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下调的 SPARCL1 与人胃癌的临床意义相关。

Down-regulated SPARCL1 is associated with clinical significance in human gastric cancer.

机构信息

Department of Medical Oncology, Changzheng Hospital, Shanghai, People's Republic of China.

出版信息

J Surg Oncol. 2012 Jan;105(1):31-7. doi: 10.1002/jso.22025. Epub 2011 Aug 30.

Abstract

BACKGROUND

SPARC-like protein 1 (SPARCL1), a member of extracelluar matrix glycoprotein, is involved in many physiological functions.

METHODS

Tissue microarray (TMA) blocks were constructed based on 1,072 Chinese patients, containing both gastric cancer (GC) tissues and adjacent normal mucosa tissues. We analyzed the expression of SPARCL1 from both mRNA and protein level, using Real-time quantitative polymerase chain reaction (qRT-PCR), semi-quantitative PCR, immunohistochemistry (IHC), and Western blotting. Loss of heterozygosity analysis at the SPARCL1 gene locus was carried out using ten paired tumor and matched normal tissues.

RESULTS

SPARCL1 mRNA was significantly reduced in tumor specimens compared with normal tissues. Down-regulation of SPARCL1 protein was detected in 413 cases (38.7%) of 1,072 primary gastric tumor tissues. Kaplan-Meier survival curves demonstrated that SPARCL1-positive patients had better median survival time than SPARCL1-negative patients (59 months vs. 28 months, P = 0.001). Multivariate survival analysis revealed that SPARCL1 was an independent prognostic factor in gastric adenocarcinoma patients with no metastasis and well/moderately differentiated. The incidence of LOH for each individual marker was 12.5% (1/8) for D4S2462, 20% (2/10) for D4S2929, and 33.3% (3/9) for SPARCL1.

CONCLUSIONS

Our study revealed the clinical significance of SPARCL1 expression, providing a basis that the loss of SPARCL1 is a negative event in GC progression and prognosis. Furthermore, SPARCL1 protein might be considered to be a potential differentiation marker.

摘要

背景

富含半胱氨酸的酸性分泌蛋白 1(SPARC-like protein 1,SPARCL1)是细胞外基质糖蛋白的一个成员,参与了许多生理功能。

方法

基于 1072 例中国患者构建组织微阵列(TMA)块,其中包含胃癌(GC)组织和相邻正常黏膜组织。我们使用实时定量聚合酶链反应(qRT-PCR)、半定量 PCR、免疫组织化学(IHC)和 Western blot 分析了 SPARCL1 的表达水平。使用十对肿瘤和匹配的正常组织进行了 SPARCL1 基因座的杂合性丢失分析。

结果

与正常组织相比,肿瘤标本中的 SPARCL1mRNA 显著降低。在 1072 例原发性胃癌组织中,有 413 例(38.7%)检测到 SPARCL1 蛋白下调。Kaplan-Meier 生存曲线表明,SPARCL1 阳性患者的中位生存时间优于 SPARCL1 阴性患者(59 个月 vs. 28 个月,P = 0.001)。多因素生存分析显示,SPARCL1 是无转移和高/中分化的胃腺癌患者的独立预后因素。每个个体标记物的 LOH 发生率为 D4S2462(1/8)为 12.5%,D4S2929(2/10)为 20%,SPARCL1(3/9)为 33.3%。

结论

本研究揭示了 SPARCL1 表达的临床意义,为 SPARCL1 的缺失是 GC 进展和预后的负性事件提供了依据。此外,SPARCL1 蛋白可能被视为一种潜在的分化标志物。

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