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.

双皮质核素钙调素依赖性激酶-1和Ki-67在胰大部切除术后的表达及分布

目的：观察大鼠胰大部分切除术后双皮质核素钙调素依赖性激酶-1 （DCAMKL-1）和Ki-67在胰组织中的表达及分布,探讨胰岛再生的调控机制.方法：成年SD大鼠随机分为正常对照组、模型组,手术切除胰60％～70％后1、2、3、4、5、6d分别取残存胰,免疫组织化学PV-9001显色观察DCAMKL-1和Ki-67在胰组织内的表达及分布.结果：DCAMKL-1和Ki-67在正常胰组织有少量表达,表达主要分布在导管、胰岛和腺泡之间的间质.模型组术后1d,主胰管周围可见大量细胞呈蜂窝状样排列,DCAMKL-1和Ki-67表达显著增高,3d时细胞明显增多并在主导管周围出现导管样结构,DCAMKL-1和Ki-67表达达到顶峰,4d后开始下降,但至6d时仍高于正常.与正常对照组相比,DCAMKL-1在腺泡及胰岛内表达变化不明显,而Ki-67术后5d时达到高峰,6d下降.结论：胰大部切除后,胰主导管及周围大量DCAMKL-1阳性细胞增殖,DCAMKL-1阳性细胞可能为胰干细胞.

双肾上腺皮质激素样激酶-1与细胞周期蛋白D1在结直肠癌组织中的表达及临床意义

目的：探讨双肾上腺皮质激素样激酶-1（EgJLKl）与细胞周期蛋白D1（cyclin D1）在结直肠癌组织中的表达及其临床意义。方法：采用免疫组织化学S-ABC法检测59例结直肠癌组织和28例结直肠良性病变组织中DCI。K1及cyclinD1的表达及分布。结果：DCLK1及cyclin D1在结直肠癌组织中的表达明显高于结直肠良性病变组织，平均光密度值（AOD）为0．423±0．021及0．386±0．042；而在结直肠良性病变组织中其阳性反应的平均光密度值为0．267±0．053及0．21l±0．026，差异具有统计学意义。DCLK1及cyclinD1的阳性表达与患者的年龄、性别、肿瘤分化程度和DUCKs分期无关，而与组织良性或恶性、肿瘤的大小及淋巴结转移相关。结论：结直肠癌组织中DCLKl及cyclinD1的高表达可能与结直肠癌的发生、发展、转移相关，可作为结直肠癌转移及预后监测的一项重要指标。