RANTES expression is a predictor of survival in stage I lung adenocarcinoma.

RANTES expression is a predictor of survival in stage I lung adenocarcinoma.
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DOI：
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发表时间：
2002-12
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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通讯作者：
C. Moran;D. Arenberg;Chiang-Ching Huang;T. Giordano;Dafydd G. Thomas;David E. Misek;Guoan Chen;
C. Moran;D. Arenberg;Chiang-Ching Huang;T. Giordano;Dafydd G. Thomas;David E. Misek;Guoan Chen;
中科院分区：
其他
文献类型：
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作者：
C. Moran;D. Arenberg;Chiang-Ching Huang;T. Giordano;Dafydd G. Thomas;David E. Misek;Guoan Chen;

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目的在非小细胞肺癌(NSCLC)肿瘤中存在活跃的淋巴细胞反应(ALR)已被认为与较好的预后有关。本研究的目的是确定有ALR(ALR+)和没有ALR(ALR-)的I期非小细胞肺癌(ALR+)之间整体基因表达谱的差异。实验设计利用Affymetrix寡核苷酸芯片分析63例I期肺腺癌的基因表达。肿瘤被分成ALR+组和ALR-组，比较基因表达的统计学差异。用酶联免疫吸附试验和免疫组织化学方法对确定的候选基因进行了验证。这些患者的随访数据被收集并用于评估患者的预后。结果63例肿瘤中ALR阳性27例，ALR-36例。共有303个基因在两个群体之间有显著差异(t检验，P&lt；0.02)。ALR+肿瘤过表达的基因中有3个是趋化因子：小诱导细胞因子A4(MIP-1β)、RANTES和干扰素诱导蛋白10(IP-10)。免疫组织化学分析表明，肿瘤细胞表达这些细胞因子。ELISA法显示ALR+肿瘤在蛋白水平表达MIP-1β和RANTES。单因素COX比例风险分析显示RANTES是I期肺腺癌患者生存的预测因素(P=0.002)。结论经COX单因素比例风险模型检验，肺腺癌细胞RANTES表达是I期非小细胞肺癌患者生存的预测因素，可作为肺癌预后因素。
PURPOSE The presence of an active lymphocytic response (ALR) in non-small cell lung cancer (NSCLC) tumors has previously been associated with a more favorable prognosis. The purpose of this study was to identify differences in global gene expression profiles between stage I NSCLC tumors with ALR (ALR+) and those without ALR (ALR-). EXPERIMENTAL DESIGN Sixty-three stage I lung adenocarcinomas were analyzed for gene expression using Affymetrix oligonucleotide microarrays. Tumors were stratified into ALR+ and ALR- groups and compared for statistically significant differences in gene expression. Identified candidate genes were validated using both ELISA and immunohistochemistry. Follow-up data for these patients were collected and used to assess patient prognosis. RESULTS Of the 63 tumors studied, 27 were ALR+ and 36 were ALR-. A total of 303 genes showed significant differences in gene expression between the two populations (t test, P < 0.02). Three of the genes overexpressed by ALR+ tumors were the chemokines: small inducible cytokine A4 (MIP-1beta), RANTES, and interferon inducible protein 10 (IP-10). Immunohistochemistry analysis showed that the tumor cells expressed these cytokines. ELISA showed that MIP-1beta and RANTES were overexpressed at the protein level by ALR+ tumors. Univariate Cox proportional hazards analysis showed that RANTES was a predictor of survival in stage I lung adenocarcinomas (P = 0.002). CONCLUSION When tested in the Cox univariate proportional hazards model, RANTES expression by lung adenocarcinoma cells is a predictor of survival in stage I NSCLC patients and may be useful as a prognostic factor in lung cancer.