Human complement factor H is a novel diagnostic marker for lung adenocarcinoma

Abstract

Abstract.Human complement factor H (cfH), a central complement control protein, is a member of the regulators of complement activation family. recent studies suggested that cfH may play a key role in the resistance of complementmediated lysis in various cancer cells. in this study, we investigated the role of cfH in human lung cancer. expression of cfH was analyzed in lung cancer cell lines by rt-Pcr, Western blotting and immunofluorescence. In primary lung tumors, the protein expression of cfH was evaluated by immunohistochemistry (iHc) on tissue microarray (tMa). Binding of cfH to lung cancer cells was detected by flow cytometry. mrna expression of cfH was detected in 6 out of 10 non-small cell lung cancer (nSclc) cell lines, but in none of the small cell lung cancer (Sclc) cell lines. in line with Western blotting, immunofluorescence analysis demonstrated cfH protein expression in 3 nSclc cell lines, and the immunoreaction was mainly associated with cell cytoplasm and membrane. in primary lung tumors, 54 out of 101 samples exhibited high expression of cfH and high expression was significantly correlated with lung adenocarcinoma (p=0.009). also, in adenocarcinoma of the lung, Kaplan-Meier survival analysis showed a tendency that cfH-positive tumors had worse prognosis in comparison to cfH-negative tumors (p=0.082). Additionally, shorter survival time of patients with adenocarcinoma (<20 months) was associated with higher staining of CFH (p=0.033). Our data showed that non-small cell lung cancer cells expressed and secreted cfH. cfH might be a novel diagnostic marker for human lung adenocarcinoma.

Local expression of complement factor I in breast cancer cells correlates with poor survival and recurrence

“…Kaplan-Meier analyses of cancerspecific survival (CSS) and recurrence-free survival (RFS) revealed statistically significant differences between patients bearing tumors with weak and strong expression of FI (p values 0.004 and < 0.001, respectively) (Fig.4). Also, FI expression in stroma associated with RFS, but experiments [5] and suggested by immunohistochemical staining of tumor tissue obtained from patients [30]. Interestingly for our study, FH is one of the main cofactors required for the activity of FI.…”

Integrated Pathway Clusters with Coherent Biological Themes for Target Prioritisation

“…The above association would not have been identified by the standard pathway analysis, because Cfh was mapped to three Reactome pathways REACT_86987 “Innate Immune System”, REACT_144679 “Regulation of Complement cascade” and REACT_103920 “Complement cascade”, which were components of no005 but individually, none of the three pathways showed significant association with the original gene set ( p  = 0.3206, p  = 0.3430 and p  = 0.6079, respectively) (Table S4B). Our observations appear to be consistent with previous studies, which have shown that the human orthologue of mouse Cfh is associated with the early stages of lung tumourigenesis [21], [22]. These results demonstrate the relative ease of identifying enriched biological processes previously shown to play critical roles in Stat3-dependent carcinogen-induced lung tumourigenesis [18] and the ability of our approach to identify a novel biological theme not identifiable by previous methods.…”

The Role of Complement in Tumor Growth

“…This resistance may be mediated by the expression and secretion of factor H and FHL-1 to the extracellular milieu (Ajona et al 2004). Downregulation of factor H reduces the growth of lung cancer cells in vivo (Ajona et al 2007), and its expression in lung adenocarcinomas may be associated with worse prognosis (Cui et al 2011). …”