Drg1 expression in 131 colorectal liver metastases:: Correlation with clinical variables and patient outcomes
Drg1 expression in 131 colorectal liver metastases:: Correlation with clinical variables and patient outcomes
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DOI：
10.1158/1078-0432.ccr-04-2417
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发表时间：
2005-05-01
影响因子：
11.5
通讯作者：
Schwartz, GK
中科院分区：
文献类型：
--
作者：
Shah, MA;Kemeny, N;Schwartz, GK
目的：分化相关基因1（DRG1）是近年来发现的一个在恶性肿瘤中表达下调的基因，被认为是大肠癌转移的抑制基因。它的表达与前列腺癌或乳腺癌患者的生存率提高有关。在临床前结直肠癌模型中，Drg1表达也与伊立替康治疗耐药相关。Drg1在结直肠癌中的临床评价有限。我们进行了这项研究，以评估Drg1在一个大型队列的转移性结直肠癌患者谁是irinotecan naive.Experimental设计的作用：我们研究了Drg1的表达免疫组化在131例转移性结直肠癌患者参加了一项临床试验的辅助氟尿嘧啶为基础的治疗，从1991年至1995年。我们相关的表达Drg1众多的临床和肿瘤相关的变量和患者的结果，包括一个子集的患者复发，并接受irinotecan为基础的therapy.Results：Drg1的表达被确定在所有转移性组织样本。有一个趋势，即高表达的Drg1（P = 0.07），并建议提高2年生存率（82.4%对69.6%，P = 0.148）的单叶转移。结论：在大肠癌中，Drg 1的高表达可能与大肠癌的侵袭性、惰性有关。高Drg1也可能与对伊立替康的相对耐药性相关。Drg1在恶性肿瘤中的作用仍有待确定。
Purpose: The differentiation-related gene-1 (Drg1) is a recently identified gene down-regulated in malignancy and a putative suppressor of colorectal cancer metastases. Its expression is associated with improved survival in patients with prostate or breast cancer. Drg1 expression is also associated with resistance to irinotecan therapy in preclinical colorectal cancer models. The clinical evaluation of Drg1 in colorectal cancer has been limited. We performed this study to evaluate the role of Drg1 in a large cohort of patients with metastatic colorectal cancer who were irinotecan naive.Experimental Design: We examined Drg1 expression by immunohistochemistry in 131 patients with metastatic colorectal cancer enrolled in a clinical trial of adjuvant fluorouracil-based therapy from 1991 to 1995. We correlated expression of Drg1 to numerous clinical and tumor related variables and to patient outcomes, including a subset of patients who recurred and received irinotecan-based therapy.Results: Drg1 expression was identified in all metastatic tissue samples. There was a trend for unilobar metastases with high Drg1 expression (P = 0.07) and a suggestion of improved 2-year survival (82.4% versus 69.6%, P = 0.148). High Drg1 expression suggested irinotecan resistance (P = 0.07).Conclusions: In colorectal cancer, Drg1 expression may be associated with a less aggressive, indolent colorectal cancer. High Drg1 may also be associated with relative resistance to irinotecan. The role of Drg1 in malignancy continues to be defined.