可溶性程序性细胞死亡-1预测核苷类似物治疗期间肝细胞癌的

StephenW

可溶性程序性细胞死亡-1预测核苷类似物治疗期间肝细胞癌的发展
Ritsuzo Kozuka 1 , Masaru Enomoto 2 , Minh Phuong Dong 1 , Hoang Hai 1 , Le Thi Thanh Thuy 1 , Naoshi Odagiri 1 , Kanako Yoshida 1 , Kohei Kotani 1 , Hiroyuki Motoyama 1 , Etsushi Kawamura 1 , Atsushi Hagihara 1 , Hideki Fujii 1 , Sawako Uchida-Kobayashi 1 , Akihiro Tamori 1 , Norifumi Kawada 1
隶属关系
隶属关系

    1
    大阪市立大学医学研究生院肝病学系，545-8585，大阪市阿倍野区旭町 1-4-3。
    2
    大阪市立大学医学研究生院肝病学系，545-8585，大阪市阿倍野区旭町 1-4-3。 [email protected]。

    PMID：34996935 DOI：10.1038/s41598-021-03706-w

抽象的

可溶性免疫检查点分子是新兴的免疫调节介质。然而，在慢性乙型肝炎病毒感染患者的核苷（酸）类似物（NA）治疗期间，可溶性免疫检查点蛋白是否影响肝细胞癌（HCC）的发展尚不清楚。这项研究包括 122 名接受 NA 治疗的 NA 初治患者。我们评估了临床因素（包括可溶性免疫检查点蛋白）与 NA 治疗期间 HCC 发展的关联。使用基于多路荧光珠的免疫测定法测量了 16 种可溶性免疫检查点蛋白的基线血清浓度。总共有 13 名患者在随访期间发展为 HCC（中位持续时间为 4.3 年）。在 16 种蛋白质中，可溶性 T 细胞共刺激物 (≥ 164.71 pg/mL; p = 0.014)、可溶性程序性细胞死亡 1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031)、可溶性 CD40 （≤ 493.68 pg/mL；p = 0.032）和可溶性疱疹病毒进入介质（≤ 2470.83 pg/mL；p = 0.038）与 HCC 发展显着相关（对数秩检验）。在多变量分析中，sPD-1 水平 ≤ 447.27 pg/mL（p = 0.014；风险比 [HR]，4.537）和甲胎蛋白水平 ≥ 6.4 ng/mL（p = 0.040；HR，5.524）独立且显着与 HCC 的发展有关。治疗前 sPD-1 是 NA 治疗期间 HCC 发展的新型预测生物标志物。

© 2022。作者。

StephenW

Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment
Ritsuzo Kozuka  1 , Masaru Enomoto  2 , Minh Phuong Dong  1 , Hoang Hai  1 , Le Thi Thanh Thuy  1 , Naoshi Odagiri  1 , Kanako Yoshida  1 , Kohei Kotani  1 , Hiroyuki Motoyama  1 , Etsushi Kawamura  1 , Atsushi Hagihara  1 , Hideki Fujii  1 , Sawako Uchida-Kobayashi  1 , Akihiro Tamori  1 , Norifumi Kawada  1
Affiliations
Affiliations

    1
    Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
    2
    Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan. [email protected].

    PMID: 34996935 DOI: 10.1038/s41598-021-03706-w

Abstract

Soluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. Pre-treatment sPD-1 is a novel predictive biomarker for HCC development during NA treatment.

© 2022. The Author(s).

StephenW

https://www.nature.com/articles/s41598-021-03706-w.pdf