Article Text
Abstract
Introduction/Background*In our previous microarray study we identified a set of genes (multigene signature) related with different survival of patients with high-grade serous ovarian cancer (HG-SOC) [1]. One of the genes from this signature was LOX, encoding for lysyl oxidase. LOX is engaged in the cross-linking of the extracellular matrix proteins. Various studies have indicated that LOX may act as either an oncogene or a tumor suppressor, depending on the type of tissue/tumor. As our previous study indicated that higher LOX mRNA level was negatively correlated with survival of ovarian cancer patients, we aimed to check whether LOX level determined by immunohistochemistry shows the same dependency and could be useful for clinical practice.
Methodology Two commercially available anti-LOX antibodies (ab174316-Abcam, NB-2530-Novus Biologicals) were validated by western blotting, using protein extracts from six ovarian cancer cell lines and recombinant LOX protein as a control (NBP-59887-Novus Biologicals). Then, immunohistochemical analysis was performed (tissue samples of HG-SOC) and on tissue arrays containing spectrum of different histological type, FIGO stages, etc. (US Biomax). The results were analyzed using Statistica (version-13.1, StatSoft Poland).
Result(s)*Only one antibody (ab174316-Abcam) was positively validated as specific toward LOX and it was used for further analysis. Unfortunately, Kaplan-Meier analysis showed no correlation between LOX protein level and the patients‘ survival time. Further analysis revealed that LOX level was correlated with primary/metastatic tumor difference: higher stromal LOX expression occurred eight times more often in metastatic than in primary tumors. However, there was no such correlation when LOX expression was assessed in cancer cells.
Conclusion*Although our previous observations indicated that higher LOX mRNA level was correlated with shorter survival of ovarian cancer patients, protein level of LOX does not demonstrate prognostic value in the analyzed group of patients with HG-SOC. However, we observed significantly higher LOX expression in the stroma of metastases compared to that of primary tumors. This observation is consistent with the assumption that LOX is associated with a more aggressive tumor phenotype.
[1] Katarzyna Lisowska et al. doi: 10.1007/s00432-016-2147-y
Acknowledgments This study was supported from grant Miniatura 3 (2019/03 /X/NZ5/00564) from National Science Center. A.J.C. was co-financed by the European Union through the European Social Fund (grant no. POWR.03.02.00–00–I029)