Analysis Maps Evolution of UTUC Cells

The molecular characteristics of primary and metastatic tumors in patients with upper tract urothelial carcinoma (UTUC) are mostly stable, suggesting that oncologists may be able to use analyses of primary tumor samples for molecular subtype-guided treatment of metastases, according to a research team from Weill Cornell Medicine, New York, New York.

The team published their findings online in Nature Communications.

“Frequently, we are unable to obtain sufficient biopsy tissue from metastatic tumors and have to rely on the molecular analysis of the primary tumor, so it’s important to know that the molecular subtype based on RNA expression is generally stable from the primary to the metastatic stages,” said Bishoy Faltas, MD, an assistant professor of medicine at Weill Cornell Medicine, who co-led the study with colleague Juan Miguel Mosquera, MD, a professor of pathology and laboratory medicine.

To better understand genomic and transcriptomic differences between primary and metastatic UTUC, researchers examined tissue samples from 44 tumors from 28 patients. They used DNA and RNA sequencing to map the gene mutations and gene activity patterns in the tumors and used a newer technique called Imaging Mass Cytometry to label key surface proteins on individual cells in the samples. The technique allowed for detailed, cell-by-cell identification and spatial mapping of cell types.

“We were able to understand the contributions of different cell types to these molecular subtypes and how they evolve over the cancer’s natural history by analyzing the protein expression of hundreds of thousands of single cells from these tumors,” Dr Faltas explained.

The study also identified genetic mutations in metastatic tumor cells not found in primary tumors. Because the differences were significantly greater in patients undergoing chemotherapy, researchers suspect the treatment may have induced some of the mutations.

In addition to promoting personalized, molecularly-guided treatment strategies for patients, the findings provide insights that could accelerate the development of targeted therapies and immunomodulatory treatment approaches for patients with UTUC, according to the research team. 

“This dataset we generated provides unique insights into UTUC biology and should be an important resource for researchers and clinicians,” said Dr Mosquera, who also serves as director of research pathology in the institute for precision medicine.

Reference

1. Ohara K, Rendeiro AF, Bhinder B, et al. The evolution of metastatic upper tract urothelial carcinoma through genomic-transcriptomic and single-cell protein markers analysis. Nat Commun. 2024;15(1):2009. doi:10.1038/s41467-024-46320-w
2. Mapping the evolution of urinary tract cancer cells. News release. Weill Cornell Medicine; March 18, 2024. Accessed October 14, 2024.