A genomewide transcriptomic approach identifies a novel gene expression signature for the detection of lymph node metastasis in patients with early stage gastric cancer
A genomewide transcriptomic approach identifies a novel gene expression signature for the detection of lymph node metastasis in patients with early stage gastric cancer
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DOI：
10.1016/j.ebiom.2019.01.057
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发表时间：
2019-03-01
期刊：
影响因子：
11.1
通讯作者：
Goel, Ajay
中科院分区：
文献类型：
--
作者：
Izumi, Daisuke;Gao, Feng;Goel, Ajay
背景资料：虽然识别淋巴结（LN）转移是一个公认的策略，以改善胃癌（GC）患者的结果，目前缺乏足够的分子生物标志物，可以识别这种转移的可用性。在此，我们已经开发了一个强大的基因表达签名检测LN转移早期GC通过使用转录组范围内的生物标志物的发现和随后的验证在多个clinical cohols.Methods：共532例病理T1和T2 GC从4个不同的队列进行了分析。使用两个独立的数据集（n= 96和n= 188）来建立用于鉴定GC患者中的LN转移的基因签名。我们的基因表达特征的诊断性能随后在两个独立的临床队列中使用qRT-PCR测定进行评估（n= 101和n= 147），并随后与传统的肿瘤标志物和基于图像的诊断进行比较。我们通过分析多个高通量数据集建立了一个15个基因的签名，该签名在两个训练中都能稳健地区分LN状态。（AUC= 0.765，95% CI 0.667-0.863）和验证队列（AUC= 0.742，95% CI 0.630-0.852）。值得注意的是，与常规肿瘤标志物CEA相比，15基因标记显著上级。（P= 0.04）和CA 19 -9（P=.005），以及基于计算机断层扫描的成像（P=.04）.解释：我们已经建立并验证了一个检测胃癌患者淋巴结转移的15基因标记，为潜在改善胃癌患者的治疗结果提供了一个强大的诊断工具。基金：NIH：CA 72851，CA 181572，CA 14792，CA 202797，CA 187956; CPRIT：RP 140784：贝勒萨蒙斯癌症中心polot赠款（AG），VPRT：9610337，城市大学21101115，11102317，11103718; JCYJ 20170307091256048（XW）。(c)2019由Elsevier B出版。V.这是CC BY-NC-ND许可证（http：//creativecommons.org/licenses/by-nc-nd/4.0/）下的开放获取文章。
Background: Although identification of lymph node (LN) metastasis is a well-recognized strategy for improving outcomes in patients with gastric cancer (GC), currently there is lack of availability of adequate molecular biomarkers that can identify such metastasis. Herein we have developed a robust gene-expression signature for detecting LN metastasis in early stage GC by using a transcriptome-wide biomarker discovery and subsequent validation in multiple clinical cohorts.Methods: A total of 532 patients with pathological T1 and T2 GC from 4 different cohorts were analyzed. Two independent datasets (n= 96, and n= 188) were used to establish a gene signature for the identification of LN metastasis in GC patients. The diagnostic performance of our gene-expression signature was subsequently assessed in two independent clinical cohorts using qRT-PCR assays (n= 101, and n= 147), and subsequently compared against conventional tumor markers and image-based diagnostics.Findings: We established a 15-gene signature by analyzing multiple high throughput datasets, which robustly distinguished LN status in both training (AUC= 0.765, 95% CI 0.667-0.863) and validation cohorts (AUC= 0.742, 95% CI 0.630-0.852). Notably, the 15-gene signature was significantly superior compared to the conventional tumor markers, CEA (P=.04) and CA19-9 (P=.005), as well as computed tomography-based imaging (P=.04).Interpretation: Wehave established and validated a 15-gene signature for detecting LN metastasis in GC patients, which offers a robust diagnostic tool for potentially improving treatment outcomes in gastric cancer patients.Fund: NIH: CA72851, CA181572, CA14792, CA202797, CA187956; CPRIT: RP140784: Baylor Sammons Cancer Center polot grants (AG), VPRT: 9610337, CityU 21101115, 11102317, 11103718; JCYJ20170307091256048 (XW). (c) 2019 Published by Elsevier B. V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).