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A 38-gene model comprised of key TET2-associated genes shows additive utility to high-risk prostate cancer cases in the prognostication of biochemical recurrence.

Abstract：

BACKGROUND:Early treatment of patients at risk for developing aggressive prostate cancer is able to delay metastasis and reduce mortality; as such, up-front identification of these patients is critical. Several risk classification systems, including CAPRA-S, are currently used for disease prognostication. However, high-risk patients identified by these systems can still exhibit wide-ranging disease outcomes, leading to overtreatment of some patients in this group. METHODS:The master methylation regulator TET2 is downregulated in prostate cancer, where its loss is linked to aggressive disease and poor outcome. Using a random forest strategy, we developed a model based on the expression of 38 genes associated with TET2 utilizing 100 radical prostatectomy samples (training cohort) with a 49% biochemical recurrence rate. This 38-gene model was comprised of both upregulated and downregulated TET2-associated genes with a binary outcome, and was further assessed in an independent validation (n = 423) dataset for association with biochemical recurrence. RESULTS:38-gene model status was able to correctly identify patients exhibiting recurrence with 81.4% sensitivity in the validation cohort, and added significant prognostic utility to the high-risk CAPRA-S classification group. Patients considered high-risk by CAPRA-S with negative 38-gene model status exhibited no statistically significant difference in time to recurrence from low-risk CAPRA-S patients, indicating that the expression of TET2-associated genes is able to separate truly high-risk cases from those which have a more benign disease course. CONCLUSIONS:The 38-gene model may hold potential in determining which patients would truly benefit from aggressive treatment course, demonstrating a novel role for genes linked to TET2 in the prognostication of PCa and indicating the importance of TET2 dysregulation among high-risk patient groups.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Kamdar S,Fleshner NE,Bapat B

doi

10.1186/s12885-020-07438-4

subject

Has Abstract

pub_date

2020-10-02 00:00:00

pages

953

issue

issn

1471-2407

pii

10.1186/s12885-020-07438-4

journal_volume

pub_type

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A 38-gene model comprised of key TET2-associated genes shows additive utility to high-risk prostate cancer cases in the prognostication of biochemical recurrence.