Development of Response Classifier for Vascular Endothelial Growth Factor Receptor (VEGFR)-Tyrosine Kinase Inhibitor (TKI) in Metastatic Renal Cell Carcinoma

Heounjeong Go, Mun Jung Kang, Pil Jong Kim, Jae Lyun Lee, Ji Y. Park, Ja Min Park, Jae Y. Ro, Yong Mee Cho

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Vascular endothelial growth factor receptor (VEGFR)-targeted therapy improved the outcome of metastatic renal cell carcinoma (mRCC) patients. However, a prediction of the response to VEGFR-tyrosine kinase inhibitor (TKI) remains to be elucidated. We aimed to develop a classifier for VEGFR-TKI responsiveness in mRCC patients. Among 101 mRCC patients, ones with complete response, partial response, or ≥24 weeks stable disease in response to VEGFR-TKI treatment were defined as clinical benefit group, whereas patients with <24 weeks stable disease or progressive disease were classified as clinical non-benefit group. Clinicolaboratory-histopathological data, 41 gene mutations, 20 protein expression levels and 1733 miRNA expression levels were compared between clinical benefit and non-benefit groups. The classifier was built using support vector machine (SVM). Seventy-three patients were clinical benefit group, and 28 patients were clinical non-benefit group. Significantly different features between the groups were as follows: age, time from diagnosis to TKI initiation, thrombocytosis, tumor size, pT stage, ISUP grade, sarcomatoid change, necrosis, lymph node metastasis and expression of pAKT, PD-L1, PD-L2, FGFR2, pS6, PDGFRβ, HIF-1α, IL-8, CA9 and miR-421 (all, P < 0.05). A classifier including necrosis, sarcomatoid component and HIF-1α was built with 0.87 accuracy using SVM. When the classifier was checked against all patients, the apparent accuracy was 0.875 (95% CI, 0.782–0.938). The classifier can be presented as a simple decision tree for clinical use. We developed a VEGFR-TKI response classifier based on comprehensive inclusion of clinicolaboratory-histopathological, immunohistochemical, mutation and miRNA features that may help to guide appropriate treatment in mRCC patients.

Original languageEnglish (US)
Pages (from-to)51-58
Number of pages8
JournalPathology and Oncology Research
Volume25
Issue number1
DOIs
StatePublished - Jan 15 2019

Keywords

  • Machine learning
  • Metastatic renal cell carcinoma
  • Response classifier
  • Tyrosine kinase inhibitors
  • Vascular endothelial growth factor signaling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Cancer Research

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