Dysfunctional activation of neurotensin/IL-8 pathway in hepatocellular carcinoma is associated with increased inflammatory response in microenvironment, more epithelial mesenchymal transition in cancer and worse prognosis in patients.
Dysfunctional activation of neurotensin/IL-8 pathway in hepatocellular carcinoma is associated with increased inflammatory response in microenvironment, more epithelial mesenchymal transition in cancer and worse prognosis in patients.
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肝细胞癌中神经降压素/IL-8通路的功能失调性激活与微环境中炎症反应的增加、癌症中更多的上皮间质转化以及患者的预后较差相关
DOI：
10.1371/journal.pone.0056069
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hao X
中科院分区：
文献类型：
--
作者：
Yu J;Ren X;Chen Y;Liu P;Wei X;Li H;Ying G;Chen K;Winkler H;Hao X
Aim To investigate the role of neurotensin (NTS) in hepatocellular carcinoma (HCC) sub- grouping and the clinical and pathological significance of activation of NTS/IL-8 pathway in HCC. Methods The genome-wide gene expression profiling were conducted in 10 pairs of cancer tissues and corresponding normal adjacent tissues samples using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray to screen differentially expressing genes and enrich dysfunctional activated pathways among different HCC subgroups. The levels of NTS protein and multiple inflammation and epithelial mesenchymal transition (EMT) related proteins, including IL-8, VEGF, MMP9, CD68, E-Cadherin, β-Catenin and Vimentin were examined in 64 cases of paraffin-embedded HCC samples using immunohistochemistry (IHC) staining method. The clinical outcome and overall survival (OS) were compared. Results A subgroup of HCC characterized by up-regulated NTS expression was accompanied by up-regulated inflammatory responses and EMT. The direct interaction between NTS and IL-8 was identified by pathway enrichment analysis. Significantly increased IL-8 protein was confirmed in 90.91% of NTS+ HCC samples and significantly positively correlated to the levels of NTS protein in cancer tissues (P = 0.036), which implied activation of NTS/IL-8 pathway in HCC. The levels of VEGF and MMP9 correlated with co-expression of NTS and IL-8. Increased infiltration of CD68+ macrophages and more cancer cells displaying EMT features were found in NTS+IL-8+ samples. The co-expression of NTS and IL-8 in cancer significantly correlated with the clinical outcomes, as the mortality rate of NTS+IL-8+ HCC patients is 2.5-fold higher than the others after the surgery (P = 0.022). Accordingly, the OS of NTS+IL-8+ HCC patients significantly decreased who are under a higher hazard of death at an expected hazard ratio (HR) of 3.457. Conclusion Dysfunctional activation of the NTS/IL-8 pathway was detected in HCC which is associated with increased inflammatory response in microenvironment, enhanced EMT in cancer, and worse prognosis in HCC patients.
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影响因子：
8
作者：
Liao, Y-L;Sun, Y-M;Tsou, A-P
通讯作者：
Tsou, A-P
影响因子：
14.5
作者：
Andrisani OM;Studach L;Merle P
通讯作者：
Merle P
影响因子：
13.5
作者：
Ding, Wei;You, Hanning;Dang, Hien;LeBlanc, Francis;Galicia, Vivian;Lu, Shelly C.;Stiles, Bangyan;Rountree, C. Bart
通讯作者：
Rountree, C. Bart
影响因子：
5.8
作者：
Sivachenko, Andrey Y.;Yuryev, Anton
通讯作者：
Yuryev, Anton
影响因子：
3.7
作者：
Peng, Hsin-Hsin;Liang, Shile;Dong, Cheng
通讯作者：
Dong, Cheng