High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer.

Abstract

Pancreatic cancer is associated with an exceedingly poor prognosis, warranting the development of novel therapeutic strategies and discovery of prognostic predictors. Given that chemoresistance-related molecules are reportedly associated with the poor prognosis of pancreatic cancer, the present study aimed to identify molecules that could be efficacious therapeutic targets for pancreatic cancer. First, 10 patient-derived xenografts (PDXs) were established from patients with pancreatic cancer. Subsequently, after treating tumor tissue generated from the PDXs with standard drugs, next-generation sequencing (NGS) was performed using these tissues. The results of NGS analysis and immunohistochemical analysis on 80 pancreatic cancer tissues revealed that human epididymis protein 4 (HE4) expression in the anticancer drug-treated PDX group was higher than that in the untreated PDXs. In addition, chemoresistance ability was observed in tumor cell lines overexpressing HE4. Furthermore, Kaplan-Meier analysis of tumor tissues from 80 patients with pancreatic cancer was performed and it was found that patients with a high HE4 expression level had a poor survival rate compared with those who had a low HE4 expression level. Multivariate analysis also indicated the high expression level of HE4 was an independent poor prognostic biomarker. Thus, it was concluded that high gene and protein expression levels of HE4 mediate chemoresistance and are independent prognostic factors for pancreatic cancer.