DEK protein overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma

Abstract

DEK, a transcription factor, is involved in mRNA splicing, transcriptional control, cell division and differentiation. Recent studies suggest that DEK overexpression can promote tumorigenesis in a wide range of cancer cell types. However, little is known concerning the status of DEK in pancreatic ductal adenocarcinoma (PDAC). Based on the microarray data from Gene Expression Omnibus (GEO), the expression levels of DEK mRNA in PDAC tissues were significantly higher than levels in the adjacent non-tumor tissues. To explore the clinical features of DEK overexpression in PDAC, 87 PDAC and 52 normal pancreas tissues were selected for immunoenzyme staining of the DEK protein. Localization of the DEK protein was detected in PANC-1 pancreatic cancer cells using immunofluorescence (IF) staining. The correlations between DEK overexpression and the clinical features of PDAC were evaluated using the Chi-squared (χ2) and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. The expression levels of DEK mRNA in PDAC tissues were significantly higher than that in the adjacent non‑tumor tissues. The DEK protein showed a primarily nuclear staining pattern in PDAC. The positive rate of the DEK protein was 52.9% (46/87) in PDAC, which was significantly higher than that in the adjacent normal pancreatic tissues (7.7%, 4/52). DEK overexpression in PDAC was correlated with tumor size, histological grade, tumor‑node‑metastasis (TNM) stage and overall survival (OS) rates. In addition, multivariate analysis demonstrated that DEK overexpression was an independent prognostic factor along with histological grade and TNM stage in patients with PDAC. In conclusion, DEK overexpression is associated with PDAC progression and may be a potential biomarker for poor prognostic evaluation in PDAC.

DEK overexpression is predictive of poor prognosis in esophageal squamous cell carcinoma

“…Multivariate survival analysis confirmed DEK overexpression as an independent predictive factor of poor survival in ESCC, alongside TNM stage and lymph node metastasis (Table III). The association of DEK overexpression with disease-free survival or survival rates was consistent with other studies which reported that increased DEK expression was clearly correlated with poor prognosis in other solid tumors [7,31,32]. Sun et al demonstrated that patients with high DEK expression had a lower overall survival rate than those with low DEK expression [31].…”

“…Similarly, the rate of DEK overexpression was considerably increased in poorly differentiated esophageal cancer (85.1%) compared with moderately and well-differentiated cancers (39.7%, p < 0.001). Several studies have also reported that DEK overexpression was significantly related to clinical prognostic parameters [23,[31][32][33]. Liu et al reported that DEK expression level is considerably higher in invasive ductal breast cancer compared with normal breast tissue and associated with proliferation (Ki-67 levels) and histological grade, indicating that DEK might potentially be an indicator for early detection and prognosis [32].…”

“…Liu et al reported that DEK expression level is considerably higher in invasive ductal breast cancer compared with normal breast tissue and associated with proliferation (Ki-67 levels) and histological grade, indicating that DEK might potentially be an indicator for early detection and prognosis [32]. Sun et al reported that DEK overexpression was strongly related to histological grade and TNM stage which indicated poor prognosis and recurrence in patients with pancreatic ductal adenocarcinoma (PDAC) [31]. Riveiro-Falkenbach et al demonstrated that DEK expression was significantly positive in malignant lesions of melanoma, especially in metastatic cases, and correlated with histological features of aggressiveness [23].…”

“…DEK overexpression was reflected by '++' or '+++' score. In survival analyses, DEK expression was classified as low expression ('-' and '+') and high expression ('++' and '+++') [11,26,31].…”

A role for intracellular and extracellular DEK in regulating hematopoiesis

“…DEK was originally discovered as part of the fusion protein DEK-NUP214 (i.e. DEK-CAN), a result of a t(6;9) chromosome translocation in a subset of patients with acute myelogenous leukemia [1–4*], and as an oncoprotein in various neoplasms including melanoma [5–7*], breast cancer [8], glioblastoma [9], hepatocellular carcinoma [10, 11*], retinoblastoma [12, 13], gastric adenocarcinoma [14*], non-small cell lung cancer [15*], pancreatic ductal adenocarcinoma [16*], and bladder cancer [17]. DEK was found to be a regulator of hematopoiesis controlling HSC and HPC numbers/fate decision [18, 19].…”