Proteoglycan-4 predicts good prognosis in patients with hepatocellular carcinoma receiving transcatheter arterial chemoembolization and inhibits cancer cell migration in vitro.
Proteoglycan-4 predicts good prognosis in patients with hepatocellular carcinoma receiving transcatheter arterial chemoembolization and inhibits cancer cell migration in vitro.
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DOI：
10.3389/fonc.2022.1023801
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发表时间：
2022
影响因子：
4.7
通讯作者：
Li, Hai Liang
中科院分区：
文献类型：
--
作者：
Guo, Yuan;Hu, Hong Tao;Xu, Shi Jun;Xia, Wei Li;Zhao, Yan;Zhao, Xiao Hui;Zhu, Wen Bo;Li, Fang Ting;Li, Hai Liang
关键词：
寻找影响肝动脉化疗栓塞（TACE）疗效的适应性反应分子，分析其与肝细胞癌（HCC）的临床相关性及预后价值，探讨其对细胞生物学行为的影响及其作用机制。肝癌组织基因测序用于鉴定差异表达的基因。采用酶联免疫吸附法检测117例接受TACE治疗的HCC患者血清中蛋白多糖4（PRG4）的表达。无血清培养基模拟TACE诱导的营养剥夺。构建PRG4稳定敲低的肝癌细胞（shPRG4），以验证PRG4对肝癌细胞体外生物学行为的影响及其机制。在TACE诱导的饥饿条件下，PRG4的表达显著升高。PRG4低表达与TACE治疗反应差、生存时间短和HCC迁移能力强相关。此外，体外实验表明PRG4的敲低通过增强上皮间质转化（EMT）促进HCC细胞迁移，而不影响增殖。当PRG4表达较低时，饥饿处理损害了HCC细胞的迁移能力，并降低了HCC细胞对表阿霉素的化疗敏感性。PRG4表达可预测HCC患者的生存率和TACE治疗反应。此外，PRG4的敲低增强了EMT，导致HCC细胞迁移。PRG4可作为接受TACE的HCC患者的生物标志物。
To search for adaptive response molecules that affect the efficacy of transcatheter arterial chemoembolization (TACE), analyze their clinical correlation with and prognostic value for hepatocellular carcinoma (HCC), and explore their impact on cell biological behavior and their mechanisms of action. HCC tissue gene sequencing was used to identify differentially expressed genes. The expression of proteoglycan 4 (PRG4) in the serum of 117 patients with HCC who received TACE was detected by enzyme-linked immunosorbent assay. Serum-free medium mimicked TACE-induced nutrient deprivation. Cells with stable knockdown of PRG4 (shPRG4) were constructed to verify the effect and mechanism of PRG4 on the biological behavior of HCC cells in vitro. The expression of PRG4 was significantly elevated under TACE-induced starvation conditions. Low PRG4 expression was associated with worse response to TACE treatment, shorter survival time, and stronger HCC migration ability. Furthermore, in vitro experiments showed that knockdown of PRG4 promoted HCC cell migration by enhancing epithelial–mesenchymal transition (EMT) while did not affect proliferation. When PRG4 expression was low, starvation treatment impaired the migratory ability of HCC cells and reduced the chemosensitivity of HCC cells to epirubicin. PRG4 expression predicts survival and TACE treatment response in patients with HCC. Furthermore, knockdown of PRG4 enhanced EMT, leading to HCC cell migration. PRG4 may serve as a biomarker for HCC patients receiving TACE.
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影响因子：
9
作者：
Dituri F;Scialpi R;Schmidt TA;Frusciante M;Mancarella S;Lupo LG;Villa E;Giannelli G
通讯作者：
Giannelli G
影响因子：
3.1
作者：
Kajihara, Jun;Tomimaru, Yoshito;Mori, Masaki
通讯作者：
Mori, Masaki
DOI：
10.1093/jnci/djx030
发表时间：
2017-09-01
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Jemal A;Ward EM;Johnson CJ;Cronin KA;Ma J;Ryerson B;Mariotto A;Lake AJ;Wilson R;Sherman RL;Anderson RN;Henley SJ;Kohler BA;Penberthy L;Feuer EJ;Weir HK
通讯作者：
Weir HK
肝细胞癌患者的治疗阶段迁移和治疗序列：缺点和机会。
影响因子：
3.6
作者：
Wehling C;Dill MT;Olkus A;Springfeld C;Chang DH;Naumann P;Longerich T;Kratochwil C;Mehrabi A;Merle U;Pfeiffenberger J;Rupp C;Weiss KH;Mieth M
通讯作者：
Mieth M
影响因子：
64.8
作者：
Kuma, A;Hatano, M;Mizushima, N
通讯作者：
Mizushima, N