Article ; Online: 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.
BMC cancer
2020 Volume 20, Issue 1, Page(s) 953
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 ... ...
| 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. |
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| MeSH term(s) | Aged ; DNA-Binding Proteins/genetics ; Gene Expression ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/genetics ; Prognosis ; Prostatic Neoplasms/genetics ; Proto-Oncogene Proteins/genetics ; Risk Factors |
| Chemical Substances | DNA-Binding Proteins ; Proto-Oncogene Proteins ; TET2 protein, human (EC 1.13.11.-) |
| Language | English |
| Publishing date | 2020-10-02 |
| Publishing country | England |
| Document type | Journal Article |
| ISSN | 1471-2407 |
| ISSN (online) | 1471-2407 |
| DOI | 10.1186/s12885-020-07438-4 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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