1. Renal cell carcinoma histologic subtypes exhibit distinct transcriptional profiles.
- Author
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Barata, Pedro, Gulati, Shuchi, Elliott, Andrew, Hammers, Hans, Burgess, Earle, Gartrell, Benjamin, Darabi, Sourat, Bilen, Mehmet, Basu, Arnab, Geynisman, Daniel, Dawson, Nancy, Zibelman, Matthew, Zhang, Tian, Wei, Shuanzeng, Ryan, Charles, Heath, Elisabeth, Poorman, Kelsey, Nabhan, Chadi, and McKay, Rana
- Subjects
Cancer ,Genetics ,Molecular genetics ,Oncology ,Urology ,Humans ,Carcinoma ,Renal Cell ,Kidney Neoplasms ,Transcriptome ,Female ,Male ,Gene Expression Regulation ,Neoplastic ,Middle Aged ,Aged ,Neoplasm Proteins ,Gene Expression Profiling - Abstract
Molecular profiling of clear cell renal cell carcinoma (ccRCC) tumors of patients in a clinical trial has identified distinct transcriptomic signatures with predictive value, yet data in non-clear cell variants (nccRCC) are lacking. We examined the transcriptional profiles of RCC tumors representing key molecular pathways, from a multi-institutional, real-world patient cohort, including ccRCC and centrally reviewed nccRCC samples. ccRCC had increased angiogenesis signature scores compared with the heterogeneous group of nccRCC tumors, while cell cycle, fatty acid oxidation/AMPK signaling, and fatty acid synthesis/pentose phosphate signature scores were increased in one or more nccRCC subtypes. Among both ccRCC and nccRCC tumors, T effector scores statistically correlated with increased immune cell infiltration and were more commonly associated with immunotherapy-related markers (PD-L1+/TMBhi/MSIhi). In conclusion, this study provides evidence of differential gene transcriptional profiles among ccRCC versus nccRCC tumors, providing insights for optimizing personalized and histology-specific therapeutic strategies for patients with advanced RCC.
- Published
- 2024