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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 
 ONCOTARGET , Vol.7(32) : 51423-51434, 2016 
Journal Title
Issue Date
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; iomarkers, Tumor/physiology ; Carcinoma, Renal Cell/genetics* ; Carcinoma, Renal Cell/pathology* ; Carrier Proteins/genetics ; Carrier Proteins/physiology* ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Female ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/physiology* ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms/genetics* ; Kidney Neoplasms/pathology* ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Tumor Burden/genetics*
CLIP4 ; FOXC2 ; clear cell renal cell carcinoma (ccRCC) ; metastasis ; whole exome sequencing
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.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Ham, Won Sik(함원식) ORCID logo https://orcid.org/0000-0003-2246-8838
Hong, Sung Joon(홍성준) ORCID logo https://orcid.org/0000-0001-9869-065X
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