Loss of E-cadherin independently predicts the lymph node status in colorectal cancer
Loss of E-cadherin independently predicts the lymph node status in colorectal cancer
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DOI：
10.1097/pat.0b013e3283425b7f
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发表时间：
2011-02-01
期刊：
影响因子：
4.5
通讯作者：
Lugli, A.
中科院分区：
文献类型：
--
作者：
Karamitopoulou, E.;Zlobec, I.;Lugli, A.
背景：识别生物标志物改善结直肠癌（CRC）患者的风险分层仍然是一个挑战。本研究的目的是确定独立的蛋白质标记物作为结直肠癌淋巴结（N）分期的预测因子。将来自221名CRC患者的肿瘤标本固定在多穿孔组织微阵列上，并评估21种肿瘤相关因子和一种参与CRC致癌作用的宿主相关因子，即β-连环蛋白、E-钙粘蛋白、EGFR、pERK、RHAMM、pAKT、pSMAD 2、p21、p16、BcI-2、Ki-67、APAF-1、MST 1、RKIP、VEGF、EphB 2、MMP 7、层粘连蛋白5 γ 2、MUC 1、CDX 2、半胱天冬酶-3以及肿瘤内和基质CD 8+肿瘤浸润淋巴细胞结果：淋巴结阳性的癌症显示p21的显著丢失（p = 0.026），BcI-2（p = 0.027），APAF-1（p = 0.033），EphB2（p = 0.006）、E-钙粘蛋白（p < 0.001）、RKIP（p = 0.019）、CD 8 + iTIL和sTIL（分别为p < 0.001和p = 0.008）和细胞质MST 1（p = 0.014）。基于受试者工作特征曲线下面积（AUC），EphB 2、E-cadherin、iTILs和sTILs被鉴定为N期的潜在预测因子（AUC值>0.6），但在多变量分析中只有E-cadherin的缺失是独立的预测因子。E-cadherin似乎是结直肠癌N期的一个强有力的预测因子，应在术前和术后考虑。结肠癌和直肠癌患者的手术治疗。
Background: The identification of biomarkers that improve risk stratification in patients with colorectal cancer (CRC) is still a challenge. The objective of our study was to identify independent protein markers as predictors of lymph node (N) stage in CRC.Methods: Tumour specimens from 221 CRC patients were mounted onto a multiple-punch tissue microarray and evaluated for 21 tumour related factors and one host related factor involved in CRC carcinogenesis, namely beta-catenin, E-cadherin, EGFR, pERK, RHAMM, pAKT, pSMAD2, p21, p16, BcI-2, Ki-67, APAF-1, MST1, RKIP, VEGF, EphB2, MMP7, Laminin5 gamma 2, MUC1, CDX2, caspase-3 as well as intra-tumoural and stromal CD8+ tumour infiltrating lymphocytes (iTILs and sTILs).Results: Node positive cancers showed significant losses for p21 (p = 0.026), BcI-2 (p = 0.027), APAF-1 (p = 0.033), EphB2 (p = 0.006), E-cadherin (p < 0.001), RKIP (p = 0.019), CD8+ iTILs and sTILs ( p < 0.001 and p = 0.008, respectively) and cytoplasmic MST1 (p = 0.014). Based on the area under the receiver operating characteristic curve (AUC) EphB2, E-cadherin, iTILs and sTILs were identified as potential predictors of N stage (AUC values >0.6), but only loss of E-cadherin was an independent predictor in multivariate analysis.Conclusions: E-cadherin appears to be a strong predictor of N stage in CRC and should be considered in pre-operative and post-operative management of colon and rectal cancer patients.