Iseki Yasuhito, Shibutani Masatsune, Maeda Kiyoshi, Nagahara Hisashi, Ikeya Tetsuro, Hirakawa Kosei
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
Oncol Lett. 2017 Jul;14(1):1025-1034. doi: 10.3892/ol.2017.6269. Epub 2017 May 26.
The loss of adhesion molecules is reported to be associated with tumor invasion and metastasis in numerous types of cancer. Epithelial (E)-cadherin is an important molecule for cell-to-cell adhesion, while cluster of differentiation (CD)44 is an important molecule for cell-to-extracellular matrix adhesion. The focus of the present study was to evaluate the significance of the expression of E-cadherin and CD44 in patients with the unresectable metastatic colorectal cancer (CRC) who are undergoing palliative chemotherapy. Formalin-fixed, paraffin-embedded samples were obtained from 49 patients who underwent primary tumor resection and who were receiving palliative chemotherapy for unresectable metastatic CRC. The expression of E-cadherin and CD44 was evaluated using immunohistochemistry. The expression of E-cadherin was not significantly associated with progression-free survival (PFS; P=0.2825) or overall survival (OS; P=0.6617). The expression of CD44 was not associated with PFS (P=0.4365), but it did exhibit a certain level of association with OS (P=0.0699). However, the combined low expression of E-cadherin and CD44 demonstrated a significant association with decreased PFS (P=0.0101) and OS (P=0.0009). The combined loss of E-cadherin and CD44 expression also led to a reduction in the objective response rate and disease control rate (P=0.0076 and P=0.0294, respectively). A univariate analysis indicated that the combined low expression of E-cadherin and CD44 (P=0.0474) and sex (P=0.0330) were significantly associated with decreased PFS, and multivariate analysis confirmed combined low expression of E-cadherin and CD44 as an independent risk factor for decreased PFS [hazard ratio (HR), 8.276; 95% confidence interval (CI), 1.383-43.311; P=0.0227]. Univariate and multivariate analyses also indicated that the combined low expression of E-cadherin and CD44 expression was a significant prognostic factor for poor OS (HR, 15.118; 95% CI, 2.645-77.490; P=0.0039). Therefore the current study suggests that the combined low expression of E-cadherin and CD44 is an effective independent predictor of decreased chemotherapeutic outcome and survival in patients with unresectable metastatic CRC.
据报道，在多种癌症类型中，黏附分子的缺失与肿瘤侵袭和转移相关。上皮（E）-钙黏蛋白是细胞间黏附的重要分子，而分化簇（CD）44是细胞与细胞外基质黏附的重要分子。本研究的重点是评估E-钙黏蛋白和CD44表达在接受姑息化疗的不可切除转移性结直肠癌（CRC）患者中的意义。从49例接受原发性肿瘤切除且因不可切除转移性CRC接受姑息化疗的患者中获取福尔马林固定、石蜡包埋的样本。使用免疫组织化学评估E-钙黏蛋白和CD44的表达。E-钙黏蛋白的表达与无进展生存期（PFS；P=0.2825）或总生存期（OS；P=0.6617）无显著相关性。CD44的表达与PFS无关（P=0.4365），但与OS有一定程度的相关性（P=0.0699）。然而，E-钙黏蛋白和CD44的联合低表达与PFS降低（P=0.0101）和OS降低（P=0.0009）显著相关。E-钙黏蛋白和CD44表达的联合缺失还导致客观缓解率和疾病控制率降低（分别为P=0.0076和P=0.0294）。单因素分析表明，E-钙黏蛋白和CD44的联合低表达（P=0.0474）和性别（P=0.0330）与PFS降低显著相关，多因素分析证实E-钙黏蛋白和CD44的联合低表达是PFS降低的独立危险因素[风险比（HR），8.276；95%置信区间（CI），1.383 - 43.311；P=0.0227]。单因素和多因素分析还表明，E-钙黏蛋白和CD44表达的联合低表达是OS不良的显著预后因素（HR，15.118；95%CI，2.645 - 77.490；P=0.0039）。因此，当前研究表明，E-钙黏蛋白和CD44的联合低表达是不可切除转移性CRC患者化疗疗效降低和生存期缩短的有效独立预测指标。
