Genomic Landscape Alterations in Primary Tumor and Matched Lymph Node Metastasis in Hormone-Naïve Prostate Cancer Patients

Abstract

Background: Prostate cancer (PCa) is a disease with a wide range of clinical manifestations. Up to the present date, the genetic understanding of patients with favorable or unfavorable prognosis is gaining interest for giving the appropriate tailored treatment. We aimed 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. Inclusion criteria were patients with lymph node metastasis and patients with PCa with extra capsular extension (pT3) and negative lymph node metastasis. 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 nonsynonym 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%). Conclusion: In the present study we found mostly concordance concerning the ERBB4 mutation between both primary PCa samples and matched lymph node metastasis, underlining that the identification of alterations in the primary tumor is extremely important for cancer prognosis prediction.

Identification and validation of a novel overall survival prediction model for immune-related genes in bone metastases of prostate cancer

“…CD8A (38), FCGR3A (39) and PTPRC (40) are identi ed as candidate biomarkers in various cancers or important molecule in PCa patients with bone metastases. Recent studies have indicated that HRAS alterations in patients with PCa lymph node metastasis demonstrated worse overall survival and disease free survival (41). Further studies are still needed to determine how these hub genes contribute to PCa bone metastases.…”

Prostate Cancer Severity in Relation to Level of Food Processing

“…Several studies have described, through different biochemical pathways, a possible association between metabolic alterations, systemic inflammation related to metabolism, and the incidence of prostate cancer [ 63 , 64 ]. However, other factors involved in prostate cancer development, such as genetics and epigenetics [ 65 , 66 , 67 , 68 ], have been hypothesized to play a role and should be controlled for further. Overall, although the exact mechanism remains to be elucidated, there is a substantial rationale for the association between dietary factors and prostate cancer risk.…”

Identification and validation of a novel overall survival prediction model for immune-related genes in bone metastases of prostate cancer

“…CD8A [38], FCGR3A [39], and PTPRC [40] are identified as candidate biomarkers in various cancers or important molecules in PCa patients with bone metastases. Recent studies have indicated that HRAS alterations in patients with PCa lymph node metastasis demonstrated worse overall survival and disease-free survival [41]. Further studies are still needed to determine how these hub genes contribute to PCa bone metastases.…”