人再生基因蛋白Ⅳ和细胞角蛋白18在胃癌患者血清中的表达及临床意义

Regenerating gene type Ⅳ and cytokeratin 18 in the patients with advanced gastric cancer: expression and clinical significance

目的探讨人再生基因蛋白Ⅳ（REGⅣ）和细胞角蛋白18（CK18）在胃癌患者血清中的表达及其在疗效监测中的应用价值。方法收集2008年5月-2010年7月在北京肿瘤医院消化肿瘤内科接受化疗的61例晚期胃腺癌患者及32例同期健康成年人的血清标本，采用ELISA法检测胃癌患者化疗前后以及健康对照者的血清REGIV、CK1871水平。所有化疗均为一线治疗，方案以氟尿嘧啶类药物为基础，联合铂类（顺铂或奥沙利铂）加或不加紫杉类的三药或两药联合方案，根据RECIST1．0标准行疗效评价，分为完全缓解（CR）、部分缓解（vR）、稳定（SD）和进展（VD）。结果胃癌组血清REGIV和CK18水平显著高于对照组[P〈0．01，REGIV5．15（2．14—22．55）ng／mlvs2．22（0．02～12．29）ng／ml，CK-18132．29（24．97～473．62）U／Lvs63．05（16．06—294．58）U／L]。在胃癌患者中，有淋巴结转移者的REGⅣ和CK18水平高于无淋巴结转移者（p〈0．05）。61例胃癌患者中，26例对化疗敏感（CR＋PR），35例不敏感（SD＋PD），这两类患者化疗前的REGIV、CK18表达水平差异无统计学意义（P〉0．05）。36例有化疗前后配对血清标本的患者中，CR＋PR患者14例，sD16例，PD6N，各类患者的REGIV、CK18表达水平在化疗前后差异无统计学意义（p〉0．05）。结论REGIV和CK18作为血清标志物对胃癌有一定诊断价值，但两者化疗前水平及化疗前后变化与晚期胃癌疗效无明显相关性。

Objective To explore the expression of two serum markers, namely regenerating gene type Ⅳ （REG Ⅳ, also named ＂regenerating islet-derived family, member 4＂） and cytokeratin 18 （CK18）, and evaluate the correlation between REG IV and CK18, and their value in monitoring the effect of chemotherapy in patients with advanced gastric cancer. Methods As a retrospective study, the in-patients with advanced gastric cancer treated at the gastrointestinal medical department of Beijing Cancer Hospital and a cohort of healthy individuals were included. Peripheral venous blood was collected, and ELISA quantitative analysis was used to determine the serum levels of REG IV and CK18 in patients with gastric cancer before and after chemotherapy and also healthy controls. Results Compared with healthy control individuals （n=32）, patients with gastric cancer （n=61） showed significantly （P〈0.01） increased KEG IV and CK-18 levels in the serum （REG Ⅳ 2.51 ± 1.96ng/ml versus 6.50 ± 4.36ng/ml; CK-18 69.13 ± 45.61U/L versus 141.00±71.26U/L）. Compared with those patients without lymphnodes metastasis, patients with positive lymphnodes metastasis showed significantly increased REG IV and CK-18 levels in the serum （P〈0.05）, indicating there was a correlation between KEG IV and CK18 levels and lymphnodes metastasis. The therapeutic response to the combined chemotherapy in a total of 61 gastric cancer patients was as follows： 26 patients showed chemotherapy sensitive （CR＋PR）, and 35 patients were non-sensitive （SD＋PD）. No correlation was found between REG IV and CK18 levels and response to chemotherapy in both groups （P〉0.05）. The response to the combined chemotherapy among 36 patients who had matched serum for examination after chemotherapy was as follows： 14 patients were in chemotherapy-sensitive group （CR＋PR）, 16 patients with stable disease （SD）, and 6 patients showed progressive disease （PD）. There was no change in KEG Ⅳ and CK18 before and after chemotherapy for predicting the outcome of the patients （P〉0.05）. Conclusion Compared with healthy control individuals, patients with gastric cancer showed significantly increased REG IV and CK-18 levels in the serum. No association was found between REG Ⅳ and CK18 levels and response to chemotherapy. Changes in REG IV and CK18 before or after chemotherapy were not found significant in predicting the treatment result of the patients.