A novel study led by researchers at Weill Cornell Medicine has provided an extensive analysis of cancer in the ureters or urine-collection cavities of the kidney, known as upper tract urothelial carcinoma (UTUC). Published in Nature Communications, the study offers new insights into the biology of these aggressive cancers and potential ways to treat them.
The researchers analyzed tissue samples from 44 primary and metastatic UTUC tumors, comparing gene mutations and gene activity patterns and mapping cell types using a technology that visualizes protein surface markers at the single-cell resolution. A significant finding was that the basic molecular characteristics of these UTUC tumors, their molecular subtype, remain mostly stable during the evolution from the primary to the metastatic stage. This suggests that oncologists treating UTUC patients may often be able to use analyses of primary tumor samples for molecular subtype-guided treatment of metastases.
UTUC tumors are rare and aggressive, with metastatic tumors being particularly hard to treat. The researchers used DNA and RNA sequencing to map the gene mutations and gene activity patterns in the primary and metastatic samples. They also employed imaging mass cytometry, which labels key surface proteins on individual cells, enabling detailed, cell-by-cell identification and spatial mapping of cell types.
The study confirmed that primary UTUC tumors usually belong to a particular molecular subtype that also features a relative absence of T cells, suggesting immune suppression in the tumor microenvironment. The new analysis found that metastatic UTUC tumors in a given patient tended to have the same characteristics as the primary tumor.
The researchers also observed that metastatic UTUC tumor cells had genetic mutations not found in the primary tumors, with differences being more significant in patients undergoing chemotherapy. These findings set the stage for highly personalized, molecularly-guided primary and metastatic UTUC treatment strategies to improve patient outcomes.