Data from immunohistochemical detection of CIC
Data from immunohistochemical detection of CIC-3 revealed that the immunostaining of CIC-3 can be present both in hepatocarcinoma and its matched normal controls though; CIC-3 was, on the whole, significantly elevated in hepatocarcinoma relative to its paired normal control. In consideration of the frequent possible false positive results from immunohistochemistry or in other words, the immunohistochemical data was subject to poor reproducibility on account of the compromised specificity and correctness of commercial primary antibodies, as previously and seriously revealed (Baker, 2015). To avoid these technical traps that were easy to fall into when performing immunohistochemistry, we were determined to pre-test the specificity of the primary antibody to CIC-3 from the outset of our immunohistochemistry experiment. The pre-evaluation verified the primary antibody to CIC-3 to be used can be adequately specific to do its job. Therefore, our immunohistochemical data was unlikely to be influenced by the potential compromised specificity of primary antibody we used. On the basis of understanding of CIC-3 expression in hepatocarcinoma, we then sought to analyze the clinicopathological significance of CIC-3 expression by means of Cross-Table analytical methods. It turned out to be that over-expressed CIC-3 only markedly correlated with tumor size and overall prognosis, while no significant correlation can be achieved with other clinicopathological variables including gender, age, clinical stage, T classification, lymph node metastasis, and differentiation degree. In light of no similar report has been available in hepatocarcinoma, it is thus improbable to make comparisons and bms my trials with similar peer studies undertaken in hepatocarcinoma. Despite this, in terms of prognosis, our observations were in line with two previous reports (Xu et al., 2015; Macpherson et al., 2014) reporting that CIC-3 was found to be significantly associated with poor prognosis. Our findings, therefore, confirm the prognostic value of CIC-3 in hepatocarcinoma.
What’s inconsistent with earlier investigations (Wang et al., 2017a, 2017b, Tamborini et al., 2016; Xu et al., 2015; Sontheimer, 2008) suggesting that CIC-3 could be related with metastasis, is in our own cases, we failed to observe CIC-3 expression correlated with lymph node metastasis in hepatocarcinoma. The possible explanations for the divergent results between ours and those previous studies could be explained: for one thing, our study was established on the basis of clinical tissues rather than in vitro hepatocellular cell lines, our study thus differs from those previous studies; secondly, the varying cut-off level for determining the high and low expression of CIC-3 when doing immunohistochemistry has been differently applied in ours and earlier studies by others could be another possible explanation. Although our study firstly described the predictive value of CIC-3 expression in tumor size and unfavorable overall survival in hepatocarcinoma, care also needs to be taken to interpret our data. First, future studies with larger sample size may be warranted; second, mechanistic insight should be got into on in vitro cell line level.
Conflict of interest
Introduction Ligand-gated chloride channels (LGCCs) play a physiologically important role as neurotransmitter receptors that commonly mediate inhibitory signals in the nervous systems of animals [1,2]. These chloride channels, including γ-aminobutyric acid (GABA)-gated chloride channels (GABACls), glycine-gated chloride channels (GlyCls), and glutamate-gated chloride channels (GluCls), belong to the Cys-loop family of ion channels, the members of which are comprised of five homologous subunits . Each subunit has an extracellular domain, which contains agonist-binding loops, and four transmembrane regions (TMs), the second of which lines the channel pore. While human LGCCs are important targets for drugs , invertebrate LGCCs serve as targets for pest control agents .