Cha Eun Jung, Noh Sang Jae, Kwon Keun Sang, Kim Chan Young, Park Byung-Hyun, Park Ho Sung, Lee Ho, Chung Myoung Ja, Kang Myoung Jae, Lee Dong Geun, Moon Woo Sung, Jang Kyu Yun
Departments of Pathology, Research Institute of Clinical Medicine and Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
Clin Cancer Res. 2009 Jul 1;15(13):4453-9. doi: 10.1158/1078-0432.CCR-08-3329. Epub 2009 Jun 9.
SIRT1 (silent mating-type information regulation 2 homologue 1) expression has been reported to predict poor survival in some cancers. We therefore investigated the expression levels of SIRT1 and its negative regulator, DBC1 (deleted in breast cancer 1), in gastric cancer patients.
We evaluated immunohistochemical expression of DBC1, SIRT1, and p53 using 3-mm tumor cores from 177 gastric cancer patients for tissue microarray.
Positive expressions of DBC1 and SIRT1 were seen in 62% (109 of 177) and in 73% (130 of 177) of patients, respectively. Expression of DBC1 was significantly correlated with tumor stage (P = 0.007), lymph node metastasis (P < 0.001), tumor invasion (P = 0.001), venous invasion (P = 0.001), histologic types (P < 0.001), p53 expression (P < 0.001), and SIRT1 expression (P < 0.001). SIRT1 expression was also significantly correlated with tumor stage (P < 0.001), lymph node metastasis (P < 0.001), tumor invasion (P < 0.001), histologic types (P < 0.001), and p53 expression (P = 0.001). In addition, expression of DBC1 was significantly associated with shorter overall survival and relapse-free survival by univariate analysis (P < 0.001 and P < 0.001, respectively). SIRT1 expression was also significantly associated with shorter overall survival and relapse-free survival by univariate analysis (P = 0.001 and P = 0.001, respectively). Multivariate analysis showed that tumor stage and expression of DBC1 were independent prognostic factors significantly associated with overall survival and relapse-free survival.
This study shows that expression of DBC1 and SIRT1 is a significant prognostic indicator for gastric carcinoma patients.
据报道,沉默信息调节因子2同源物1(SIRT1)的表达可预测某些癌症患者的不良生存情况。因此,我们研究了胃癌患者中SIRT1及其负调节因子乳腺癌缺失基因1(DBC1)的表达水平。
我们使用来自177例胃癌患者的3毫米肿瘤组织芯构建组织芯片,评估DBC1、SIRT1和p53的免疫组化表达。
分别在62%(177例中的109例)和73%(177例中的130例)的患者中观察到DBC1和SIRT1的阳性表达。DBC1的表达与肿瘤分期(P = 0.007)、淋巴结转移(P < 0.001)、肿瘤浸润(P = 0.001)、静脉浸润(P = 0.001)、组织学类型(P < 0.001)、p53表达(P < 0.001)以及SIRT1表达(P < 0.001)显著相关。SIRT1的表达也与肿瘤分期(P < 0.001)、淋巴结转移(P < 0.001)、肿瘤浸润(P < 0.001)、组织学类型(P < 0.001)以及p53表达(P = 0.001)显著相关。此外,单因素分析显示DBC1的表达与较短的总生存期和无复发生存期显著相关(分别为P < 0.001和P < 0.001)。SIRT1的表达通过单因素分析也与较短的总生存期和无复发生存期显著相关(分别为P = 0.001和P = 0.001)。多因素分析表明,肿瘤分期和DBC1的表达是与总生存期和无复发生存期显著相关的独立预后因素。
本研究表明,DBC1和SIRT1的表达是胃癌患者的重要预后指标。