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

doi:10.18632/oncotarget.9842

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

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

13 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 language	English
Pages (from-to)	51423-51434
Number of pages	12
Journal	Oncotarget
Volume	7
Issue number	32
DOIs	https://doi.org/10.18632/oncotarget.9842
Publication status	Published - 2016 Aug 1

Bibliographical note

Funding Information:
This study was supported by a research grant from the Korean Prostate Research Foundation (grant number: 4-2014-0021; to WSH), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (grant number: HI13C2163; to DHB), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and future Planning (grant number: NRF-2015R1A2A2A03006577; to JHL), and the NRF (grant number: 2013R1A1A1005025; to KSH).

All Science Journal Classification (ASJC) codes

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.9842

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@article{c4a69e6455e34de2a29122a31da0b7d1,

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

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.",

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

note = "Funding Information: This study was supported by a research grant from the Korean Prostate Research Foundation (grant number: 4-2014-0021; to WSH), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (grant number: HI13C2163; to DHB), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and future Planning (grant number: NRF-2015R1A2A2A03006577; to JHL), and the NRF (grant number: 2013R1A1A1005025; to KSH).",

year = "2016",

month = aug,

day = "1",

doi = "10.18632/oncotarget.9842",

language = "English",

volume = "7",

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TY - JOUR

T1 - FOXC2 and CLIP4

T2 - A potential biomarker for synchronous metastasis of ≤7-cm clear cell renal cell carcinomas

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

N1 - Funding Information: This study was supported by a research grant from the Korean Prostate Research Foundation (grant number: 4-2014-0021; to WSH), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (grant number: HI13C2163; to DHB), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and future Planning (grant number: NRF-2015R1A2A2A03006577; to JHL), and the NRF (grant number: 2013R1A1A1005025; to KSH).

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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