Hu Kuan, Wang Zhi-Ming, Li Juan-Ni, Zhang Sai, Xiao Zhong-Fu, Tao Yi-Ming
Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Transl Oncol. 2018 Apr;11(2):552-558. doi: 10.1016/j.tranon.2018.02.010. Epub 2018 Mar 8.
Spontaneous tumor hemorrhage (TH) is frequently observed in solid tumors including human hepatocellular carcinoma (HCC). TH implies fast-growing and worse tumor immunological microenvironment; however, the underlying mechanism remains largely unknown. CLEC1B is a signature gene highly associated with tumor progression. PD-L1 expression is a key biomarker predictive of immune checkpoint therapies, which showed astonishing effect on various types of tumor. We assume that, in HCC, TH may closely associate with the expression of these two molecules. In this study, 136 patients with HCC were enrolled. qRT-PCR showed that CLEC1B expression is significantly lower in HCC tumor tissue. Immunohistochemistry of HCC tissue microarrays demonstrated that PD-L1 and CLEC1B expressions were significantly correlated with TH and clinicopathological features indicating worse HCC progression. According to univariate/multivariate analysis, a combination of PD-L1 and CLEC1B expression was an independent prognostic factor indicating the poor outcome. The prognostic value of PD-L1 and CLEC1B was validated by Cox proportional-hazard analyses. Collectively, tumor with TH is closely associated with CLEC1B & PD-L1 expression, which may imply high response of PD-L1/PD-1 immune checkpoint therapies. CLEC1B may be a potential therapeutic target for PD-L1/PD-1 immunotherapy. PD-L1 and CLEC1B can be a valuable prognosis factor implying worse clinical outcomes.
自发性肿瘤出血（TH）在包括人类肝细胞癌（HCC）在内的实体瘤中经常可见。TH意味着肿瘤生长迅速且免疫微环境较差；然而，其潜在机制在很大程度上仍不清楚。CLEC1B是一个与肿瘤进展高度相关的标志性基因。程序性死亡受体配体1（PD-L1）表达是预测免疫检查点疗法的关键生物标志物，该疗法对各种类型的肿瘤都显示出惊人的效果。我们假设，在肝癌中，TH可能与这两种分子的表达密切相关。在本研究中，纳入了136例肝癌患者。定量逆转录聚合酶链反应（qRT-PCR）显示，CLEC1B在肝癌肿瘤组织中的表达显著降低。肝癌组织芯片的免疫组织化学结果表明，PD-L1和CLEC1B的表达与TH及提示肝癌进展更差的临床病理特征显著相关。根据单因素/多因素分析，PD-L1和CLEC1B表达的联合是提示预后不良的独立预后因素。PD-L1和CLEC1B的预后价值通过Cox比例风险分析得到验证。总体而言，伴有TH的肿瘤与CLEC1B和PD-L1表达密切相关，这可能意味着对PD-L1/程序性死亡受体1（PD-1）免疫检查点疗法有高反应性。CLEC1B可能是PD-L1/PD-1免疫治疗的潜在治疗靶点。PD-L1和CLEC1B可能是提示临床预后较差的有价值的预后因素。
