Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Br J Cancer. 2023 Jun;128(11):2081-2088. doi: 10.1038/s41416-023-02223-z. Epub 2023 Mar 28.
The majority of hepatocellular carcinoma (HCC) cases occur in the presence of cirrhosis. Biomarkers of cirrhosis-associated immune dysfunction such as CD8+ T cell cytokines could aid HCC risk assessment.
CD8+ T cell cytokines were determined in pre-diagnostic serum in two studies including 315 HCC case-control pairs in the Shanghai Cohort Study (SCS) and 197 pairs in the Singapore Chinese Health Study (SCHS). Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for HCC with levels of five cytokines-soluble CD137 (sCD137), soluble Fas (sFas), perforin, macrophage inflammatory protein 1-beta (MIP-1β), and tumour necrosis factor alpha (TNF-α).
sCD137 levels were significantly higher in HCC cases than controls in both cohorts (Ps < 0.001). Compared with the lowest quartile, multivariable-adjusted ORs (95% CI) of HCC for the highest sCD137 quartile were 3.79 (1.73, 8.30) in the SCS and 3.49 (1.44, 8.48) in the SCHS. The sCD137-HCC association was independent of hepatitis B seropositivity and follow-up time. No other cytokine was consistently associated with HCC risk.
sCD137 was associated with higher risk of HCC in two studies nested in general population cohorts. sCD137 may be a long-term risk marker of HCC development.
大多数肝细胞癌 (HCC) 病例发生在肝硬化存在的情况下。与肝硬化相关的免疫功能障碍的生物标志物，如 CD8+ T 细胞细胞因子，可辅助 HCC 风险评估。
在两项研究中，包括上海队列研究 (SCS) 中的 315 例 HCC 病例对照对和新加坡华人健康研究 (SCHS) 中的 197 对，在预诊断血清中测定了 CD8+ T 细胞细胞因子。条件逻辑回归用于估计五种细胞因子（可溶性 CD137（sCD137）、可溶性 Fas（sFas）、穿孔素、巨噬细胞炎症蛋白 1-β（MIP-1β）和肿瘤坏死因子-α（TNF-α））与 HCC 的比值比 (OR) 和 95%置信区间 (CI)。
在两个队列中，sCD137 水平在 HCC 病例中均明显高于对照组（均 P<0.001）。与最低四分位数相比，sCD137 最高四分位数的 HCC 多变量调整 OR（95%CI）在 SCS 中为 3.79（1.73，8.30），在 SCHS 中为 3.49（1.44，8.48）。sCD137 与 HCC 的关联独立于乙型肝炎血清阳性和随访时间。没有其他细胞因子与 HCC 风险一致相关。
在两项嵌套于一般人群队列的研究中，sCD137 与 HCC 风险增加相关。sCD137 可能是 HCC 发展的长期风险标志物。
