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Cancer, Stress, Anesthesia, and Immune Response / Immune Cells in Cancer · Journal article
Journal of Proteome Research · August 10, 2026
Early or partial results. Treat as a signal, not a conclusion.
This pilot study identified a five-protein serum signature (TGF-α, EN-RAGE, CASP-8, ST1A1, IL-10RA) that discriminated opioid responders from nonresponders with AUC 0.902, and documented proteomic changes after opioid initiation in 44 cancer pain patients. The findings are exploratory and hypothesis-generating; the nomogram and protein associations require prospective validation in independent cohorts before clinical application.
Pilot cross-sectional and longitudinal proteomics study. Cancer pain patients initiating opioid therapy; eligibility criteria not specified in abstract.. Intervention: Opioid initiation for cancer pain.. Compared with: Responders versus nonresponders to opioid therapy (no external control arm).. n = 44. Not stated..
Five-protein nomogram predicted opioid efficacy with AUC 0.902, substantially outperforming CRP (AUC 0.625) Nine proteins were differentially expressed between responders and nonresponders in cross-sectional analysis Longitudinal analysis showed upregulation of β-NGF, MCP-4, IL-1alpha, and IL-13 and downregulation of CD6, IL-12beta, and SCF after opioid treatment
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These proteomic findings suggest potential biomarkers for predicting opioid efficacy and understanding treatment-induced immune changes, but the results are exploratory and cannot yet inform clinical decision-making without prospective validation and independent replication in a larger cohort.
This is a small pilot cross-sectional and longitudinal study with a single-arm design and no randomized control, identifying protein signatures and post-hoc mechanistic associations that require confirmatory evidence in an independent cohort.
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Quoted from the source exactly as published.
These proteomic findings suggest potential biomarkers for predicting opioid efficacy and understanding treatment-induced immune changes, but the results are exploratory and cannot yet inform clinical decision-making without prospective validation and independent replication in a larger cohort.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Abstract Opioid analgesia shows substantial interindividual variability in cancer patients, yet the underlying serum inflammatory alterations remain poorly characterized. This study collected plasma samples from 44 cancer pain patients before and after opioid initiation, quantifying 92 immunoinflammation proteins by Olink proteomics. Cross-sectional analysis identified nine differentially expressed proteins between responders and nonresponders. A five-protein nomogram involving TGF-α, EN-RAGE, CASP-8, ST1A1, and IL-10RA demonstrated superior predictive performance for opioid efficacy (AUC 0.902) compared to traditional CRP (AUC 0.625). Longitudinal analysis of this population revealed upregulation of β-NGF, MCP-4, IL-1alpha, and IL-13, and downregulation of CD6, IL-12beta, and SCF after treatment. STRING analysis clustered these proteins into three functional groups: efficacy-related (NGF), bowel-inflammation-related (IL-12/IL-13), and CD6-related. Notably, expression of IL-12β showed a significant efficacy–constipation interaction: constipation completely reversed the efficacy-IL-12 association, and higher IL-12 levels predicted favorable response only in nonconstipated patients. These findings established a pretreatment protein signature for predicting opioid efficacy and revealed systemic immune reprogramming following opioid therapy.
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