IKCS 2021: Gene Expression Profiling (GEP) of Non-Clear Cell Renal Cell Carcinoma

(UroToday.com) In the Top Abstracts session of the 2021 International Kidney Cancer Symposium (IKCS): North America meeting, Dr. Barata presented their work examining gene expression profiling (GEP) in non-clear cell renal cell carcinoma.

He began by highlighting that, while we have seen the emergence of many active treatment options in advanced renal cell carcinoma (RCC), there is a distinct lack of predictive biomarkers to guide treatment choice. Gene expression signatures, including anti-angiogenic and immune signatures, have been derived from IMmotion151 and JAVELIN Renal 101. These have focused on patients with clear cell RCC. Thus, they now were interested in focusing on patients with non-clear cell histology.

They employed DNA/RNA next-generation sequencing of tumor samples from the Caris Life Sciences lab. They defined molecular subgroups according to the criteria set out by Motzer et al. and examined 7 clusters.

The authors examined 657 RCC patient samples, including patients with papillary disease (9.6%), chromophobe (4.6%), medullary (1.2%), collecting duct (0.95), and mixed (6.2%) subtypes. Approximately half of samples (51.7%) were derived from the kidney while the remainder were from a variety of metastatic sites. Patients with clear cell RCC were included as a comparator.

While most patients with ccRCC had angiogenic or angio/stromal signatures (in keeping with prior work), there was a predominance of the proliferative cluster and lack of angiogenic cluster among patients with non-clear cell subtypes.

Using a heatmap, sorted by signature type, he noted that sarcomatoid/rhabdoid features were associated with T-effector/proliferative and stromal/proliferative subtypes. Notably, while the signatures differed between patients with ccRCC and nccRCC histology as highlighted above, among those with sarcomatoid/rhabdoid features, there was relatively consistent enrichment of the proliferative subgroup.

Unfortunately, this dataset is limited by a lack of clinical nuance. However, these data show a strong association between nccRCC and the proliferative subtype. Further prospective validation is required to move this forward to a new understanding of personalized treatment of patients with these tumors.