Evaluation of the prognostic significances of γ-secretase genes in pancreatic cancer

Oncol Lett. 2019 May;17(5):4614-4620. doi: 10.3892/ol.2019.10113. Epub 2019 Mar 5.


With the growing requirement for novel prognostic biomarkers for pancreatic cancer, many studies have focused on clinical and/or genomic variables. Although many studies have been performed, carbohydrate antigen 19-9 is the only biomarker in clinical use. Therefore, the present study examined whether γ-secretase genes, including presenilin (PSEN), nicastrin (NCSTN), presenilin enhancer protein 2 (PSENEN), and anterior pharynx-defective 1 (APH1-), could serve as prognostic factors for pancreatic cancer. The cohorts selected included >100 pancreatic cancer patients. Patient data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GSE21501). The prognostic roles of the γ-secretase genes were analyzed by several survival analysis methods. Among the γ-secretase genes, the prognosis tended to be worse in the 2 cohorts with increasing expression of PSEN1, APH1A, and PSENEN, while the remaining genes were the opposite in the 2 cohorts. Notably, although the patient characteristics were quite different, APH1A was statistically significantly associated with prognosis in the 2 cohorts. The hazard ratio of APH1A for overall survival was 1.598 (TCGA) and 2.724 (GSE21501). These results contribute to the study of γ-secretase in pancreatic cancer. We believe that γ-secretase, particularly APH1A, will be a new prognostic biomarker for pancreatic cancer.

Keywords: Gene Expression Omnibus; Notch signaling; The Cancer Genome Atlas; pancreatic cancer; prognosis; γ-secretase.