Overexpression of SPARC gene in human gastric carcinoma and its clinic-pathologic significance.
Overexpression of SPARC gene in human gastric carcinoma and its clinic-pathologic significance.
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DOI：
10.1038/sj.bjc.6602213
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发表时间：
2004-11-29
影响因子：
8.8
通讯作者：
Hsueh, S
中科院分区：
文献类型：
--
作者：
Wang, CS;Lin, KH;Chen, SL;Chan, YF;Hsueh, S
胃癌是世界上第二大常见癌症，也是台湾癌症相关死亡的第五大原因。为了提高胃癌患者的生存率，需要早期检测的生物标志物和有效的抗癌治疗。重要的第一步是分析胃癌中的基因表达并鉴定异常表达的基因，为此进行了 cDNA 微阵列。评估异常表达基因的临床病理相关性和预后意义，以确定胃癌的新生物标志物。 43 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的新鲜手术样本。在我们的微阵列结果中，酸性富含半胱氨酸分泌蛋白 (SPARC)（骨连接素）是肠癌和弥漫性胃癌中表达最高的基因之一，被选择进行进一步研究。使用实时定量逆转录聚合酶链反应 (Q-RT-PCR)、Northern 印迹和免疫组织化学染色验证 SPARC 的过度表达。与邻近非癌粘膜相比，肿瘤组织中 SPARC 的表达平均增加 4.27 倍 (95% CI 2.68–5.85) (P<0.001)。就壁浸润深度而言，与早期（T1）癌症相比，晚期（T2、T3和T4）癌症中SPARC的表达较高（P=0.048）。 SPARC高表达与淋巴结转移(P<0.001)、淋巴管侵犯(P=0.004)和神经周围侵犯(P=0.047)显着相关。 II期及以上患者SPARC表达显着高于I期患者（P=0.017）。 SPARC低表达患者的3年生存率明显好于高表达患者（logrank P=0.047）。这些数据表明 SPARC 作为胃癌预后标志物的潜力。
Gastric cancer is the second most common cancer in the world and the fifth leading cause of cancer-related death in Taiwan. To improve the survival of gastric cancer patients, biomarkers for early detection and effective anticancer therapy are required. An essential first step is to profile gene expression in gastric cancer and identify genes that are aberrantly expressed, and to do this cDNA microarrays were performed. The clinic–pathologic correlation and prognostic significance of the aberrantly expressed genes were evaluated to identify novel biomarkers of gastric cancer. Fresh surgical samples of tumour tissue and matching noncancerous mucosa were obtained immediately after gastric resection in 43 patients. Secreted Protein, Acidic and Rich in Cysteine (SPARC) (Osteonectins), one of the most highly expressed genes in both intestinal and diffuse gastric cancers in our microarray results, was selected for further study. The overexpression of SPARC was verified using real-time quantitative-reverse transcription–polymerase chain reaction (Q-RT–PCR), Northern blot and immunohistochemical staining. The expression of SPARC in tumour tissues was, on average, 4.27-fold increased (95% CI 2.68–5.85) compared to adjacent noncancerous mucosa (P<0.001). The expression of SPARC was higher in advanced (T2, T3 and T4) cancer compared to the early (T1) cancer (P=0.048) with regard to depth of wall invasion. Higher expression of SPARC was significantly associated with lymph node metastasis (P<0.001), lymphatic invasion (P=0.004) and perineural invasion (P=0.047). Expression of SPARC in patients in stage II and above was significantly higher than those in stage I (P=0.017). The 3-year survival of patients with lower expression of SPARC was significantly better than those with a higher expression (log rank P=0.047). These data indicate the potential of SPARC as a prognostic marker for gastric cancer.
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