Genetic and Pathway Alterations of Prostate Cancer: In Localized and Metastatic Prostate Cancer

Author:

Yoon Chang Eil1,Kang San1,Rhew Seung ah1,Kwon Hyeok Jae1,Shin Dongho1,Moon Hyong Woo1,Kim Mee Young1,Lee Ji Youl1

Affiliation:

1. The Catholic University of Korea

Abstract

Abstract

Purpose: The purpose of this study was to identify genetic mutations in patients with localized prostate cancer and metastatic prostate cancer and analyze the association between these genes and each patient's clinical course. Materials and Methods: We analyzed 106 patients diagnosed with prostate cancer. Tissue specimens were obtained from prostate biopsy or surgical excision samples and were analyzed by next-generation sequencing at Seoul St. Mary's Hospital between July 1, 2021, and May 31, 2023. We retrospectively evaluated baseline characteristics, including the prostate-specific antigen (PSA) score, tumor, node, metastasis (TNM) staging, Gleason score (GS), and the clinical course, as well as additional treatment and biochemical recurrence (BCR). Results: Of the patients, 65 had localized prostate cancer, and 41 had metastatic prostate cancer. Among baseline characteristics, Significant differences were observed in PSA levels (p = 0.006), T stage distribution (p < 0.001), GS (p < 0.001), and treatment modalities between the two groups. Genetic alterations included single-nucleotide variations (SNVs), copy number variations (CNVs), and structural variations. SNVs in genes like KMT2C, KMT2D, SPOP, and CNVs such as 8p loss and 6q loss were prevalent. Gene fusions like TMPRSS2-ERG and KMT2C-BAGE2 were also observed. Factors such as T stage, GS, and certain genetic mutations were found to be strong predictors in multivariate analysis. Specifically, T stage (p < 0.001), GS (p = 0.048), PIK3CA (p = 0.013), LRP6 (p = 0.012), LRRK2 (p = 0.016), and APOBEC3B deletion (p < 0.001) were confirmed as significant predictors for metastatic prostate cancer while BRCA2 (p < 0.001), BCL6 (p < 0.001), and CHEK2 (p = 0.012) were significant predictors for BCR. Conclusion: The genetic analysis of prostate cancer revealed that mutations like PIK3CA, LRP6, LRRK2, and BRCA2 were associated with metastasis and BCR. Prognosis can be predicted through genetic analysis.

Publisher

Springer Science and Business Media LLC

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