为肝细胞癌武装 GPC3 CAR-T 细胞：多少才足够，下一步是什么？
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
聚（ADP-核糖）聚合酶 1 结合蛋白表达与 CD8⁺ TIL（肿瘤浸润淋巴细胞）在肝细胞癌中的预后意义
英文原题：Prognostic Significance of Poly (ADP-Ribose) Polymerase 1 Binding Protein Expression and CD8(+) Tumor-Infiltrating Lymphocytes in Hepatocellular Carcinoma.
查看英文原题
Prognostic Significance of Poly (ADP-Ribose) Polymerase 1 Binding Protein Expression and CD8(+) Tumor-Infiltrating Lymphocytes in Hepatocellular Carcinoma.
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中文摘要
聚（腺苷二磷酸［ADP］核糖）聚合酶 1 结合蛋白（PARPBP）在肝细胞癌（HCC）预后中的作用尚不明确。本研究检测 HCC 临床样本中的 PARPBP 表达，并评估其与 CD8⁺ TIL（肿瘤浸润淋巴细胞）相关的临床病理学意义。研究评估了 96 例 HCC 患者手术标本中的 PARPBP 表达及 CD8⁺ TIL 密度；采用免疫组织化学测定 PARPBP 蛋白水平，并分析其与临床病理特征和患者结局的关系；另在 Huh7 细胞中使用多西环素诱导的靶向 PARPBP 短发夹 RNA 系统进行实验。
结果显示，中分化和低分化 HCC 的 PARPBP 表达显著高于高分化肿瘤。PARPBP 高表达患者的无复发生存期和总生存期均短于低表达患者（两者均 P < .001）。多变量分析显示，PARPBP 高表达（风险比［HR］2.806，P = .002）、CD8⁺ TIL 密度高（HR 0.148，P < .001）以及甲胎蛋白 10 ng/mL（HR 1.904，P = .047）是独立预后因素。联合分析发现，PARPBP 高表达且 CD8⁺ TIL 密度低的患者无复发生存和总生存期结局最差（两者均 P < .001）。体外实验显示，PARPBP mRNA 在肝癌细胞系中的表达高于正常肝细胞，敲低 PARPBP 可抑制 Huh7 细胞增殖。
总之，PARPBP 表达升高与 HCC 分化较差及生存不良相关；同时考量 PARPBP 高表达和 CD8⁺ TIL 密度低可提高预后判断准确性。
展开英文摘要原文
The role of poly (adenosine diphosphate [ADP]-ribose) polymerase 1 binding protein (PARPBP) in hepatocellular carcinoma (HCC) prognosis remains unclear.
This study investigated PARPBP expression in HCC clinical samples and evaluated its clinicopathological significance in relation to CD8-positive tumor-infiltrating lymphocytes (CD8 + TILs). PARPBP expression and CD8 + TIL density were assessed in surgical specimens from 96 patients with HCC.
We performed immunohistochemical analysis to determine PARPBP protein levels, which were correlated with clinicopathological features and patient outcomes.
Additionally, we performed experiments using a doxycycline-inducible short hairpin RNA system targeting PARPBP in Huh7 cells. Results indicated that moderately and poorly differentiated HCC had significantly higher PARPBP expression than well-differentiated tumors. Patients with high PARPBP expression exhibited shorter recurrence-free survival and overall survival than those with low expression (both P < . 001). Multivariate analysis showed that high PARPBP expression (hazard ratio [HR], 2. 806; P = .
002), high CD8 + TIL density (HR, 0. 148; P < . 001), and -fetoprotein 10 ng/mL (HR, 1. 904; P = . 047) were independent predictors of prognosis. Combined analysis revealed that patients with high PARPBP expression and low CD8 + TIL density had the worst recurrence-free survival and overall survival outcomes (both P < . 001). In vitro experiments showed that the mRNA expression of PARPBP was higher in liver cancer cell lines than in normal liver cells and that PARPBP knockdown suppressed huh7 cell proliferation.
In conclusion, elevated PARPBP expression was associated with poor differentiation and survival in patients with HCC.
Furthermore, the combination of high PARPBP expression and low CD8 + TIL density improved prognostic accuracy.
论文信息
- 作者
- Okada M、Sato-Matsubara M、Enomoto M、Hoang TH、Uchida-Kobayashi S、Tamori A、Matsubara T、Kohashi K
- 第一作者单位
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.Japan
- 通讯作者单位
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan; Endowed Department of Homeostatic Regulation, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan; Endowed Department of Liver Cancer Treatment, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan. Electronic address: kawadanori@omu.ac.jp.Japan
- 期刊
- Laboratory investigation; a journal of technical methods and pathology2025 Nov
- 原文标识
- PubMed 40780543 · DOI 10.1016/j.labinv.2025.104226