mRNA expression, tumor heterogeneity, and response to therapy in patients with advanced renal cell carcinoma treated with immune-based combinations (ARON-1α).

BACKGROUND

Renal Cell Carcinoma (RCC) represents a spectrum of tumors, characterized by heterogeneous growth patterns, histology and response to immune-based combinations.

OBJECTIVES

The aim of the present retrospective analysis was to investigate the mRNA expression of 32 genes associated with RCC carcinogenesis and their potential involvement in patients treated with first-line immune-based combination therapies. Additionally, we examined the role of tumor heterogeneity by comparing mRNA expression levels between primary renal tumors and metastatic sites in a group of patients included in the ARON-1 study.

PATIENTS AND METHODS

The study included patients with advanced RCC treated with first-line immune-based therapies. Total RNA was extracted from fixed paraffin-embedded tissue slices using the RNeasy FFPE Mini Kit. Quantitative RT-PCR was performed using the IQ5 Multicolor real-time PCR detection system. Coefficient of variations were calculated for each gene and compared between primary and metastatic samples.

RESULTS

17 patients were included in this analysis; 9 of them had both primary and metastatic samples available. Three of the 4 patients showing the highest mRNA expression levels of the 32 analyzed genes reported complete remissions, while 2 of the 3 patients with the lowest expression levels were primary refractory to first-line therapy. As for tumor heterogeneity, was the only gene significantly deregulated in the paired comparison.

CONCLUSIONS

We showed differences in mRNA expression between primary and metastatic sites, and proposed a possible link to the response to first-line immune combination therapies. Additional research is required to clarify their potential as prognostic or predictive biomarkers.