FOXC2 and CLIP4: A potential biomarker for synchronous metastasis of ≤7-cm clear cell renal cell carcinomas

Jinwoo Ahn, Kyung Seok Han, Jun Hyeok Heo, Duhee Bang, You Hyun Kang, Hyun A. Jin, Sung Joon Hong, Ji Hyun Lee, Won Sik Ham

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Renal cell carcinomas (RCC) smaller than 7-cm are heterogeneous and exhibit metastatic potential in approximately 15% of cases. Although large-scale characterization of mutations in clear cell RCC (ccRCC), the most common RCC subtype, has been established, the genetic alterations related to ≤7-cm ccRCCs undergoing synchronous metastasis are poorly understood. To discover biomarkers that can be used to estimate the risk of synchronous metastasis in these ccRCC patients, we performed whole exome sequencing on the formalin-fixed paraffin-embedded (FFPE) samples of 10 ccRCC patients with ≤7-cm tumors and synchronous metastasis and expanded our study using The Cancer Genome Atlas (TCGA) ccRCC dataset (n = 201). Recurrent mutations were selected according to functional prediction and statistical significance. Mutations in three candidate genes, RELN (1 out of 10), FOXC2 (1 out of 10), and CLIP4 (2 out of 10) were found in expanded analysis using a TCGA cohort. Furthermore, siRNA-mediated target gene knockdown (FOXC2 and CLIP4) and overexpression (RELN) assays showed that FOXC2 and CLIP4 significantly increased cell migration and viability in ccRCCs. Our study demonstrated that FOXC2 and CLIP4 activity correlates to the presence of ≤7-cm ccRCCs with synchronous metastasis and may be potential molecular predictors of synchronous metastasis of ≤7-cm ccRCCs.

Original languageEnglish
Pages (from-to)51423-51434
Number of pages12
JournalOncotarget
Volume7
Issue number32
DOIs
Publication statusPublished - 2016 Aug 1

Fingerprint

Renal Cell Carcinoma
Biomarkers
Neoplasm Metastasis
Atlases
Mutation
Genome
Gene Knockdown Techniques
Exome
Neoplasms
Paraffin
Formaldehyde
Small Interfering RNA
Cell Movement
Cell Survival
Genes
Clear-cell metastatic renal cell carcinoma

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Ahn, Jinwoo ; Han, Kyung Seok ; Heo, Jun Hyeok ; Bang, Duhee ; Kang, You Hyun ; Jin, Hyun A. ; Hong, Sung Joon ; Lee, Ji Hyun ; Ham, Won Sik. / FOXC2 and CLIP4 : A potential biomarker for synchronous metastasis of ≤7-cm clear cell renal cell carcinomas. In: Oncotarget. 2016 ; Vol. 7, No. 32. pp. 51423-51434.
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Ahn, J, Han, KS, Heo, JH, Bang, D, Kang, YH, Jin, HA, Hong, SJ, Lee, JH & Ham, WS 2016, 'FOXC2 and CLIP4: A potential biomarker for synchronous metastasis of ≤7-cm clear cell renal cell carcinomas', Oncotarget, vol. 7, no. 32, pp. 51423-51434. https://doi.org/10.18632/oncotarget.9842

FOXC2 and CLIP4 : A potential biomarker for synchronous metastasis of ≤7-cm clear cell renal cell carcinomas. / Ahn, Jinwoo; Han, Kyung Seok; Heo, Jun Hyeok; Bang, Duhee; Kang, You Hyun; Jin, Hyun A.; Hong, Sung Joon; Lee, Ji Hyun; Ham, Won Sik.

In: Oncotarget, Vol. 7, No. 32, 01.08.2016, p. 51423-51434.

Research output: Contribution to journalArticle

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AU - Ahn, Jinwoo

AU - Han, Kyung Seok

AU - Heo, Jun Hyeok

AU - Bang, Duhee

AU - Kang, You Hyun

AU - Jin, Hyun A.

AU - Hong, Sung Joon

AU - Lee, Ji Hyun

AU - Ham, Won Sik

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