Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer
Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer
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DOI：
10.1007/s10120-019-01014-x
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发表时间：
2019-10-25
期刊：
影响因子：
7.4
通讯作者：
Imoto, Issei
中科院分区：
文献类型：
--
作者：
Kohmoto, Tomohiro;Masuda, Kiyoshi;Imoto, Issei
背景：我们的目标是寻找在胃癌中高表达的新的肿瘤促进因子，这些因子有助于恶化患者的预后。方法利用《癌症基因组图谱》和《基因表达总览》中的数据筛选胃癌中表达增强且与预后不良相关的基因。我们检测了胃癌组织中Claudin-6(CLDN6)的免疫反应性，以及CLDN6对胃癌细胞系细胞功能的影响。并对CLDN6促GC作用的机制进行了探讨。结果与癌旁非肿瘤组织相比，CLDN6基因在胃癌组织中高表达，且CLDN6的表达水平与胃癌患者，尤其是Lauren肠型胃癌患者的总体生存率呈正相关。此外，在肠型GC肿瘤中检测到的膜性CLDN6免疫反应与较差的总体生存相关。在表达CLDN6的GC细胞中，CLDN6的沉默抑制了细胞的增殖和迁移/侵袭能力，可能至少部分是通过抑制YAP1及其下游转录靶点的转录来实现的。结论本研究证实CLDN6是一种促进GC的基因，提示CLDN6可能是一种单一的预后标志物，并有望成为部分GC患者的治疗靶点。
Background We aimed to identify novel tumor-promoting drivers highly expressed in gastric cancer (GC) that contribute to worsened prognosis in affected patients. Methods Genes whose expression was increased and correlated with worse prognosis in GC were screened using datasets from the Cancer Genome Atlas and Gene Expression Omnibus. We examined Claudin-6 (CLDN6) immunoreactivity in GC tissues and the effect of CLDN6 on cellular functions in GC cell lines. The mechanisms underlying GC-promoting function of CLDN6 were also investigated. Results CLDN6 was identified as a gene overexpressed in GC tumors as compared with adjacent non-tumorous tissues and whose increased expression was positively correlated with worse overall survival of GC patients, particularly those with Lauren's intestinal type GC, in data from multiple publicly available datasets. Additionally, membranous CLDN6 immunoreactivity detected in intestinal type GC tumors was correlated with worse overall survival. In CLDN6-expressing GC cells, silencing of CLDN6 inhibited cell proliferation and migration/invasion abilities, possibly via suppressing transcription of YAP1 and its downstream transcriptional targets at least in part. Conclusions This study identified CLDN6 as a GC-promoting gene, suggesting that CLDN6 to be a possible single prognostic marker and promising therapeutic target for a subset of GC patients.