Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, KhonKaen University, Khon Kaen 40002, Thailand.
National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani 12120, Thailand.
Molecules. 2021 May 22;26(11):3105. doi: 10.3390/molecules26113105.
Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes. Currently, the treatment and prognosis for CCA are mostly poor. Recently, we have reported that coiled-coil domain containing 25 (CCDC25) protein level in the sera may be a diagnostic marker for CCA. Subsequently, we identified three binding proteins of CCDC25 and found that kallikrein-11 (KLK11) expression was highest among those binding proteins. In this study, we investigated CCDC25 and KLK11 expression in CCA and adjacent normal tissues ( = 18) using immunohistochemistry. The results demonstrated that the expressions of CCDC25 and KLK11 in CCA tissues were both significantly higher than the adjacent tissues ( < 0.001 and = 0.001, respectively). Then, using GEPIA bioinformatics analysis, KLK11 mRNA was significantly overexpressed in CCA tumor tissues compared with normal tissues ( < 0.05). Moreover, CCDC25 expression was positively correlated with KLK11 expression in CCA with lymph node metastasis ( = 0.028, r = 0.593). An analysis for the interaction of KLK11 with CCDC25 and other proteins, using STRING version 11.0, revealed that CCDC25 and KLK11 correlated with metastasis-related proteins. In addition, Kaplan-Meier survival curve analysis revealed that a high expression of KLK11 was associated with the poor prognosis of CCA. In conclusion, KLK11 is, as a binding protein for CCDC25, possibly involved in the metastatic process of CCA. KLK11 may be used as a prognostic marker for CCA.
胆管癌（CCA）是一种来源于胆管细胞的恶性肿瘤。目前，CCA 的治疗和预后大多较差。最近，我们报道了血清中卷曲螺旋结构域蛋白 25（CCDC25）蛋白水平可能是 CCA 的诊断标志物。随后，我们鉴定了 CCDC25 的三个结合蛋白，发现其中 KLK11 表达最高。在这项研究中，我们使用免疫组织化学法检测了 18 例 CCA 及其相邻正常组织中 CCDC25 和 KLK11 的表达。结果表明，CCA 组织中 CCDC25 和 KLK11 的表达均明显高于相邻组织（<0.001 和=0.001）。然后，使用 GEPIA 生物信息学分析，与正常组织相比，CCA 肿瘤组织中 KLK11mRNA 明显过表达（<0.05）。此外，在有淋巴结转移的 CCA 中，CCDC25 的表达与 KLK11 的表达呈正相关（=0.028，r=0.593）。使用 STRING 版本 11.0 对 KLK11 与 CCDC25 和其他蛋白的相互作用进行分析，结果显示 CCDC25 和 KLK11 与转移相关蛋白相关。此外，Kaplan-Meier 生存曲线分析显示，KLK11 高表达与 CCA 的不良预后相关。综上所述，KLK11 作为 CCDC25 的结合蛋白，可能参与 CCA 的转移过程。KLK11 可能可作为 CCA 的预后标志物。
