Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia

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

doi:10.3389/fonc.2023.1222168

Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia

Front Oncol. 2023 Sep 6:13:1222168. doi: 10.3389/fonc.2023.1222168. eCollection 2023.

Authors

Anitha Ramakrishnan¹, Indrani Datta¹, Sukanya Panja¹, Harmony Patel^{1

2}, Yingci Liu^{1

3}, Michael W Craige¹, Cassandra Chu¹, Giselle Jean-Marie^{1

4}, Abdur-Rahman Oladoja^{1

4}, Isaac Kim⁵, Antonina Mitrofanova^{1

6}

Affiliations

¹ Department of Biomedical and Health Informatics, School of Health Professions, Rutgers, The State University of New Jersey, Newark, NJ, United States.
² Department of Health Informatics and Information Management, College of Applied and Natural Sciences, Louisiana Tech University, Ruston, LA, United States.
³ New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, United States.
⁴ Rutgers Youth Enjoy Science Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States.
⁵ Department of Urology, Yale School of Medicine, New Haven, CT, United States.
⁶ Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States.

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.

Keywords: biological aging; biomarkers; cancer progression; genome-wide analysis; precision medicine.

Grants and funding

AM is supported by R01LM013236-01, ACS RSG-21-023-01-TBG, the American Cancer Society (ACS) Research Scholar Award, and the NJCCR COCR21RBG00 grant. MC is supported by the National Science Foundation under Grant No. 2127309 to the Computing Research Association for the CIFellows Project. GJ-M and A-RO were supported by the Rutgers Youth Enjoy Science Program (RUYES) through the National Institutes of Health (NIH) Grant No. NCI 1R25CA247785.