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Sources of Funding: None

Introduction

Overall, 4 to 10% of newly diagnosed renal cell carcinoma (RCC) patients have been found to have a venous tumor thrombus (VTT). Intratumoral heterogeneity may contribute to progression of the disease and metastases. Previous studies have focused on studying the heterogeneity of metastases, recurrence and tumor. There has been no study to date evaluating VTT and characterizing its transcriptional profile. We report results of the transcriptional analysis of primary tumor (PT), VTT and adjacent normal parenchyma (NP).

Methods

We performed Whole Transcriptome Sequencing on fresh tissue specimens from 6 patients with clear cell RCC and VTT collected at the time of radical nephrectomy with tumor thrombectomy. We evaluated transcriptional alterations between PT/NP, VTT/NP and VTT/PT. We compared our data set with The Cancer Genome Atlas (TCGA) data. For multiple testing corrections, we utilized false discovery estimation and differential expression criterion.

Results

1. We surveyed 23,228 genes and identified differential expression in 1455, 1344 and 26 genes between tumor and normal parenchyma (PT/NP), tumor thrombus and normal parenchyma (VTT/NP) and tumor thrombus and primary tumor (VTT/PT) respectively. We identified altered key pathways (cytokine activity, regulation of apoptosis, cytoskeleton organization, immune response)._x000D_ 2. We compared these genes with TCGA data and identified 35 genes, which predicted poor outcome. _x000D_ 3. VTT demonstrated statistically significant differential expression of OSM (2.37 fold), INHBA (1.9 fold), CCL2 (2.3 fold), CCL20 (2.9 fold) and IL1B genes (4.5 fold) compared to primary tumor (TT/T), (Figure1). _x000D_ 4. We identified statistically significant higher expression of OSM, INHBA, CCL20, and IL1B genes in higher tumor thrombus level compared to lower tumor thrombus level._x000D_

Conclusions

RNA sequencing of RCC with VTT reveals significant genomic intratumoral heterogeneity. We identified key molecular pathways and differential expression of genes in VTT compared to primary tumor (VTT/PT). Furthermore, these genes were found to be upregulated in higher VTT level compared to lower VTT level. These results will require validation in a larger cohort.

Funding

None