Overexpression of a secretory leukocyte protease inhibitor in human gastric cancer

Overexpression of a secretory leukocyte protease inhibitor in human gastric cancer
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DOI:
10.1002/ijc.23746
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发表时间:
2008-10-15
影响因子:
6.4
通讯作者:
Lin, Kwang-Huei
Lin, Kwang-Huei
中科院分区:
医学1区
文献类型:
--
作者:
Cheng, Wan-Li;Wan, Chia-Siu;Lin, Kwang-Huei

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互补 DNA 微阵列已鉴定出胃癌患者中异常表达的基因。编码分泌性白细胞蛋白酶抑制剂(SLPI)的基因属于异常表达基因之一,与胃癌的转移相关。我们评估了 SLPI 表达作为检测胃癌的有用生物标志物的潜力。 60 名患者在胃切除术后立即获得肿瘤组织和匹配的非癌性粘膜。 SLPI 表达水平通过 Northern 和 Western blot 测试以及定量逆转录聚合酶链反应 (Q-RT-PCR) 测定。石蜡固定的肿瘤组织用于 119 例患者的免疫组织化学研究。除血浆 SLPI 外,所有检查均获得一致的结果。 SLPI mRNA 转录本和蛋白质在胃癌细胞中过度表达,并且与无浆膜(T1 和 T2)癌症相比,浆膜侵袭(T3 和 T4)癌症的壁浸润深度显着更大。这些增强的表达与淋巴结转移显着相关,并且在III期和IV期显着升高,并且高于I期和II期。 SLPI基因表达较低的患者的五年生存率明显好于表达较高的患者。为了更好地了解SLPI在人胃癌细胞中的功能,制备了同基因SLPI过表达细胞系(AZ521)。在SLPI过表达的细胞系中,迁移和侵袭能力分别增加了4.4倍至6.9倍,或3.0倍至4.1倍。结果表明 SLPI 是胃癌的潜在预后标志物及其在细胞侵袭中的功能。 (C) 2008 Wiley-I.iss, Inc.
Complementary DNA microarrays have identified aberrantly expressed genes in patients with gastric cancer. One that encodes secretory leukocyte protease inhibitor (SLPI) is among the aberrantly expressed genes and is associated with metastasis in gastric cancers. We evaluated the potential of SLPI expression as a helpful biomarker for detection of gastric cancer. Tumor tissue and matching noncancerous mucosa were obtained from 60 patients immediately after gastric resection. SLPI expression levels were determined by Northern and Western blot tests and quantitative-reverse transcriptase-polymerase chain reaction (Q-RT-PCR). Paraffin-fixed tumor tissues were used for immunohistochemistry study in 119 patients. A consistent result was obtained between all examinations except plasma SLPI. SLPI mRNA transcripts and protein were overexpressed in gastric cancer cells, and the depth of wall invasion was significantly greater in serosa-invading (T3 and T4) cancers compared to the serosa-free (T1 and T2) cancers. These enhanced expressions were significantly associated with lymph node metastasis, and were significantly higher in stages III and IV, and higher than those in stages I and II. Five-year survival of patients will lower expression of the SLPI gene was significantly better than among patients with a higher expression. To better understand the function of SLPI in human gastric cancer cells, isogenic SLPI overexpressing cell lines (AZ521) were prepared. The migratory and invasive abilities were increased 4.4-fold to 6.9-fold, or 3.0-fold to 4.1-fold, respectively, in SLPI-overexpressing cell lines. The results point to SLPI as a potential prognostic marker for gastric cancer and its function in cell invasion. (C) 2008 Wiley-I.iss, Inc.