Tissue-specific Biological Aging Predicts Progression in Prostate Cancer and Acute Myeloid Leukemia

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Sep 25

PMID 37746266

Authors

Anitha Ramakrishnan

Indrani Datta

Sukanya Panja

Harmony Patel

Yingci Liu

Michael W Craige

Cassandra Chu

Giselle Jean-Marie

Abdur-Rahman Oladoja

Isaac Kim

Antonina Mitrofanova

Affiliations

Soon will be listed here.

Abstract

Introduction: Chronological aging is a well-recognized diagnostic and prognostic factor in multiple cancer types, yet the role of biological aging in manifesting cancer progression has not been fully explored yet.

Methods: Given the central role of chronological aging in prostate cancer and AML incidence, here we investigate a tissue-specific role of biological aging in prostate cancer and AML progression. We have employed Cox proportional hazards modeling to associate biological aging genes with cancer progression for patients from specific chronological aging groups and for patients with differences in initial cancer aggressiveness.

Results: Our prostate cancer-specific investigations nominated four biological aging genes (CD44, GADD45B, STAT3, GFAP) significantly associated with time to disease progression in prostate cancer in Taylor et al. patient cohort. Stratified survival analysis on Taylor dataset and validation on an independent TCGA and DKFZ PRAD patient cohorts demonstrated ability of these genes to predict prostate cancer progression, especially for patients with higher Gleason score and for patients younger than 60 years of age. We have further tested the generalizability of our approach and applied it to acute myeloid leukemia (AML). Our analysis nominated three AML-specific biological aging genes (CDC42EP2, CDC42, ALOX15B) significantly associated with time to AML overall survival, especially for patients with favorable cytogenetic risk score and for patients older than 56 years of age.

Discussion: Comparison of the identified PC and AML markers to genes selected at random and to known markers of progression demonstrated robustness of our results and nominated the identified biological aging genes as valuable markers of prostate cancer and AML progression, opening new avenues for personalized therapeutic management and potential novel treatment investigations.

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