Doublecortin and CaM kinase-like-1 as an independent prognostic factor in patients with resected pancreatic carcinoma

AIM To elucidate the effect of expression of doublecortin and Ca M kinase-like-1(DCLK1) in patients with pancreatic ductal adenocarcinoma(PDAC). METHODS Tumor specimens were obtained from 136 patients with pancreatic cancer who had undergone resection without preoperative therapy between January 2000 and December 2013 at the Department of Surgical Oncology, Osaka City University. The resected specimens were analyzed for associations with clinicopathological data, including DCLK1 expression, epithelial mesenchymal transition(EMT) marker expression, and cancer stem cell(CSC) marker expression. Univariate and multivariate survival analyses were performed and we assessed the association between DCLK1 expression and clinicopathological factors, including the EMT marker and CSC marker.RESULTS In total, 48.5%(66/136) of the pancreatic cancer samples were positive for DCLK1. Patients with DCLK1-positive tumors had significantly shorter survival times than those with DCLK1-negative tumors(median, 18.7 mo vs 49.5 mo, respectively; P < 0.0001). Positive DCLK1 expression correlated with histological grade(P = 0.0290), preoperative CA19-9 level(P = 0.0060), epithelial cell adhesion molecule(Ep CAM) expression(P = 0.0235), and the triple-positive expression of CD44/CD24/Ep CAM(P = 0.0139). On univariate survival analysis, five factors were significantly associated with worse overall survival: histological grade of G2 to G4(P = 0.0091), high preoperative serum SPan-1 level(P = 0.0034), R1/2(P < 0.0001), positive expression of DCLK1(P < 0.0001) or CD44(P = 0.0245). On multivariate survival analysis, R1/2 [odds ratio(OR) = 2.019, 95% confidence interval(CI): 1.380-2.933; P = 0.0004] and positive DCLK1 expression(OR = 1.848, 95%CI: 1.2854-2.661; P = 0.0009) were independent prognostic factors. CONCLUSION DCLK1 expression was found to be an independent prognostic factor and it may play a crucial prognostic role by promoting acquisition of stemness.

Integrated genome-wide differentiation and association analyses identify causal genes underlying breeding-selected grain quality traits in japonica rice

Improving grain quality is a primary objective in contemporary rice breeding.Japanese modern rice breeding has developed two different types of rice,eating and sake-brewing rice,with different grain characteristics,indicating the selection of variant gene alleles during the breeding process.Given the critical importance of promptly and efficiently identifying genes selected in past breeding for future molecular breeding,we conducted genome scans for divergence,genome-wide association studies,and map-based cloning.Consequently,we successfully identified two genes,OsMnS and OsWOX9D,both contributing to rice grain traits.OsMnS encodes a mannan synthase that increases the white core frequency in the endosperm,a desirable trait for sake brewing but decreases the grain appearance quality.OsWOX9D encodes a grass-specific homeobox-containing transcription factor,which enhances grain width for better sake brewing.Furthermore,haplotype analysis revealed that their defective alleles were selected in East Asia,but not Europe,during modern improvement.In addition,our analyses indicate that a reduction in grain mannan content during African rice domestication may also be caused a defective OsMnS allele due to breeding selection.This study not only reveals the delicate balance between grain appearance quality and nutrition in rice but also provides a new strategy for isolating causal genes underlying complex traits,based on the concept of“breeding-assisted genomics”in plants.