Characterization of FOLH1 Expression in Renal Cell Carcinoma

Transcript:

Rana McKay:     

Hi, my name is Rana McKay. I'm a genitourinary medical oncologist at the University of California in San Diego, where I lead our genitourinary medical oncology team.
 

Certainly. The FOLH1 gene encodes for prostate-specific membrane antigen. This is a transmembrane glycoprotein that's highly expressed in the prostate cancer cells, and actually it's also present on endothelial cells in the neovasculature of several solid tumors including renal cell carcinoma. There've been emerging reports of improved staging in RCC using PSMA PET compared to conventional imaging. Also now, there are PSMA-targeted radioligand therapies and other therapies that are being investigated.

So determining FOLH1 and PSMA expression levels in RCC could therefore have diagnostic and potentially therapeutic implications, which is why we embarked on our study.

The primary objective of our study was to evaluate the expression of the FOLH1 gene in renal cell carcinoma and secondary objective included to evaluate FOLH1 gene expression between clear cell and non-clear cell histologies, to evaluate co-occurring DNA alterations and also look at transcriptomic RNA signatures, specifically the angiogenic high signatures that have been previously described. We also sought to evaluate efficacy of VEGF inhibition in tumors classified as FOLH1 high and low.

We utilized NextGen sequencing of DNA and RNA, which was performed on renal cell carcinoma patient specimens. We had over 1,700 specimens that were utilized for this analysis, and we were able to characterize FOLH1 expression within this cohort.

With regards to our findings, FOLH1 expression was similar between patients of different sexes, and also there was no difference in age between the FOLH1 high and low groups. FOLH1 expression was significantly higher in patients with clear cell RCC compared to those with non-clear cell histologies. The FOLH1 expression did vary by specimen site in reference to the kidney. So when we looked at the lymph node, bone, liver, and most notably, there was significantly lower FOLH1 expression in lymph nodes compared to the kidney. FOLH1 expression was strongly correlated with an angiogenic gene signature compared to T-effector and myeloid signatures. We also observed there was kind of a enrichment of endothelial cells in tumors that had high FOLH1 expression, as we would suspect.

With regards to overall survival and time on systemic therapy, we did find that FOLH1 expression was associated with a longer time on treatment for patients receiving cabozantinib compared to the FOLH1 low group.

Conclusion. We observed differential patterns of FOLH1 expression by histology and tumor site in this analysis. FOLH1 expression correlated with angiogenic gene expression score, and there was distinct differences in the TME composition, with an endothelial cell predominance in FOLH1 high tumors. There also seemed to be a positive correlation with response to anti-angiogenic treatment. So I think these data are quite provocative because I think it potentially opens up the door to investigate FOLH1 and PSMA-targeted diagnostic and therapeutic strategies in RCC.