Whole transcriptome sequencing was performed for clear cell RCC patient samples submitted to a commercial CLIA-certified laboratory (Caris Life Sciences, Phoenix, Arizona) from February 2019 to September 2020. Tumor gene expression profiling and hierarchical clustering based on the validated 66-gene signature were used to identify patient subgroups. Samples from both primary tumors and metastatic sites were included.
There was a total of 316 patients with clear cell RCC, with a median age of 62 (range 32-90) years, of which 71.8% were men that were included in this study. Tissue samples were obtained from the primary tumor (46.5%), lung (12.3%), bone (9.5%), liver (4.7%), and other metastatic sites (27%). Gene expression analysis identified angiogenic subgroups in 24.1% of patients, mixed in 51.3%, and T-effector subgroups in 24.7%. As follows is the hierarchical clustering of gene expression signature:
Patients with angiogenic subgroup tumors compared to those with T-effector subgroup tumors were more likely to be older (63 versus 60 years, p=0.035), female (40.8% versus 16.7%, p=0.0009), and more frequently found in pancreatic/small bowel metastases (75% versus 12.5%, p=0.0103). Biomarkers of potential response to immunotherapy such as PD-L1 (p=0.0021), tumor mutational burden (not significant), and dMMR/MSI-H status (not significant) were more frequent in the T-effector subgroup PBRM1 mutations were more common in the angiogenic subgroup (62.0% vs 37.5%, p=0.0034) while BAP1 mutations were more common in the T-effector subgroup (18.6% versus 3.0%, p= 0.0035). Immune cell population abundance (ie. NK cells, monocytes) and immune checkpoint gene expression (TIM-3, PD-L1, PD-L2, CTLA4) were also increased in the T-effector subgroup.
Dr. Barata concluded with the following summary points from his presentation:
- These hierarchical clustering results based on the 66-gene expression signature were concordant with results from prior studies
- Angiogenic tumors were more likely to be found in patients who were older or female, and were more likely to harbor gastrointestinal metastases, stromal cell population, and PBRM1 mutations
- BAP1 mutations and immunotherapy markers such as tumor mutational burden and dMMR/MSI-H, PD-L1, and immune cell population were more frequent in the “T-effector” signature
- These findings have potential predictive value and require further validation in prospective clinical trials
Presented by: Pedro C. Barata, MD, MSc, Assistant Professor of Medicine Hematology & Medical Oncology, Tulane University School of Medicine, New Orleans, Louisiana
Written by: Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
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