Genomic landscape alterations in primary tumor and matched lymph node metastasis in prostate cancer patients

Abstract

Abstract Background: Prostate cancer (PCa) is a disease with a wide range of clinical manifestations. Up to date, the genetic understanding of patients with favorable or unfavorable prognosis is gaining interest in order to give the appropriate tailored treatment. The aim of the present study was to investigate genetic changes associated with lymph node metastasis in a cohort of hormone-naïve Pca patients. Methods: We retrospectively analyzed data from 470 patients who underwent surgery for PCa between 2010 and 2020 at the Department of Urology, University of Catania. The final cohort consisted of 17 different patients (11 PCa with lymph node metastasis and 6 PCa without lymph node metastasis). Through the cBioPortal online tool, we analyzed gene alterations and their correlations with clinical factors. Results: A total of 688 Intronic, Synonym and Non-Synonym mutations were sequenced. The gene with the most sequenced mutations was ERBB4 (83 mutations, 12% of 688 total) while the ones with the lower percentage of mutations were AKT1, FGFR2 and MLH1 (1 mutation alone, 0.14% of 688 total). We used the cBioPortal online tool to study the alterations of the genes ERBB4, HRAS, KIT, ABL1, CTNNB1 and their correlation with prognosis using a total of 23 studies (9377 samples). When incorporating KIT, HRAS and CTNNB1 alterations in combination score we found that overall survival was statistically worse (p<0.01) and also disease-free survival (p=0.02) compared to unaltered group. Conclusion: In the present study we found mostly concordance between both primary PCa samples and matched lymph node metastasis in terms of genomic alterations, underlining that alterations in primary tumor are extremely important for cancer prognosis prediction. We demonstrated worse overall survival and disease-free survival in patients with combined alteration of KIT, HRAS and CTNNB1. These results can be applied for monitoring disease and drug response after curative treatment.