Integrated expression profiling of potassium channels identifys KCNN4 as a prognostic biomarker of pancreatic cancer
Integrated expression profiling of potassium channels identifys KCNN4 as a prognostic biomarker of pancreatic cancer
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钾通道的整合表达谱将 KCNN4 确定为胰腺癌的预后生物标志物
DOI：
10.1016/j.bbrc.2017.10.072
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发表时间：
2017-12-09
影响因子：
3.1
通讯作者：
Zhang, Zhigang
中科院分区：
文献类型：
--
作者：
Jiang, Shuheng;Zhu, Lili;Zhang, Zhigang
钾（K+）通道失调以前已被证明会促进许多类型癌症的发展和进展。同时，经络在调节胰腺内分泌和外分泌功能方面也尤为重要。然而，K+通道在胰腺导管腺癌（PDAC）中的表达模式和预后意义尚不清楚。在这项研究中，通过筛选包含36个显微切割的PDAC和匹配的正常胰腺组织样本的GEO数据集，在PDAC中鉴定出4个差异表达的K+通道（KCNJ 5，KCNJ 16，KCNN 4和KCNK 1）。通过免疫组织化学分析来自bar re下的Pdx 1-（C）、bar ras下的LSL-（K）（G12 D/+）小鼠（KC）、bar re下的Pdx 1-（C）、bar ras下的LSL-（K）（G12 D/+）小鼠（KC）的组织切片; LSL-Tr（P）低于bar 53（R172 H/+）小鼠（KPC）和人PDAC组织微阵列，我们发现，与未转化的胰腺组织相比，胰腺上皮内瘤变（PanIN）和PDAC上皮细胞中钙激活的K+通道KCNN 4显著升高。上皮KCNN 4高表达与晚期TNM分期密切相关，并预示PDAC患者预后不良。在单变量和多变量分析中，KCNN 4表达升高与生存期缩短显著相关。总之，PDAC及其前体PanIN中K+通道表达模式的鉴定证明了KCNN 4通道在PDAC恶性转化过程中的重要性。基于两个独立队列的预后信号，KCNN 4应被视为有希望的治疗靶点。(C)2017爱思唯尔公司All rights reserved.
Dysregulated potassium (K+) channels have previously been shown to promote the development and progression of many types of cancers. Meanwhile, channels are particularly important in regulating the endocrine and exocrine functions of pancreas. However, the expression pattern and prognostic significance of K+ channels in pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this study, by screening a GEO dataset containing 36 microdissected PDAC and matching normal pancreatic tissue samples, four differentially expressed K+ channels (KCNJ5, KCNJ16, KCNN4 and KCNK1) were identified in PDAC. by immunohistochemical analysis of tissue sections from Pdx1-(C) under bar re; LSL-(K) under bar ras(G12D /+) mice (KC), Pdx1-(C) under bar re; LSL-(K) under bar ras(G12D/+); LSL-Tr (P) under bar 53(R172H/+) mice (KPC) and human PDAC tissue microarrays, we found that Ca2+-activated K+ channel KCNN4 was significantly elevated in pancreatic intraepithelial neoplasia (PanIN) and PDAC epithelia compared with untransformed pancreas tissues. Higher epithelial KCNN4 expression was closely correlated with advanced TNM stages and predicted a poor prognosis in patients with PDAC. Elevated KCNN4 expression was significantly associated with shorter survival in univariable and multivariable analyses. Collectively, the identification of expression pattern of K+ channels in PDAC and its precursor PanIN demonstrates the importance of KCNN4 channel during the malignant transformation of PDAC. On the basis of the prognostic signals from two independent cohorts, KCNN4 should be considered as a promising therapeutic target. (C) 2017 Elsevier Inc. All rights reserved.