Aberrant Cadherin11 expression predicts distant metastasis of gastric cancer
Aberrant Cadherin11 expression predicts distant metastasis of gastric cancer
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DOI：
10.1016/j.prp.2022.154294
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发表时间：
2023-01-05
影响因子：
2.8
通讯作者：
Ishikawa, Shumpei
中科院分区：
文献类型：
--
作者：
Mita, Hideaki;Katoh, Hiroto;Ishikawa, Shumpei
胃癌（GC）的预后受远处转移和术后复发的显著影响。骨转移是胃癌预后最差的转移之一；然而，其分子机制和预测性生物标志物仍然难以捉摸。据报道，在前列腺癌和乳腺癌中，钙粘蛋白11 （CDH11）的过表达与骨转移有关。钙粘蛋白11是一种间充质细胞-细胞接触因子。CDH11 mRNA在大量GC组织中的过表达也被报道与较差的预后相关。然而，为了在CDH11与胃癌转移特征之间建立强有力的联系，需要更精确地评估CDH11在胃癌细胞中的表达。我们对342例胃癌患者的CDH11表达进行了免疫组织化学分析，其中标本是在手术时获得的，特别关注其在胃癌细胞中的异常膜表达。统计分析CDH11表达异常与胃癌远处转移及预后的关系。大约一半的胃癌病例在原发病变的胃癌细胞中显示CDH11的异常表达。CDH11异常表达与胃癌骨转移有统计学意义。此外，转移到肝脏和远处淋巴结也与CDH11表达有统计学相关性。原发性肿瘤病变中GC细胞中CDH11的异常表达被证明是胃癌远处转移的预测性生物标志物。表达CDH11的GCs需要预防性的临床关注，以检测转移性病变。
The prognosis of gastric cancer (GC) is significantly affected by distant metastases and postoperative recurrences. Bone metastasis is one of the worst prognostic metastases in GC; however, its molecular mechanisms and pre-dictive biomarkers remain elusive. In prostate and breast cancers, it has been reported that overexpression of Cadherin 11 (CDH11), a mesenchymal cell-cell contact factor, is known to be correlated with bone metastasis. Overexpression of CDH11 mRNA in bulk GC tissues has also been reported to be associated with a worse prognosis. However, a more precise evaluation of CDH11 expression in GC cells is necessary to establish a robust link between CDH11 and metastatic features of GC. We performed immunohistochemical analysis of CDH11 expression in 342 GC cases, of which specimens were obtained at the time of surgery, with a special focus on its aberrant membranous expression in GC cells. The correlations between aberrant CDH11 expression and distant metastases and the prognosis of GC cases were statistically investigated. Approximately half of the GC cases investigated showed aberrant expression of CDH11 in the GC cells of primary lesions. Aberrant CDH11 expression was statistically associated with bone metastasis of GCs. Moreover, metastases to the liver and distant lymph nodes were also statistically correlated with CDH11 expression. Aberrant CDH11 expression in GC cells in primary tumor lesions was shown to be a predictive biomarker of distant metastases in GC. GCs with CDH11 expression require preventive clinical attention for the detection of metastatic lesions.