Effects of tai chi qigong on gene expression profiles in older male cancer survivors with fatigue.

12038 Background: The HERO trial showed that Tai Chi Qigong (TCQ) reduced fatigue (primary endpoint) in male cancer survivors. Fatigue-related biological pathways influenced by mind-body therapies, such as TCQ, remain poorly defined. This trial hypothesized that TCQ, compared to an exercise-intensity matched (EIM) intervention and usual care (UC), would have a more favorable effect on the regulation of two major fatigue-associated functional gene clusters: a) inflammation-vasodilation-metabolite sensing and b) energy and adrenergic activation among older male cancer survivors with fatigue. Methods: In this three-arm randomized trial (NCT 03345563), 113 male cancer survivors aged ≥ 55 years with fatigue were randomized to 12 weeks of TCQ (n = 45), EIM (n = 43), or UC (n = 25), delivered twice weekly with recommended home practice. Gene expression profiles were assessed at baseline and at 1 week and 3 months post-intervention using genome-wide transcriptional profiling of blood samples. A key secondary endpoint was changes in gene expression at the 3-month follow-up. A minimum of 8 subjects per study arm is required to achieve 80% power (two-sided alpha = 0.05) to detect a 2.0-fold change in gene expression. Intervention effects were evaluated using an intention-to-treat approach and general mixed linear models, with baseline adjustment and time of sample collection included as time-varying covariates. Multiple comparisons were controlled for using the false discovery rate (FDR). Upregulation of DBI, IL-10, ADRB2, VIPR2, OXTR, ASIC3, P2RX4, P2RX7, ATP5E, NDUFS5 genes and downregulation of TNF, NR3C1, P2RY1, HSPA2 genes were deemed as favorable effects. Mean difference (MD), 95% CI, and FDR corrected p-values were reported. Results: TCQ favorably regulated the expression of genes associated with inflammation (TNF: MD = -1.25; CI: -1.97 – -0.53; p = 0.001 and IL-10: MD = 0.51; CI: 0.02 – 1.00; p = 0.043), metabolite-sensing (P2RX4: MD = 0.45; CI: 0.04 – 0.85; p = 0.032), and energy activation (P2RY1: MD = -0.43; CI: -0.95 – -0.08; p = 0.037, ATP5E: MD = 0.15; CI: 0.05 – 0.30; p = 0.035, and NDUFS5: MD = 0.14; CI: 0.02 – 0.28; p = 0.042) at 3 months post-intervention. EIM favorably regulated genes associated with vasodilation (OXTR: MD = 0.89; CI: 0.36 – 1.42; p = 0.001) and inflammation (NR3C1: MD = -0.24; CI: -0.47 – -0.01; p = 0.043). Compared with EIM, TCQ produced greater increases in ADRB2, an adrenergic activator (MD:0.81; CI: 0.26 – 1.35; p = 0.003) and P2RX4 (MD:0.56; CI: 0.12 – 1.01; p = 0.013) and favorably decreased the expression of P2RY1 (MD:-0.93; CI: -1.51 – -0.35; p = 0.002). Conclusions: TCQ produced meaningful changes in inflammatory, adrenergic, energy, and metabolic pathways, supporting potential biological mechanisms through which TCQ may reduce fatigue in older male cancer survivors. Larger trials with a broader representation of participants are needed to confirm these pathway-level effects. Clinical trial information: NCT03345563 .