利用大肠杆菌氨苄青霉素分泌陷阱（CAST）方法鉴定硬癌型胃癌中的新型跨膜蛋白：TM9SF3 参与肿瘤侵袭并作为预后因素。
Identification of novel transmembrane proteins in scirrhous-type gastric cancer by the Escherichia coli ampicillin secretion trap (CAST) method: TM9SF3 participates in tumor invasion and serves as a prognostic factor.
机构信息
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
出版信息
Pathobiology. 2014;81(3):138-48. doi: 10.1159/000357821. Epub 2014 Mar 8.
OBJECTIVE
Scirrhous-type gastric cancer (GC) is highly aggressive and has a poor prognosis due to rapid cancer cell infiltration accompanied by extensive stromal fibrosis. The aim of this study is to identify genes that encode transmembrane proteins frequently expressed in scirrhous-type GC.
METHODS
We compared Escherichia coli ampicillin secretion trap (CAST) libraries from 2 human scirrhous-type GC tissues with a normal stomach CAST library. By sequencing 2,880 colonies from scirrhous CAST libraries, we identified a list of candidate genes.
RESULTS
We focused on the TM9SF3 gene because it has the highest clone count, and immunohistochemical analysis demonstrated that 46 (50%) of 91 GC cases were positive for TM9SF3, which was observed frequently in scirrhous-type GC. TM9SF3 expression showed a significant correlation with the depth of invasion, tumor stage and undifferentiated GC. There was a strong correlation between TM9SF3 expression and poor patient outcome, which was validated in two separate cohorts by immunostaining and quantitative RT-PCR, respectively. Transient knockdown of the TM9SF3 gene by siRNA showed decreased tumor cell-invasive capacity.
CONCLUSION
Our results indicate that TM9SF3 might be a potential diagnostic and therapeutic target for scirrhous-type GC.
目的
硬癌型胃癌（GC）由于癌细胞快速浸润并伴有广泛的基质纤维化，侵袭性强，预后差。本研究旨在鉴定在硬癌型 GC 中频繁表达的跨膜蛋白编码基因。
方法
我们将 2 个人类硬癌型 GC 组织的大肠杆菌氨苄青霉素分泌陷阱（CAST）文库与正常胃 CAST 文库进行比较。通过对 2880 个硬癌 CAST 文库克隆进行测序，我们确定了一组候选基因。
结果
我们重点关注 TM9SF3 基因，因为它的克隆计数最高，免疫组织化学分析表明，91 例 GC 病例中有 46 例（50%）TM9SF3 阳性，在硬癌型 GC 中观察到 TM9SF3 表达频繁。TM9SF3 表达与浸润深度、肿瘤分期和未分化 GC 显著相关。通过免疫染色和定量 RT-PCR 分别在两个独立的队列中验证了 TM9SF3 表达与患者预后不良之间存在很强的相关性。TM9SF3 基因的瞬时敲低通过 siRNA 显示出肿瘤细胞侵袭能力的降低。
结论
我们的结果表明，TM9SF3 可能是硬癌型 GC 的潜在诊断和治疗靶点。
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