Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
Int J Oncol. 2022 Nov;61(5). doi: 10.3892/ijo.2022.5425. Epub 2022 Sep 21.
The tight‑junction protein claudin‑9 (CLDN9) is barely distributed in normal adult tissues but is ectopically expressed in various cancer types. Although multiple databases indicated upregulation of CLDN9 in endometrial cancers at the mRNA level, its protein expression and biological roles remain obscure. In the present study, the prognostic significance of CLDN9 expression in endometrial cancer was evaluated by immunohistochemical staining and semi‑quantification using formalin‑fixed paraffin‑embedded specimens obtained from 248 endometrial carcinoma cases. A total of 43 cases (17.3%) had high CLDN9 expression, whereas 205 cases (82.7%) exhibited low CLDN9 expression. The 5‑year disease‑specific survival rates in the high and low CLDN9 expression groups were 62.8 and 87.8% (P<0.001), respectively. In addition, multivariate analysis revealed that high CLDN9 expression was an independent prognostic factor (hazard ratio, 4.99; 95% CI, 1.96‑12.70; P<0.001). Furthermore, CLDN9 expression was significantly correlated with the expression of CLDN6 (P<0.001), which is the closest CLDN member to CLDN9 and a poor prognostic factor for endometrial carcinoma. The 5‑year disease‑specific survival rate of cases with CLDN6‑high/CLDN9‑high, CLDN6‑high/CLDN9‑low and CLDN6‑low/CLDN9‑high status was 30.0, 37.5 and 72.7%, respectively, whereas that of CLDN6‑low/CLDN9‑low was 89.8% (P=0.004). In conclusion, aberrant CLDN9 expression is a predictor of poor prognosis for endometrial cancer and may be utilized in combination with CLDN6 to achieve higher sensitivity.
紧密连接蛋白 9（CLDN9）在正常成人组织中几乎不分布，但在各种癌症类型中异位表达。尽管多个数据库表明 CLDN9 在子宫内膜癌中的 mRNA 水平上调，但它的蛋白表达和生物学作用仍然不清楚。在本研究中，通过免疫组织化学染色和半定量分析，使用 248 例子宫内膜癌病例的福尔马林固定石蜡包埋标本评估了 CLDN9 表达在子宫内膜癌中的预后意义。共有 43 例（17.3%）CLDN9 高表达，205 例（82.7%）CLDN9 低表达。高 CLDN9 表达组和低 CLDN9 表达组的 5 年疾病特异性生存率分别为 62.8%和 87.8%（P<0.001）。此外，多因素分析显示，高 CLDN9 表达是一个独立的预后因素（风险比，4.99；95%CI，1.96-12.70；P<0.001）。此外，CLDN9 表达与 CLDN6 的表达显著相关（P<0.001），CLDN6 是与 CLDN9 最接近的 CLDN 成员，也是子宫内膜癌的不良预后因素。CLDN6 高/CLDN9 高、CLDN6 高/CLDN9 低和 CLDN6 低/CLDN9 高状态病例的 5 年疾病特异性生存率分别为 30.0%、37.5%和 72.7%，而 CLDN6 低/CLDN9 低的生存率为 89.8%（P=0.004）。总之，异常的 CLDN9 表达是子宫内膜癌预后不良的预测因子，可能与 CLDN6 联合使用以提高敏感性。
