Gene Expression Difference Between Primary and Metastatic Renal Cell Carcinoma Using Patient-Derived Xenografts

Metastasis is the leading cause of cancer-related death. A small proportion of tumor cells can spread to other tissues through the lymph system or bloodstream and colonize in a new microenvironment. However, not all tumors from the primary site can metastasize. What is the difference between metastatic and primary tumors? Can such difference be preserved in widely used patient-derived xenografts (PDX)? To answer these questions, we analyzed the single-cell gene expression profiles of 36 cells from PDX of metastatic renal cell carcinoma (mRCC), 47 cells from PDX of primary RCC (pRCC), and 35 cells from parental mRCC (pt-mRCC). First, the gene expression patterns of PDX-mRCC and PDX-pRCC were compared, and the PDX-mRCC signatures were generated. Such signatures reflected the difference between metastatic and primary tumors. Second, the pt-mRCC were tested on whether they can be correctly classified into the PDX-mRCC class rather than PDX-pRCC. We found that pt-mRCC were very similar with PDX-mRCC. Our results prove that the PDX is a great research model for metastatic tumors since it preserved the essences for tumor metastasis. Our results justify the applications of PDX in metastatic tumor studies.