Risk Prediction Tool for Aggressive Tumors in Clinical T1 Stage Clear Cell Renal Cell Carcinoma Using Molecular Biomarkers

Jee Soo Park, Hyo Jung Lee, Namhoon Cho, Jongchan Kim, Won Sik Jang, Ji Eun Heo, Won Sik Ham

Research output: Contribution to journalArticle

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Abstract

Some early-stage clear cell renal cell carcinomas (ccRCCs) of ≤7 cm are associated with a poor clinical outcome. In this study, we investigated molecular biomarkers associated with aggressive clinical T1 stage ccRCCs of ≤7 cm, which were used to develop a risk prediction tool toward guiding the decision of treatment. Among 1069 nephrectomies performed for ccRCC of ≤7 cm conducted between January 2008 and December 2014, 177 cases with available formalin-fixed paraffin-embedded tissue were evaluated. An aggressive tumor was defined as a tumor exhibiting synchronous metastasis, recurrence, or leading to cancer-specific death. Expression levels of six genes (FOXC2, CLIP4, PBRM1, BAP1, SETD2, and KDM5C) were measured by reverse-transcription polymerase chain reaction (qRT-PCR) and their relation to clinical outcomes was investigated. Immunohistochemistry was performed to validate the expression profiles of selected genes significantly associated with clinical outcomes in multivariate analysis. Using these genes, we developed a prediction model of aggressive ccRCC based on logistic regression and deep-learning methods. FOXC2, PBRM1, and BAP1 expression levels were significantly lower in aggressive ccRCC than non-aggressive ccRCC both in univariate and multivariate analysis. The immunohistochemistry result demonstrated the significant downregulation of FOXC2, PBRM1, and BAP1 expression in aggressive ccRCC. Adding immunohistochemical staining results to qRT-PCR, the aggressive ccRCC prediction models had the area under the curve (AUC) of 0.760 and 0.796 and accuracy of 0.759 and 0.852 using the logistic regression method and deep-learning method, respectively. Use of these biomarkers and the developed prediction model can help stratify patients with clinical T1 stage ccRCC.

Original languageEnglish
Pages (from-to)371-377
Number of pages7
JournalComputational and Structural Biotechnology Journal
Volume17
DOIs
Publication statusPublished - 2019 Jan 1

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Biomarkers
Renal Cell Carcinoma
Tumors
Cells
Polymerase Chain Reaction
Genes
Multivariate Analysis
Logistic Models
Immunohistochemistry
Learning
Logistics
Neoplasms
Nephrectomy
Transcriptome
Paraffin
Formaldehyde
Reverse Transcription
Area Under Curve
Polymerase chain reaction
Transcription

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Computer Science Applications

Cite this

Park, Jee Soo ; Lee, Hyo Jung ; Cho, Namhoon ; Kim, Jongchan ; Jang, Won Sik ; Heo, Ji Eun ; Ham, Won Sik. / Risk Prediction Tool for Aggressive Tumors in Clinical T1 Stage Clear Cell Renal Cell Carcinoma Using Molecular Biomarkers. In: Computational and Structural Biotechnology Journal. 2019 ; Vol. 17. pp. 371-377.
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title = "Risk Prediction Tool for Aggressive Tumors in Clinical T1 Stage Clear Cell Renal Cell Carcinoma Using Molecular Biomarkers",
abstract = "Some early-stage clear cell renal cell carcinomas (ccRCCs) of ≤7 cm are associated with a poor clinical outcome. In this study, we investigated molecular biomarkers associated with aggressive clinical T1 stage ccRCCs of ≤7 cm, which were used to develop a risk prediction tool toward guiding the decision of treatment. Among 1069 nephrectomies performed for ccRCC of ≤7 cm conducted between January 2008 and December 2014, 177 cases with available formalin-fixed paraffin-embedded tissue were evaluated. An aggressive tumor was defined as a tumor exhibiting synchronous metastasis, recurrence, or leading to cancer-specific death. Expression levels of six genes (FOXC2, CLIP4, PBRM1, BAP1, SETD2, and KDM5C) were measured by reverse-transcription polymerase chain reaction (qRT-PCR) and their relation to clinical outcomes was investigated. Immunohistochemistry was performed to validate the expression profiles of selected genes significantly associated with clinical outcomes in multivariate analysis. Using these genes, we developed a prediction model of aggressive ccRCC based on logistic regression and deep-learning methods. FOXC2, PBRM1, and BAP1 expression levels were significantly lower in aggressive ccRCC than non-aggressive ccRCC both in univariate and multivariate analysis. The immunohistochemistry result demonstrated the significant downregulation of FOXC2, PBRM1, and BAP1 expression in aggressive ccRCC. Adding immunohistochemical staining results to qRT-PCR, the aggressive ccRCC prediction models had the area under the curve (AUC) of 0.760 and 0.796 and accuracy of 0.759 and 0.852 using the logistic regression method and deep-learning method, respectively. Use of these biomarkers and the developed prediction model can help stratify patients with clinical T1 stage ccRCC.",
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Risk Prediction Tool for Aggressive Tumors in Clinical T1 Stage Clear Cell Renal Cell Carcinoma Using Molecular Biomarkers. / Park, Jee Soo; Lee, Hyo Jung; Cho, Namhoon; Kim, Jongchan; Jang, Won Sik; Heo, Ji Eun; Ham, Won Sik.

In: Computational and Structural Biotechnology Journal, Vol. 17, 01.01.2019, p. 371-377.

Research output: Contribution to journalArticle

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