Prognostic significance of osteopontin expression in human gastric carcinoma
Prognostic significance of osteopontin expression in human gastric carcinoma
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DOI：
10.1245/s10434-007-9564-8
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发表时间：
2007-12-01
影响因子：
3.7
通讯作者：
Shimada, Yutaka
中科院分区：
文献类型：
--
作者：
Higashiyama, Motoshige;Ito, Tetsuo;Shimada, Yutaka
背景：骨桥蛋白（OPN）是一种分泌型整合素结合糖磷蛋白，与多种实体瘤的发生发展有关。为探讨骨桥蛋白（OPN）在胃癌中的临床意义，我们采用免疫印迹法检测了胃癌组织中OPN的表达。采用半定量逆转录聚合酶链反应（RT-PCR）方法，对18例胃癌组织和相应正常胃粘膜组织中骨桥蛋白（OPN）mRNA的表达进行了比较。结果：4种胃癌细胞系的OPN蛋白表达水平与阳性对照（HeLa细胞）几乎相同。OPN mRNA在83%（15/18）的肿瘤中表达上调。在免疫组化染色中，90个肿瘤被分类为阴性（-），而205个被分类为阳性（1+，2+或3+）。OPN蛋白表达水平与患者的年龄（p = 0.04）、肿瘤深度（p = 0.03）、组织学分级（p = 0.008）和血行转移（p = 0.007）显著相关。Kaplan-Meier分析显示OPN阳性与较短的生存时间显著相关（p = 0.027）。多因素分析显示，OPN阳性是胃癌血行转移的独立危险因素（p = 0.034）。结论：OPN表达增加是胃癌患者生存期缩短的重要决定因素，OPN阳性可能有助于预测胃癌血行转移的风险。
Background: Osteopontin (OPN) is a secreted, integrin-binding glycophosphoprotein that has been implicated in the progression of various solid tumors. To evaluate the clinical significance of OPN in gastric carcinoma, we investigated OPN expression in resected tumors.Methods: Expression of OPN protein by gastric cancer cells was evaluated using western blot analysis. OPN messenger RNA (mRNA) expression in 18 gastric cancers was compared with that in the corresponding normal gastric epithelium by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Paraffin sections of tumors from 295 patients with gastric cancer were also investigated using immunohistochemistry.Results: All four gastric cancer cell lines analyzed using western blotting had almost the same level of OPN protein expression as the positive control (HeLa cells). OPN mRNA was upregulated in 83% (15/18) of the tumors studied. On immunohistochemical staining, 90 tumors were classified as negative (-), whereas 205 were classified as positive (1+, 2+, or 3+). The level of OPN protein expression was significantly associated with the patient's age (p = 0.04), tumor depth (p = 0.03), histological grade (p = 0.008), and hematogenous metastasis (p = 0.007). Kaplan-Meier analysis showed that OPN positivity was significantly associated with a shorter survival time (p = 0.027). Furthermore, multivariate analysis revealed that OPN positivity was an independent risk factor for hematogenous metastasis (p = 0.034).Conclusions: The present findings suggest that increased tumor expression of OPN is an important determinant of shorter survival time and that OPN positivity may be useful for predicting the risk of hematogenous metastasis in gastric cancer patients.