Identification of acetylation-related molecular signatures in knee osteoarthritis patients with significant response to warm-needle acupuncture using machine-learning approaches.

Researchers studied how warm-needle acupuncture (a technique combining acupuncture needles with heat therapy) affects knee osteoarthritis at the molecular level. They collected blood samples from 34 knee osteoarthritis patients before and after treatment, then analyzed changes in genes related to acetylation—a chemical process that affects how genes function in the body.

The study found that warm-needle acupuncture triggered widespread changes in acetylation-related genes, with most of these genes becoming more active after treatment. The researchers identified four specific genes (SPRED1, HDAC3, NSRP1, and DUSP1) that could predict which patients would respond well to the treatment with over 90% accuracy in the study group. They developed a scoring system using these genes that could potentially help determine whether warm-needle acupuncture might work for individual patients.

Interestingly, patients who showed the strongest acetylation activity also had increased immune cell activation, suggesting that warm-needle acupuncture may work partly through immune system regulation. The researchers identified two distinct patient subgroups based on their acetylation patterns, with one group showing higher acetylation activity and more immune cell infiltration.

What this means for patients: This study provides scientific evidence that warm-needle acupuncture creates measurable biological changes in knee osteoarthritis patients. The identified gene markers could eventually lead to personalized treatment approaches, helping predict which patients are most likely to benefit from this therapy before beginning treatment. This could save time and resources by guiding patients toward the most effective therapies for their specific condition. If considering acupuncture for knee osteoarthritis, seek treatment from a licensed acupuncturist with specialized training in warm-needle techniques.

This prospective self-paired study (n=34) utilized transcriptome sequencing to characterize acetylation-related gene expression changes in KOA patients receiving warm-needle acupuncture (WNA). Differential expression analysis revealed global upregulation of acetylation-related genes post-treatment, enriched in protein acetylation and acetyltransferase pathways. Machine learning feature selection (LASSO and SVM-RFE) identified four key genes (SPRED1, HDAC3, NSRP1, DUSP1) that demonstrated robust predictive performance via a multigene logistic regression model (AUC=0.908 training set; 0.810 validation set). Consensus clustering revealed two acetylation subtypes with distinct immune profiles; subtype B exhibited higher acetylation activity and immune-cell infiltration per ssGSEA and infiltration profiling. Co-expression network analysis identified 107 highly co-regulated genes clustering congruently with subtype classification. Clinical implications: WNA substantially remodels the peripheral acetylation-related transcriptomic landscape in KOA, with enhanced acetylation activity correlating with immune activation. The four-gene nomogram offers potential for individualized WNA efficacy prediction and mechanistic understanding of acupuncture's immunomodulatory effects in osteoarthritis management.