Dual roles of WISP2 in the progression of hepatocellular carcinoma: implications of the fibroblast infiltration into the tumor microenvironment.
Dual roles of WISP2 in the progression of hepatocellular carcinoma: implications of the fibroblast infiltration into the tumor microenvironment.
复制标题
DOI：
10.18632/aging.203424
复制
发表时间：
2021-09-08
期刊：
影响因子：
--
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Jia Q;Zhang Y;Xu B;Liao X;Bu Y;Xu Z;Duan X;Zhang Q
肝细胞癌（HCC）患者预后不佳的原因是其转移和转移的频率高。识别有效的生物标志物是告知预后和提高生存率的关键策略。先前的研究报道了WISP2在癌变中的不一致作用，而WISP2在HCC进展中的作用也尚不清楚。在本研究中，我们通过多个在线数据集证实了WISP2在HCC组织中下调，并且WISP2是一种保护因子，特别是在没有酒精摄入的患者中。此外，我们在体外报道了HCC中WISP2的上调与恶性表型的抑制有关，但在体内未观察到这些改变。WISP2也与肿瘤纯度呈负相关，成纤维细胞浸润增加促进HCC组织的恶性进展。HCC中WISP2过表达后，成纤维细胞浸润能力增强与HMGB1上调有关。这些发现揭示了WISP2的抗癌作用，HMGB1是通过降低成纤维细胞浸润的肿瘤纯度来抑制WISP2效率的关键因素之一。
The dismal outcome of hepatocellular carcinoma (HCC) patients is attributable to high frequency of metastasis and. Identification of effective biomarkers is a key strategy to inform prognosis and improve survival. Previous studies reported inconsistent roles of WISP2 in carcinogenesis, while the role of WISP2 in HCC progression also remains unclear. In this study, we confirmed that WISP2 was downregulated in HCC tissues, and WISP2 was acting as a protective factor, especially in patients without alcohol intake using multiple online datasets. In addition, we reported that upregulation of WISP2 in HCC was related to inhibition of the malignant phenotype in vitro, but these alterations were not observed in vivo. WISP2 also negatively correlated with tumour purity, and increased infiltration of fibroblasts promoted malignant progression in HCC tissues. The enhanced infiltration ability of fibroblasts was related to upregulated HMGB1 after overexpression of WISP2 in HCC. The findings shed light on the anticancer role of WISP2, and HMGB1 is one of the key factors involved in the inhibition of the efficiency of WISP2 through reducing the tumour purity with fibroblast infiltration.