Scholarlink

Background <p>Hepatocellular 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.</p> Patients and Methods <p>Patients 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).</p> Results <p>In 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; <i>p</i> = 0.019) and OS (6.19 years versus not reached; <i>p</i> = 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; <i>p</i> = 0.020) and higher ORR (43.8% versus 11.5%; <i>p</i> = 0.0173) and DCR (93.8% versus 65.4%; <i>p</i> = 0.0361).</p> Conclusions <p>cGAS 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Cyclic GMP–AMP Synthase Expression in Hepatocellular Carcinoma: A Double-Edged Biomarker for Prognosis and Immunotherapy Response

  • 期刊论文

  • 发表日期：

    2026年1月16日

查看全文
  • Hitoshi Iwasaki,
  • Shinji Itoh,
  • Yuki Nakayama,
  • Katsuya Toshida,
  • Takuma Ishikawa,
  • Junya Mita,
  • Yu Mingyang,
  • Norifumi Iseda,
  • Kyohei Yugawa,
  • Shohei Yoshiya,
  • Takashi Motomura,
  • Takeo Toshima,
  • Shinichi Aishima,
  • Yoshinao Oda,
  • Tomoharu Yoshizumi

摘要

Background

Hepatocellular 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 Methods

Patients 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).

Results

In 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).

Conclusions

cGAS 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.