High ATM Expression Linked to Worse Outcomes in Patients With Prostate Cancer

Using transcriptomic analysis, researchers observed that patients with prostate cancer with high ataxia telangiectasia mutated (ATM) expression have worse outcomes and a higher risk of metastasis. The results of their study were presented at the 2022 American Society for Radiation Oncology Annual Meeting.

While the prognostic and therapeutic value of ATM somatic and germline alterations have been characterized in prostate cancer, ATM expression in the context of radiotherapy (RT) for localized prostate cancer is less understood.

In this study, presenting author Karthik Palaniappan Meiyappan, BS, and colleagues used whole transcriptome assays to assess 5780 radical prostatectomy (RP) samples for ATM expression. The investigators also analyzed 245 patients who had undergone either adjuvant or salvage RT after RP. Subsequently, ATM expression was assessed in relation to RT response using a 1:1 matched cohort (n=98 treated with RT, n=98 with no RT). The researchers also explored the association between ATM expression and more than 200 genomic signatures, biological pathways, and a Genomic Classifier (GC). ATM expression was assessed for metastasis-free survival (MFS), which was the key end point of interest.

According to the results, ATM was markedly overexpressed in high GC patients, which, the researchers noted, is a molecular surrogate for poor outcomes. High ATM expression was linked with worse MFS (hazard ratio [HR], 1.16; 95% CI, 1.51-1.96; P=.002). The researchers observed that in patients treated with RT, high ATM was correlated with worse MFS juxtaposed to lower ATM (10-year MFS 30% vs 61%), whereas in the patients treated without RT, high ATM was not significantly associated with worse MFS.

“Prostate cancer patients harboring high ATM expression by transcriptomic analysis had poorer outcomes with a significantly higher risk of metastasis. Given the worse outcomes, particularly in patients treated with RT, a high ATM expression may be a marker of resistance to DNA-damaging agents,” the researchers concluded.

Source: Meiyappan KP, Alshalalfa M, Dee EC, et al. Transcriptomic analysis of ATM expression in localized prostate cancer – implications for radiotherapy treatment. Abstract 299. Presented at the 2022 ASTRO Annual Meeting; October 23-26, 2022; San Antonio, TX.