Clinical significance and biological role of L1 cell adhesion molecule in gastric cancer
Clinical significance and biological role of L1 cell adhesion molecule in gastric cancer
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DOI：
10.1038/s41416-019-0646-8
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发表时间：
2019-12-10
影响因子：
8.8
通讯作者：
Kusunoki, Masato
中科院分区：
文献类型：
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作者：
Ichikawa, Takashi;Okugawa, Yoshinaga;Kusunoki, Masato
背景技术背景：L1细胞粘附分子（L1 CAM）在恶性肿瘤中高度表达，可能在肿瘤进展中发挥关键作用。方法：我们通过免疫组化分析了309例胃癌患者福尔马林固定、石蜡包埋标本中L1 CAM蛋白的表达。我们进行了倾向评分匹配（PSM）分析，以阐明L1CAM对胃癌患者预后的影响。我们评估了另一组131例胃癌患者新鲜冷冻标本中L1CAM基因的表达，以确定其临床相关性。结果：L1CAM主要表达于胃癌组织中的肿瘤细胞，在胃癌组织中L1CAM的表达与胃癌组织中L1CAM的表达呈正相关。L1CAM表达升高是胃癌患者总生存期和无病生存期的独立预后因素，也是胃癌远处转移的独立危险因素。PSM分析显示L1CAM高表达与预后不良显著相关。使用新鲜冷冻标本的L1CAM基因表达在一个独立队列中成功验证了所有这些发现。抑制L1CAM可抑制胃癌细胞的增殖、周期进程、侵袭、迁移和抗失巢凋亡。结论：L1CAM可作为胃癌复发高危患者的一种生物学标志物。
BACKGROUND: L1 cell adhesion molecule (L1CAM) is highly expressed in malignant tumours and might play a pivotal role in tumour progression.METHODS: We analysed by immunohistochemistry L1CAM protein expression in formalin-fixed, paraffin-embedded specimens from 309 GC patients. We performed propensity score matching (PSM) analysis to clarify the prognostic impact of L1CAM in GC patients. We evaluated L1CAM gene expression in fresh frozen specimens from another group of 131 GC patients to establish its clinical relevance. The effects of changes in L1CAM were investigated in vitro and in vivo.RESULTS: L1CAM was mainly expressed in tumour cells of GC tissues. Elevated L1CAM expression was an independent prognostic factor for overall and disease-free survival, and an independent risk factor for distant metastasis in GC patients. PSM analysis showed that high L1CAM expression was significantly associated with poor prognosis. L1CAM gene expression using fresh frozen specimens successfully validated all of these findings in an independent cohort. Inhibition of L1CAM suppressed cell proliferation, cycle progress, invasion, migration and anoikis resistance in GC cells. Furthermore, L1CAM inhibition suppressed the growth of peritoneal metastasis.CONCLUSION: L1CAM may serve as a feasible biomarker for identification of patients who have a high risk of recurrence of GC.