Abstract
Background
Ovarian cancer has a high mortality rate due to difficulties in early detection and chemotherapy resistance. Human epididymal protein 4 (HE4) has been adopted as a novel serum biomarker for early ovarian cancer diagnosis, we have previously detected the presence of Lewis y antigen modifications on HE4 in ovarian cancer cell lines. In this study, we aimed to analyze the expression of HE4 and Lewis y antigen in human ovarian cancer in order to analyze their correlation with each other, as well as with the clinical pathological parameters of ovarian cancer patients.
Methods
We first used immunohistochemistry to detect the respective expressions of these compounds in two patient groups (chemotherapy-resistant and -sensitive) containing a total of 95 patients. Then, we adopted a bioinformatic approach and used online large-sample databases (TCGA, CCLE and GTEx; Metascape, Cytoscape) to explore the potential mechanisms of action of these compounds.
Results
Our results demonstrate that high HE4 and Lewis y expressions could be used as markers for chemotherapy-resistance and poor prognosis in ovarian cancer patients. These two expressions were widely correlated in various cancer tissues and are thought to act by activating the p38 MAPK pathway and inducing VEGFA, PTGS2,EGR1,andHIFI1A, thereby promoting malignant biological behavior and resistance in ovarian cancer.
Conclusions
This finding not only reveals the possible mechanism by which HE4 and Lewis y antigen affect ovarian cancer, but also identifies a four-gene signature that could be very useful in ovarian cancer detection and/or the development of new targeted therapies.
Expression of Lewis y antigen and integrin αv, β3 in ovarian cancer and their relationship with chemotherapeutic drug resistance
