Gene expression profiles in esophageal adenocarcinoma predict survival after resection.
Gene expression profiles in esophageal adenocarcinoma predict survival after resection.
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食管腺癌的基因表达谱可预测切除后的生存率。
DOI：
10.1016/j.jtcvs.2012.10.031
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Luketich,JamesD
中科院分区：
文献类型：
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作者：
Pennathur,Arjun;Xi,Liqiang;Litle,VirginiaR;Gooding,WilliamE;Krasinskas,Alyssa;Landreneau,RodneyJ;Godfrey,TonyE;Luketich,JamesD
食管腺癌的发病率在西方人群中迅速增加。尽管积极治疗，食管切除术后的生存率是次优的。本研究的主要目的是评估食管腺癌的基因表达谱，并确定其与生存survival after surgery.METHODSWe进行了一项前瞻性的美国国立卫生研究院/美国国家癌症研究所资助的研究，以评估基因表达在食管腺癌患者接受食管切除术的预后意义。使用高通量寡核苷酸阵列分析肿瘤组织中的基因表达。使用尾强度统计和考克斯回归分析来分析基因表达与总生存期的关联。使用主成分的半监督方法构建基因签名。交叉验证的风险评分是通过进行10倍交叉验证，100倍。我们评估了64例食管腺癌患者接受食管切除术的基因表达。中位总生存期为27个月（95%置信区间为22至未达到）。过滤后，10，214个探针组用于存活分析。这些探针组的尾强度统计量（0.318）表明与总生存期显著相关。根据基因特征，患者被分为高风险组和低风险组。高风险患者的中位生存期为19个月，但低风险组的中位生存期未达到（P <0.05）。在多变量分析中，基因标记与生存率独立相关（风险比，2.22; P = 0.04）。此外，单个基因可以成功地组合成一个强预测性的，内部交叉验证的基因签名。如果进一步验证，这些结果可能有助于指导食管腺癌新辅助和辅助治疗的其他临床试验。
OBJECTIVEThe incidence of esophageal adenocarcinoma is rapidly increasing in the western population. Despite aggressive treatment, survival after esophagectomy is suboptimal. The main objective of the present study was to evaluate the gene expression profiles in esophageal adenocarcinoma and determine their association with survival after resection.METHODSWe conducted a prospective National Institutes of Health/National Cancer Institute funded study to evaluate the prognostic significance of gene expression in patients with esophageal adenocarcinoma undergoing esophagectomy. Gene expression in tumor tissue was analyzed using high-throughput oligonucleotide arrays. The association of gene expression and overall survival was analyzed using the tail-strength statistic and Cox regression analysis. Gene signatures were constructed with semisupervised methods using principal components. A cross-validated risk score was devised by conducting 10-fold cross-validation, 100 times.RESULTSWe evaluated the gene expression in 64 patients with esophageal adenocarcinoma who underwent esophagectomy. The median overall survival was 27 months (95% confidence interval 22 to not reached). After filtering, 10,214 probe sets were used for survival analysis. The tail-strength statistic for these probe sets (0.318) indicated a significant association with overall survival. Patients were classified into high- and low-risk groups, according to the gene signature. High-risk patients had a predicted median survival of 19 months, but the median was not reached for the low-risk group (P < .05). On multivariate analysis, the gene signature was independently associated with survival (hazard ratio, 2.22; P = .04).CONCLUSIONSGlobal gene expression levels were significantly associated with overall survival after esophagectomy. Furthermore, individual genes could be successfully combined into a strongly predictive, internally cross-validated gene signature. If validated further, these results could help direct additional clinical trials of neoadjuvant and adjuvant therapies for esophageal adenocarcinoma.