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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
FOXC2 and CLIP4 : a potential biomarker for synchronous metastasis of ≤7-cm clear cell renal cell carcinomas
Jinwoo Ahn1, Kyung Seok Han2, Jun Hyeok Heo3
1Department of Chemistry, Yonsei University, Seoul, Korea.
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.
Insights
Researchers identified FOXC2 and CLIP4 gene mutations as potential predictors of metastasis in small clear cell renal cell carcinomas (ccRCC). These findings may help estimate metastasis risk in ccRCC patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Renal cell carcinoma (RCC), particularly clear cell RCC (ccRCC), is heterogeneous, with small tumors (<7 cm) potentially metastasizing.
- Genetic alterations driving metastasis in small ccRCCs are not well understood.
- Identifying biomarkers for metastasis risk in ccRCC is crucial for patient management.
Purpose of the Study:
- To discover genetic biomarkers for predicting synchronous metastasis in ccRCC patients with tumors ≤7 cm.
- To investigate the role of specific gene mutations in ccRCC metastasis.
Main Methods:
- Whole exome sequencing of formalin-fixed paraffin-embedded (FFPE) ccRCC samples from patients with synchronous metastasis.
- Analysis of The Cancer Genome Atlas (TCGA) ccRCC dataset for recurrent mutations.
- Functional assays including siRNA-mediated gene knockdown and overexpression.
Main Results:
- Recurrent mutations in RELN, FOXC2, and CLIP4 were identified in ccRCCs with synchronous metastasis.
- FOXC2 and CLIP4 gene activity significantly increased cell migration and viability in ccRCC cells.
- FOXC2 and CLIP4 activity correlates with the presence of synchronous metastasis in ccRCCs ≤7 cm.
Conclusions:
- FOXC2 and CLIP4 are potential molecular predictors of synchronous metastasis in small ccRCCs.
- These genes may serve as biomarkers to estimate metastasis risk in ccRCC patients.
- Further research is warranted to validate these findings for clinical application.
