, Yonsei University, Seoul, Korea; and Department of
  4. §Obstetrics and Gynecology and
  5. Pathology, Yonsei University College of Medicine, Seoul, Korea.
  1. Address correspondence and reprint requests to Deok Won Kim, PhD, Department of Medical Engineering, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea. E-mail: kdw@yuhs.ac.

Abstract

Objectives Serous borderline ovarian tumors (SBOTs) are a subtype of serous ovarian carcinoma with atypical proliferation. Frozen-section diagnosis has been used as an intraoperative diagnosis tool in supporting the fertility-sparing surgery by diagnosing SBOTs with accuracy of 48% to 79%. Using DNA microarray technology, we designed multicategory classification models to support frozen-section diagnosis within 30 minutes.

Materials and Methods We systematically evaluated 6 machine learning algorithms and 3 feature selection methods using 5-fold cross-validation and a grid search on microarray data obtained from the National Center for Biotechnology Information. To validate the models and selected biomarkers, expression profiles were analyzed in tissue samples obtained from the Yonsei University College of Medicine.

Results The best accuracy of the optimal machine learning model was 97.3%. In addition, 5 features, including the expression of the putative biomarkers SNTN and AOX1, were selected to differentiate between normal, SBOT, and serous ovarian carcinoma groups. Different expression levels of SNTN and AOX1 were validated by real-time quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry. A multinomial logistic regression model using SNTN and AOX1 alone was used to construct a simple-to-use equation that gave a diagnostic test accuracy of 91.9%.

Conclusions We identified 2 biomarkers, SNTN and AOX1, that are likely involved in the pathogenesis and progression of ovarian tumors. An accurate diagnosis of ovarian tumor subclasses by application of the equation in conjunction with expression analysis of SNTN and AOX1 would offer a new accurate diagnosis tool in conjunction with frozen-section diagnosis within 30 minutes.

  • Ovarian tumor
  • Microarray analysis
  • Artificial intelligence
  • Multicategory classification
  • Borderline tumor

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Footnotes

  • The authors declare no conflicts of interest.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).