Pd57-02 Creation of a Tissue Expression Biomarker-augmented Prognostic Model for Patients With Metastatic Renal Cell Carcinoma
Year: 2018
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: Prognosis of renal cell carcinoma (RCC) and post-surgical surveillance strategies are based on staging and histology.There are no verified set of molecular biomarkers prognostic of local recurrence to develop individually-tailored clinical management strategies before or after nephrectomy.We measured gene expression profiles of clear cell RCC (ccRCC) to identify biomarkers of ccRCC aggressiveness.METHODS: Clinical information of 361 ccRCC patients, who underwent robotic, laparoscopic or open partial or radical nephrectomy at the University of Arizona College of Medicine/Banner-University Medical Center, Tucson were reviewed, and 33 patients were selected based on staging.TempO-Seq TM (BioSpyder, Carlsbad, CA) was used for whole-transcriptome sequencing of tumor and normal formalinfixed paraffin-embedded (FFPE) tissue from each patient.FFPE was lysed, detector oligos hybridized, ligated, PCR amplified, barcoded, and then samples pooled into a sequencing library.TempO-SeqR was used for alignment and followed by DESeq2 differential expression analysis.RESULTS: The TempO-Seq data grouped 32 out of 33 patients into previously defined molecular subtypes (ccA and ccB).One patient did not fit either subtype.63.6% of patients with higher Stage, Size, Grade, and Necrosis (SSIGN) score (7) were ccB, while 42.9% of patients with low SSIGN score (3) were ccB.The subtype ccB was more common among patients with Fuhrman Grade 3 or 4 (50.0%) and patients with tumor necrosis (60.0%) than patients with Fuhrman Grade 1 or 2 (30.0%) and patients without tumor necrosis (31.3%).Subtype ccB patients also had larger tumor size than subtype ccA patients (mean 7.5 vs. 5.8 cm).ccB patients were significantly older than ccA (P¼0.04).Comparing patients with low vs high SSIGN score identified 590 differentially expressed genes (P ADJ <0.05).Four, including G6PD, were overexpressed in advanced stage and high grade tumors as well as tumors with necrosis (P ADJ <0.05).G6PD had 2.5 fold higher expression in tumors with high compared to low SSIGN score (P ADJ ¼4.4x10 -6 ).CONCLUSIONS: Using an extraction-free assay of FFPE, we identified existing as well as novel gene expression signatures associated with more aggressive ccRCC.Patients with molecular biomarkers of aggressiveness may be counseled towards radical nephrectomy over nephron sparing surgery.
Source: The Journal of Urology
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2795632356