Identifying molecular genetic features and oncogenic pathways of clear cell renal cell carcinoma through the anatomical (PADUA) scoring system
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Hui Zhu1,*, Haoyan Chen2,*, Zhiqian Lin3, Guohai Shi4, Xiaozhu Lin5, Zhiyuan Wu5, Xia Zhang6, Xi Zhang7
1Department of Radiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
2State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Institute for Digestive Diseases, Shanghai Jiao-Tong University School of Medicine, Shanghai 200001, China
3Department of Radiology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200001, China
4Department of Urology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
5Department of Radiology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
6Department of Oncology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
7Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269-3156, USA
*These authors contributed equally to this work
Hui Zhu, e-mail: firstname.lastname@example.org
Haoyan Chen, e-mail: email@example.com
Xi Zhang, e-mail: firstname.lastname@example.org
Keywords: renal cell carcinoma, PADUA, gene mutation, miRNA subtypes, oncogenic pathways
Received: August 22, 2015 Accepted: January 19, 2016 Published: February 02, 2016
Although the preoperative aspects and dimensions used for the PADUA scoring system were successfully applied in macroscopic clinical practice for renal tumor, the relevant molecular genetic basis remained unclear. To uncover meaningful correlations between the genetic aberrations and radiological features, we enrolled 112 patients with clear cell renal cell carcinoma (ccRCC) whose clinicopathological data, genomics data and CT data were obtained from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA). Overall PADUA score and several radiological features included in the PADUA system were assigned for each ccRCC. Despite having observed no significant association between the gene mutation frequency and the overall PADUA score, correlations between gene mutations and a few radiological features (tumor rim location and tumor size) were identified. A significant association between rim location and miRNA molecular subtypes was also observed. Survival analysis revealed that tumor size > 7 cm was significantly associated with poor survival. In addition, Gene Set Enrichment Analysis (GSEA) on mRNA expression revealed that the high PADUA score was related to numerous cancer-related networks, especially epithelial to mesenchymal transition (EMT) related pathways. This preliminary analysis of ccRCC revealed meaningful correlations between PADUA anatomical features and molecular basis including genomic aberrations and molecular subtypes.
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