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淋巴管浸润与胃癌患者的不良生存相关:基因表达与组织芯片技术的应用

Lymphovascular invasion is associated with poor survival in gastric cancer: an application of gene-expression and tissue array techniques.

作者信息

Dicken Bryan J, Graham Kathryn, Hamilton Stewart M, Andrews Sam, Lai Raymond, Listgarten Jennifer, Jhangri Gian S, Saunders L Duncan, Damaraju Sambasivarao, Cass Carol

机构信息

Department of Surgery, University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada.

出版信息

Ann Surg. 2006 Jan;243(1):64-73. doi: 10.1097/01.sla.0000194087.96582.3e.

Abstract

OBJECTIVES

To examine a population-based cohort for the association between clinicopathologic predictors of survival and immunohistochemical markers (IHC), and to assess changes in gene expression that are associated with lymphovascular invasion (LVI).

SUMMARY BACKGROUND DATA

LVI has been associated with poor survival and aggressive tumor behavior. The molecular changes responsible for the behavior of gastric cancer have yet to be determined. Characterization of IHC markers and gene expression profiles may identify molecular alterations governing tumor behavior.

METHODS

: Clinicopathologic and survival data of 114 patients were reviewed. Archival specimens were used to construct a multitumor tissue array that was subjected to IHC of selected protein targets. Correlation of IHC with tumor thickness (T status), LVI and prognosis was studied. Microarray analysis of fresh gastric cancer tissue was conducted to examine the gene expression profile with respect to LVI.

RESULTS

In a multivariate analysis, nodal status (N), metastasis (M), and LVI were independent predictors of survival. LVI was associated with a 5-year survival of 13.9% versus 55.9% in patients in whom it was absent. LVI correlated with advancing T status (P = 0.001) and N status (P < 0.001). IHC staining of cyclooxygenase-2 (COX-2) correlated with T status, tumor grade, lymph node positivity, and IHC staining of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Microarray analyses suggested differential expression of oligophrenin-1 (OPHN1) and ribophorin-II (RPNII) with respect to LVI.

CONCLUSION

LVI was an independent predictor of survival in gastric cancer. Expression of COX-2 may facilitate tumor invasion through MMP-2 and MMP-9 activation. OPHN1 and RPN II appeared to be differentially expressed in gastric cancers exhibiting LVI. The reported function of OPHN1 and RPN II makes these gene products promising candidates for future studies involving LVI in gastric cancer.

摘要

目的

在一个基于人群的队列中研究生存的临床病理预测因素与免疫组化标志物(IHC)之间的关联,并评估与淋巴管侵犯(LVI)相关的基因表达变化。

总结背景数据

LVI与生存不良和侵袭性肿瘤行为相关。导致胃癌行为的分子变化尚未确定。免疫组化标志物和基因表达谱的特征分析可能会识别出控制肿瘤行为的分子改变。

方法

回顾了114例患者的临床病理和生存数据。利用存档标本构建多肿瘤组织芯片,并对选定的蛋白质靶点进行免疫组化。研究免疫组化与肿瘤厚度(T分期)、LVI及预后的相关性。对新鲜胃癌组织进行微阵列分析,以研究与LVI相关的基因表达谱。

结果

在多变量分析中,淋巴结状态(N)、转移(M)和LVI是生存的独立预测因素。LVI患者的5年生存率为13.9%,而无LVI患者为55.9%。LVI与T分期进展(P = 0.001)和N分期(P < 0.001)相关。环氧合酶-2(COX-2)的免疫组化染色与T分期、肿瘤分级、淋巴结阳性以及基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的免疫组化染色相关。微阵列分析提示少突素-1(OPHN1)和核糖体结合蛋白-II(RPNII)在LVI方面存在差异表达。

结论

LVI是胃癌生存的独立预测因素。COX-2的表达可能通过激活MMP-2和MMP-9促进肿瘤侵袭。OPHN1和RPN II在表现出LVI的胃癌中似乎存在差异表达。OPHN1和RPN II的已知功能使这些基因产物成为未来胃癌LVI相关研究的有前景的候选对象。

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