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Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis blockade

We conducted integrated multi-omics evaluation of 823 tumors from advanced renal cell carcinoma (RCC) patients and identified molecular subsets associated with differential clinical outcomes to angiogenesis blockade alone or with a checkpoint inhibitor. Unsupervised transcriptomic analysis revealed six molecular subsets with distinct angiogenesis, immune, cell cycle, metabolism, and stromal programs. While sunitinib was effective in subsets with high angiogenesis, atezolizumab+bevacizumab improved clinical benefit in tumors with high T-effector and/or cell cycle transcription. Somatic mutations in PBRM1 and KDM5C associated with high angiogenesis and AMPK/Fatty acid oxidation gene expression, while CDKN2A/B and TP53 alterations were more prevalent in tumors with increased cell cycle and anabolic metabolism. Sarcomatoid tumors exhibited low prevalence of PBRM1 mutations and angiogenesis markers, frequent CDKN2A/B, BAP1 and TP53 alterations, and increased PD-L1 expression. These findings can be applied to molecularly stratify advanced RCC patients, explain improved outcomes of sarcomatoid tumors to checkpoint blockade, and develop personalized therapies.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006616 1538
EGAD00001006617 1538
EGAD00001006618 1538
EGAD00001006619 Illumina HiSeq 4000 823
Publications Citations
Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade.
Cancer Cell 38: 2020 803-817.e4
A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy.
Genome Med 14: 2022 105
Phagocytosis-Regulators-Based Signature to Predict the Prognosis and Chemotherapy Resistance for Breast Cancer Patients.
Int J Mol Sci 23: 2022 10312
A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategy.
Front Public Health 10: 2022 1029509
A novel immune-related model to predict prognosis and responsiveness to checkpoint and angiogenesis blockade therapy in advanced renal cancer.
Front Oncol 13: 2023 1127448