Loss of CEACAM1 is associated with poor prognosis and peritoneal dissemination of patients with gastric cancer.
Loss of CEACAM1 is associated with poor prognosis and peritoneal dissemination of patients with gastric cancer.
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CEACAM1 的缺失与胃癌患者的不良预后和腹膜播散有关。
DOI：
10.1038/s41598-019-49230-w
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Yamaue H.
中科院分区：
文献类型：
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作者：
Takeuchi A;Yokoyama S;Nakamori M;Nakamura M;Ojima T;Yamaguchi S;Mitani Y;Shively JE;Yamaue H.
CEACAM 1与多种癌症的恶性潜能相关。本研究旨在阐明癌胚抗原相关细胞粘附分子1（CEACAM 1）表达与胃癌恶性潜能之间的关系，并探讨CEACAM 1胞质结构域亚型平衡是否调节胃癌细胞的特性。对235例手术切除的胃癌患者进行CEACAM 1免疫组化分析。根据CEACAM 1在胃癌组织中的表达计算总生存率和腹膜转移的危险因素。将CEACAM 1长（CEACAM 1-L）或短（CEACAM 1-S）胞质亚型优势的患者与CEACAM 1无效表达的患者在总生存期方面进行比较。通过侵袭实验和三维培养检测CEACAM 1转染或敲低的胃癌细胞系NUGC 3和MKN 7，以阐明CEACAM 1是否调节胃癌细胞的侵袭、管腔形成和肿瘤生长。多因素分析表明，无CEACAM 1的胃癌是一个独立的预后因素和腹膜播散的危险因素。CEACAM 1-S优势型患者的预后优于CEACAM 1-L优势型患者。CEACAM 1 -4L过表达诱导NUGC 3细胞较少的侵袭，更多的管腔形成和较少的肿瘤生长。CEACAM 1 -4S过表达具有较少的侵袭性和较多的管腔形成，但不具有较少的肿瘤生长。CEACAM 1表达的敲低具有较少的侵袭性，但MKN 7细胞的管腔形成并没有减少。CEACAM 1缺失与胃癌患者预后不良和腹膜转移相关。CEACAM 1在胃癌细胞中的表达调节侵袭性、管腔形成和肿瘤生长。
CEACAM1 is associated with malignant potential of various cancers. The current study aims to clarify the association between carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression and malignant potential of gastric cancer and to address whether CEACAM1 cytoplasmic domain isoform balance modulates the properties of gastric cancer cells. Immunohistochemical analyses for CEACAM1 were performed in 235 patients with gastric cancer who underwent surgery. Risk factors for overall survival and peritoneal metastasis were calculated based on CEACAM1 expression in the gastric cancer tissue. Patients with CEACAM1 long (CEACAM1-L) or short (CEACAM1-S) cytoplasmic isoform dominance were compared with patients with null CEACAM1 expression in terms of overall survival. CEACAM1 transfected or knockdown gastric cancer cell line, NUGC3 and MKN7 cells, were examined by invasion assay and three dimensional (3D) culture, in order to clarify whether CEACAM1 modulate invasion, lumen formation and tumor growth of gastric cancer cells. Multivariate analysis demonstrated that gastric cancer without CEACAM1 is an independent prognostic factor and a risk factor for peritoneal dissemination. Patients with CEACAM1-S dominance had better prognosis than those with CEACAM1-L. CEACAM1-4L overexpression induced less invasion, more lumen formation, and less tumor growth of NUGC3 cells. CEACAM1-4S overexpression had less invasion and more lumen formations, but not less tumor growth. Knockdown of CEACAM1 expression had less invasion, but not less lumen formations of MKN7 cells. Loss of CEACAM1 is associated with poor prognosis and peritoneal dissemination of patients with gastric cancer. Expression of CEACAM1 in gastric cancer cells modulates invasiveness, lumen formation, and tumor growth.