MP08-11 RENAL VEIN OSTIUM WALL INVASION OF RENAL CELL CARCINOMA WITH AN INFERIOR VENA CAVA TUMOR THROMBUS: COMPREHENSIVE MOLECULAR CHARACTERIZATION AND ITS IMPLICATIONS FOR CLINICAL PRACTICE

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP08)1 Apr 2020MP08-11 RENAL VEIN OSTIUM WALL INVASION OF RENAL CELL CARCINOMA WITH AN INFERIOR VENA CAVA TUMOR THROMBUS: COMPREHENSIVE MOLECULAR CHARACTERIZATION AND ITS IMPLICATIONS FOR CLINICAL PRACTICE Cheng Liu*, Jianjun Yu, Mengyao Tan, Shidong Jia, and Lulin Ma Cheng Liu*Cheng Liu* More articles by this author , Jianjun YuJianjun Yu More articles by this author , Mengyao TanMengyao Tan More articles by this author , Shidong JiaShidong Jia More articles by this author , and Lulin MaLulin Ma More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000828.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal cell carcinoma (RCC) is a common cancer worldwide with up to 10% of patients accompanying intravascular tumor thrombus (TT). Patients with RCC may develop phenotypically distinct TT, some of which adhere densely to the venous wall (DATT, densely adherent TT) while some others do not adhere to the endothelium (NATT, non-adherent/minimal adherence TT). To explore whether patients with NATT or DATT can benefit more from the surgical resection and characterize molecular difference between the two groups for patient stratification and prognosis. METHODS: Clinical information and overall survival of 77 non-metastatic patients who went caval thrombectomy was retrospectively analyzed. Whole exome sequencing (WES) and whole transcriptome sequencing (WTS) were performed to profile genomic and transcriptomic landscape of matched primary and TT samples. Genomic alterations and transcriptomic profiling data were processed using public and in-house bioinformatics tools and analyzed for enriched mutations and pathways. Differentially mutated and expressed genes between DATT and NATT groups were assessed by Fisher exact test and DESeq2 respectively. TGCA expression dataset was analyzed through unsupervised hierarchical clustering. RESULTS: Patients with DATT showed worse survival after the surgical operation (Hazard Ratio: 5.1, P = 0.03). WES of tumor samples from prospectively enrolled patients revealed that VHL, PBRM1, BAP1, ARID1A and SETD2 are the most frequent mutated genes, consistent with public TCGA RCC data. Notably, SETD2, PTEN and TP53 mutations are significantly enriched in NATT patients relative to DATT. Analogously, transcriptomic profiling revealed P53 signaling pathway, DNA damage repair pathways and genes involved in tumor metastasis are upregulated in NATT. By contrast, genes related to cell-cell adhesion, blood coagulation, hypoxia, and VEGF signaling pathway are enriched in DATT samples. Interestingly, expression data from public primary RCC samples uncovered a subgroup of samples that are NATT-like harbor enriched TP53, PTEN and SETD2 mutations and have poorer progression-free survival and overall survival, suggesting that NATT may intrinsically represent a more aggressive subgroup of patients. CONCLUSIONS: Patients with non-adherent/minimal adherence TT (NATT) benefit more from surgery than that with densely adherent TT. Interestingly, molecular characterization by whole-exome and whole-transcriptomic sequencing delineated that patients with NATT harbor significantly enriched mutations in SETD2, PTEN and TP53 and may represent a more aggressive subtype. Such genes may serve as predictive biomarkers to stratify patients who can benefit most from the intervention of surgery. Source of Funding: The study was funded by Peking University Medicine Fund of Fostering Young Scholars’ Scientific & Technological Innovation BMU2018PY003; the National Natural Science Foundation of China (Nos.: 81711530048, 81572515, 81672522); Peking University Third Hospital Clinical Research Fund BYSY2018062, BYSY2018012. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e110-e110 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cheng Liu* More articles by this author Jianjun Yu More articles by this author Mengyao Tan More articles by this author Shidong Jia More articles by this author Lulin Ma More articles by this author Expand All Advertisement PDF downloadLoading ...