Basic Science: Oncology

Moderated Poster Session

MP1-11 - Gene overexpression in aggressive clear cell renal cell carcinoma identified with whole-transcriptome sequencing and validated against The Cancer Genome Atlas

Thursday, September 20
4:00 PM - 6:00 PM
Location: Room 241

Introduction & Objective : Kidney cancer is one of the 7 most common cancers in the USA.  Currently, primarily staging and histology are used for prognosis and to guide post-surgical surveillance of renal cell carcinoma (RCC). Development of molecular biomarkers of RCC aggressiveness would aid in individually-tailored clinical management strategies before or after nephrectomy.  This study investigated gene expression of clear cell RCC (ccRCC) to identify and validate gene expression signatures that were associated with ccRCC aggressiveness.


Methods : For discovery of gene signatures, 33 patients with ccRCC who underwent partial or radical nephrectomy at University of Arizona College of Medicine were included. Tissues from 1mm punches of formalin-fixed paraffin-embedded samples were used for whole-transcriptome sequencing with a novel ligation-dependent method, TempO-Seq (BioSpyder, Carlsbad, CA).  To validate these findings, The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) mRNA expression data was extracted. Level 3 RNA-Seq Upper Quartile normalized FPKM data and clinical information of 451 patients without previous diagnosis of cancer were included in the analysis.  Statistics performed using Mann-Whitney U test. We considered P <0.05 as significant for validation.


Results : Differential gene expression analysis was performed comparing patients with low Stage, Size, Grade, and Necrosis (SSIGN) score (≤3) to high SSIGN (≥7), and 590 differentially expressed genes were identified with PADJG6PD, APLP1, GCNT3, and PLPP2) were over-expressed in advanced stage (III and IV) and high grade (3 and 4) tumors as well as tumors with necrosis in the discovery dataset.  In the TCGA-KIRC dataset, all four genes were overexpressed in advanced stage compared to early stage ccRCC (PG6PD, APLP1 and GCNT3 were overexpressed in high grade compared to low grade ccRCC (P G6PD, APLP1, and PLPP2 were overexpressed in ccRCC with necrosis (P<0.05).


Conclusions : We identified genes that were overexpressed in ccRCC with high SSIGN scores, and four of them were overexpressed in advanced stage and high grade ccRCC as well as ccRCC with necrosis in discovery and TCGA-KIRC validation dataset.  These genes act as suitable biomarkers of ccRCC aggressiveness with the potential to supplement clinical and surgical management.

Benjamin R. Lee

Professor and Chief, Urology
University of Arizona College of Medicine

Dr. Benjamin Lee, Professor & Chief of Urology at the University of Arizona College of Medicine has focused his career on advancing new treatments for renal cell carcinoma as well as calculus disease, while developing new technologies & techniques for Urologic Oncology & Endourology. He is author or co-author of more than 200 manuscripts, book chapters, videos and abstracts. Dr. Lee graduated from Cornell University magna cum laude. He then attended the Johns Hopkins School of Medicine, and continued his training at the James Buchanan Brady Urological Institute at the Johns Hopkins Hospital. He was Assistant Professor at the North Shore Long Island Jewish Medical Center, and then promoted to Associate Professor. He was promoted to Professor with tenure at the Department of Urology at the Tulane University School of Medicine in 2008, and assumed the position of Professor and Chief of Urology at the University of Arizona College of Medicine in 2016. He has published on methods identifying methods of decreasing recurrence of cancer; explanations why the immune system may be activated differently following laparoscopy compared to open surgery, and has developed nanotechnology applications in urologic disease as well as studies into preserving kidney function during laparoscopic & robotic kidney surgery. Dr. Lee’s research has been recognized by awards from the American Urological Association, The Endourological Society and Urology Journal. He was awarded the prestigious Arthur Smith Award in 2008 for his contributions to the discipline of robotics, laparoscopy, and minimally invasive surgery. He was Organizing Secretary of the 31st World Congress of Endourology which was held in New Orleans, LA in 2013.

Presentation(s):

    Send Email for Benjamin Lee

    Ken Batai

    Division of Urology, University of Arizona College of Medicine

    Presentation(s):

      Send Email for Ken Batai

      Jayce Pangilinan

      Presentation(s):

        Send Email for Jayce Pangilinan

        Michael C. Phung

        Urology Resident
        Division of Urology, University of Arizona College of Medicine

        Presentation(s):

          Send Email for Michael Phung

          Robert Bell

          Pathology Resident
          Department of Pathology, University of Arizona College of Medicine

          Presentation(s):

            Send Email for Robert Bell

            Erika Bracamonte

            Associate Professor, Director of Surgical Pathology
            Department of Pathology, University of Arizona College of Medicine

            Presentation(s):

              Send Email for Erika Bracamonte


              Assets

              MP1-11 - Gene overexpression in aggressive clear cell renal cell carcinoma identified with whole-transcriptome sequencing and validated against The Cancer Genome Atlas



              Attendees who have favorited this

              Please enter your access key

              The asset you are trying to access is locked. Please enter your access key to unlock.

              Send Email for MP1-11 - Gene overexpression in aggressive clear cell renal cell carcinoma identified with whole-transcriptome sequencing and validated against The Cancer Genome Atlas