ArticleAnnals of surgical oncology2026
Cyclic GMP-AMP Synthase Expression in Hepatocellular Carcinoma: A Double-Edged Biomarker for Prognosis and Immunotherapy Response.
Article in Annals of surgical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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Corrections and comments
- Erratum issued
Authors and funding
15 authors.
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Abstract
backgroundHepatocellular carcinoma (HCC) remains a leading cause of cancer mortality. Although atezolizumab plus bevacizumab (ATZ/BEV) is the standard therapy, only a subset of patients achieves durable responses. Cyclic GMP-AMP synthase (cGAS) regulates innate immunity, but its clinical role in HCC is unclear. PATIENTS AND
methodsPatients with primary HCC were retrospectively analyzed and divided into cohort 1 (353 patients who underwent hepatectomy without prior therapy) and cohort 2 (42 patients who received ATZ/BEV after recurrence). In cohort 1, cGAS expression was quantified by immunohistochemistry and analyzed for correlations with clinicopathological features, disease-free survival (DFS), overall survival (OS), and independent prognostic factors. In cohort 2, cGAS was assessed for associations with progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).
resultsIn cohort 1, 25.4% of patients had high cGAS expression (immunohistochemistry score ≥ 3). Although cGAS expression was unrelated to clinicopathological factors, it was associated with shorter DFS (2.37 versus 3.72 years; p = 0.019) and OS (6.19 years versus not reached; p = 0.002). Multivariate analysis identified cGAS positivity as an independent predictor of poor prognosis. Conversely, in cohort 2, high cGAS expression correlated with longer PFS after ATZ/BEV (12.6 versus 6.5 months; p = 0.020) and higher ORR (43.8% versus 11.5%; p = 0.0173) and DCR (93.8% versus 65.4%; p = 0.0361).
conclusionscGAS functions as a dual biomarker, predicting poor prognosis after hepatectomy but favorable response to immunotherapy. These findings underscore the clinical relevance of cGAS and its potential to guide personalized HCC treatment.
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