Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma.
Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma.
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B7-H4的上调促进肝内胆管癌的肿瘤进展
DOI：
10.1038/s41419-017-0015-6
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发表时间：
2017-12-13
影响因子：
9
通讯作者：
Shi GM
中科院分区：
文献类型：
--
作者：
Xie N;Cai JB;Zhang L;Zhang PF;Shen YH;Yang X;Lu JC;Gao DM;Kang Q;Liu LX;Zhang C;Huang XY;Zou H;Zhang XY;Song ZJ;Sun HX;Fu BM;Ke AW;Shi GM
最近的研究表明，B7-H4在多种肿瘤细胞中高表达，作为T细胞的负调节因子，进而促进肿瘤进展。然而，其在肝内胆管癌（ICC）中的表达和作用仍不清楚。本研究在mRNA和蛋白水平上测定了ICC和瘤周组织中B7-H4的表达，并在修饰B7-H4表达后研究了其在ICC细胞中的生物活性。然后，探讨了ICC细胞中B7-H4表达诱导肿瘤进展的相关机制。最后进一步分析ICC患者中B7-H4表达的临床意义。结果显示，B7-H4在ICC中的mRNA和蛋白表达水平均远高于瘤周组织。 ICC细胞中高水平的B7-H4通过激活ERK1/2信号诱导上皮间质转化并促进肿瘤细胞的侵袭和转移。 B7-H4 表达升高与 Bax 下调、Bcl-2 表达上调和 caspase-3 激活相关。临床上，肿瘤样本中B7-H4的高表达与恶性表型显着相关，如淋巴结转移、肿瘤分期高、分化差等。 B7-H4 高表达的 ICC 患者总生存期 (OS) 和无病生存期较短。此外，B7-H4 表达是预测 ICC 患者术后 OS 和肿瘤复发的独立预后因素。总之，B7-H4 的高表达促进 ICC 肿瘤进展，可能成为 ICC 患者的新治疗靶点。
Recent reports show that B7-H4 is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and then promotes tumor progression. However, its expression and role in intrahepatic cholangiocarcinoma (ICC) remain unclear. In present study, B7-H4 expression in ICC and peritumoral tissues was determined at the level of mRNA and protein, and its bioactivity in ICC cells was studied after modification of B7-H4 expression. Then, the mechanism related to tumor progression induced by B7-H4 expression in ICC cells was explored. Finally, clinical significance of B7-H4 expression in ICC patients was further analyzed. The results showed that B7-H4 expression in ICC was much higher than that in peritumoral tissues at the level of both mRNA and protein. The high level of B7-H4 in ICC cells induced epithelial-to-mesenchymal transitions and promoted invasion and metastasis of tumor cells through activation of ERK1/2 signaling. The elevated B7-H4 expression was associated with the downregulated Bax, upregulated Bcl-2 expression, and activation of caspase-3. Clinically, high B7-H4 expression in tumor samples was significantly related to malignant phenotype, such as lymph node metastasis, high tumor stage, and poor differentiation. ICC patients with high expression of B7-H4 had shorter overall survival (OS) and disease-free survival. Moreover, the B7-H4 expression was an independent prognostic factor for predicting OS and tumor recurrence of ICC patients after operation. In conclusion, high expression of B7-H4 promotes tumor progression of ICC and may be a novel therapeutic target for ICC patients.
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影响因子：
9.7
作者：
Song, Hyunkeun;Park, Gabin;Hur, Dae Young
通讯作者：
Hur, Dae Young
影响因子：
--
作者：
Chong DQ;Zhu AX
通讯作者：
Zhu AX
B7-H4(B7x)介导的胶质瘤起始细胞和巨噬细胞之间通过IL6/JAK/STAT3途径的串扰导致胶质瘤患者预后不良
DOI：
10.1158/1078-0432.ccr-15-0858
发表时间：
2016-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Yao Y;Ye H;Qi Z;Mo L;Yue Q;Baral A;Hoon DSB;Vera JC;Heiss JD;Chen CC;Zhang J;Jin K;Wang Y;Zang X;Mao Y;Zhou L
通讯作者：
Zhou L
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
B-晶状体蛋白与 14-3-3 复合物诱导肝细胞癌上皮间质转化和索拉非尼耐药
影响因子：
13.5
作者：
Huang, Xiao-Yong;Ke, Ai-Wu;Zhou, Jian
通讯作者：
Zhou, Jian