Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation.
Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation.
复制标题
组合的秘密组学和转录组学揭示了癌症衍生的GDF15参与弥漫型胃癌进展和成纤维细胞激活。
DOI：
10.1038/srep21681
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发表时间：
2016-02-19
影响因子：
4.6
通讯作者：
Nomura F
中科院分区：
文献类型：
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作者：
Ishige T;Nishimura M;Satoh M;Fujimoto M;Fukuyo M;Semba T;Kado S;Tsuchida S;Sawai S;Matsushita K;Togawa A;Matsubara H;Kaneda A;Nomura F
胃癌分为两种亚型，弥漫性和肠性。弥漫性胃癌（DGC）预后较差，其分子病理尚不完全清楚。本研究的目的是确定参与DGC进展的功能分泌分子。我们将六种胃癌细胞系的分泌组学和胃癌组织的基因表达分析与公开的微阵列数据相结合。分层聚类揭示了弥漫性肠型和肠型之间的特征基因表达差异。由于GDF15仅在胎儿组织中高表达，因此被选为功能性分泌分子。GDF15蛋白在DGC细胞系和组织中表达较高。DGC患者血清GDF15水平明显高于健康人及慢性胃炎患者，且与肠壁侵袭及淋巴结转移呈正相关。此外，GDF15刺激NIH3T3成纤维细胞可增强细胞增殖，上调细胞外基质基因表达，与TGF-β刺激相似。这些结果表明GDF15有助于成纤维细胞的激活。综上所述，本研究揭示GDF15可能是DGC进展的一种新的功能性分泌分子，可能通过影响成纤维细胞功能以及TGF-β在癌症进展中发挥重要作用。
Gastric cancer is classified into two subtypes, diffuse and intestinal. The diffuse-type gastric cancer (DGC) has poorer prognosis, and the molecular pathology is not yet fully understood. The purpose of this study was to identify functional secreted molecules involved in DGC progression. We integrated the secretomics of six gastric cancer cell lines and gene expression analysis of gastric cancer tissues with publicly available microarray data. Hierarchical clustering revealed characteristic gene expression differences between diffuse- and intestinal-types. GDF15 was selected as a functional secreted molecule owing to high expression only in fetal tissues. Protein expression of GDF15 was higher in DGC cell lines and tissues. Serum levels of GDF15 were significant higher in DGC patients as compared with healthy individuals and chronic gastritis patients, and positively correlated with wall invasion and lymph node metastasis. In addition, the stimulation of GDF15 on NIH3T3 fibroblast enhanced proliferation and up-regulated expression of extracellular matrix genes, which were similar to TGF-β stimulation. These results indicate that GDF15 contributes to fibroblast activation. In conclusion, this study revealed that GDF15 may be a novel functional secreted molecule for DGC progression, possibly having important roles for cancer progression via the affecting fibroblast function, as well as TGF-β.