TITLE

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

AUTHOR(S)
Yu, Jinpu; Ren, Xiubao; Chen, Yongzi; Liu, Pengpeng; Wei, Xiyin; Li, Hui; Ying, Guoguang; Chen, Kexin; Winkler, Hans; Hao, Xishan
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
87624258

 

Related Articles

  • A Method to Correlate mRNA Expression Datasets Obtained from Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Tissue Samples: A Matter of Thresholds. Mustafa, Dana A. M.; Sieuwerts, Anieta M.; Smid, Marcel; de Weerd, Vania; van der Weiden, Marcel; Meijer - van Gelder, Marion E.; Martens, John W. M.; Foekens, John A.; Kros, Johan M. // PLoS ONE;12/30/2015, Vol. 10 Issue 12, p1 

    Background: Gene expression profiling of tumors is a successful tool for the discovery of new cancer biomarkers and potential targets for the development of new therapeutic strategies. Reliable profiling is preferably performed on fresh frozen (FF) tissues in which the quality of nucleic acids...

  • Histological Assessment of PAXgene Tissue Fixation and Stabilization Reagents. Kap, Marcel; Smedts, Frank; Oosterhuis, Wolter; Winther, Rosa; Christensen, Nanna; Reischauer, Bilge; Viertler, Christian; Groelz, Daniel; Becker, Karl-Friedrich; Zatloukal, Kurt; Langer, Rupert; Slotta-Huspenina, Julia; Bodo, Koppany; Jong, Bas de; Oelmuller, Uwe; Riegman, Peter // PLoS ONE;2011, Vol. 6 Issue 11, p1 

    Within SPIDIA, an EC FP7 project aimed to improve pre analytic procedures, the PAXgene Tissue System (PAXgene), was designed to improve tissue quality for parallel molecular and morphological analysis. Within the SPIDIA project promising results were found in both genomic and proteomic...

  • High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection. von Felden, Johann; Heim, Denise; Schulze, Kornelius; Krech, Till; Ewald, Florian; Nashan, Björn; Lohse, Ansgar W.; Wege, Henning // BMC Cancer;1/18/2017, Vol. 17, p1 

    Background: Hepatocellular carcinoma has a dismal prognosis due to recurrence rates of up to 70% after curative resection. Early recurrence is driven by synchronous microscopic intrahepatic metastases. The predictive value of histological parameters is discussed controversially and...

  • Gene expression profiling reveals GC and CEACAM1 as new tools in the diagnosis of lung carcinoids. Toffalorio, F; Belloni, E; Barberis, M; Bucci, G; Tizzoni, L; Pruneri, G; Fumagalli, C; Spitaleri, G; Catania, C; Melotti, F; Pelicci, P G; Spaggiari, L; De Pas, T // British Journal of Cancer;3/4/2014, Vol. 110 Issue 5, p1244 

    Background:Classification of lung carcinoids into typical and atypical is a diagnostic challenge since no immunohistochemical tools are available to support pathologists in distinguishing between the two subtypes. A differential diagnosis is essential for clinicians to correctly discuss therapy,...

  • Comparison of histopathology to gene expression profiling for the diagnosis of metastatic cancer. Kulkarni, Anand; Pillai, Raji; Ezekiel, Ashley M.; Henner, W. David; Handorf, Charles R. // Diagnostic Pathology;2012, Vol. 7 Issue 1, p110 

    Background: Determining the primary site of metastatic cancer with confidence can be challenging. Pathologists commonly use a battery of immunohistochemical (IHC) stains to determine the primary site. Gene expression profiling (GEP) has found increasing use, particularly in the most difficult...

  • Effects of pinacidil on changes to the microenvironment around the incision site, of a skin/muscle incision and retraction, in a rat model of postoperative pain. SU CAO; YINBIN QIN; JUNJIE CHEN; SHIREN SHEN // Molecular Medicine Reports;2015, Vol. 12 Issue 1, p829 

    The aim of the present study was to evaluate the influence of the microenvironment around an incision site, on peripheral and central sensitization. The effects of pinacidil activation of ATP-sensitive potassium (KATP) channels prior to skin/muscle incision and retraction (SMIR) surgery were...

  • Isolation and Characterization of a Metastatic Hybrid Cell Line Generated by ER Negative and ER Positive Breast Cancer Cells in Mouse Bone Marrow. De Mukhopadhyay, Keya; Bandyopadhyay, Abhik; Chang, Ting-Tung A.; Elkahloun, Abdel G.; Cornell, John E.; Junhua Yang; Goins, Beth A.; Yeh, I-Tien; Lu-Zhe Sun // PLoS ONE;2011, Vol. 6 Issue 6, p1 

    Background: The origin and the contribution of breast tumor heterogeneity to its progression are not clear. We investigated the effect of a growing orthotopic tumor formed by an aggressive estrogen receptor (ER)-negative breast cancer cell line on the metastatic potential of a less aggressive...

  • Immunohistochemical diagnosis of Fabry nephropathy and localisation of globotriaosylceramide deposits in paraffin-embedded kidney tissue sections. Valbuena, Carmen; Leitão, Dina; Carneiro, Fátima; Oliveira, João // Virchows Archiv;Feb2012, Vol. 460 Issue 2, p211 

    Fabry disease (FD) is a rare X-linked lysosomal storage disorder of glycosphingolipids, mostly globotriaosylceramide (Gb3). Proteinuric chronic kidney disease develops frequently, and recognition of Fabry nephropathy on a kidney biopsy may be the first clue to the underlying diagnosis. Since the...

  • Immunohistochemical detection of Hsp90 and Ki-67 in pterygium. Sebastiá, Roberto; Ventura, Marcelo Palis; Solari, Helena Parente; Antecka, Emilia; Orellana, Maria Eugenia; Burnier Jr., Miguel N. // Diagnostic Pathology;2013, Vol. 8 Issue 1, p1 

    Background: To examine the immunohistochemical expression of heat shock protein 90 (Hsp90) and Ki-67 protein in human pterygium. Materials and methods: Tissues obtained during pterygium surgery of 15 patients who underwent the bare-sclera procedure and 10 normal conjunctivae were studied. All of...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics