A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer.
A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer.
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DOI：
10.1016/j.ebiom.2018.05.025
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发表时间：
2018-06
期刊：
影响因子：
11.1
通讯作者：
Qian Y
中科院分区：
文献类型：
--
作者：
Guo NL;Dowlati A;Raese RA;Dong C;Chen G;Beer DG;Shaffer J;Singh S;Bokhary U;Liu L;Howington J;Hensing T;Qian Y
本研究旨在开发一种多基因检测方法，预测非小细胞肺癌（NSCLC）患者化疗的临床获益，并证实其蛋白表达作为潜在的治疗靶点。在独立的337个速冻NSCLC肿瘤的qRT-PCR测定中分析从微阵列鉴定的160个基因的mRNA表达，以开发预测特征。临床试验JBR.10被纳入验证中。采用风险比法筛选基因，决策树法构建预测模型。在500个FFPE NSCLC样品中用AQUA定量蛋白表达。从具有准确患者分层（P = 0.0043）的训练群组（n = 83）中鉴定出7个基因标签，并且在Kaplan-Meier分析中在独立患者群组（n = 248，P < 0.0001）中验证。在预测获益组中，在训练集（P = 0.035）和验证集（P = 0.0049）中接受辅助化疗的患者的疾病特异性生存率显著更好。在预测的非获益组中，两组接受化疗的患者均无生存获益。用AQUA评分定量的ZNF 71蛋白表达在单独的训练（P = 0.021）和验证（P = 0.047）NSCLC队列中产生了稳健的患者分层。NSCLC组织中CD 27蛋白表达与其mRNA表达呈显著正相关（斯皮尔曼系数= 0.494，P < 0.0088）。多个标签基因在NSCLC进展中具有一致的DNA拷贝数变异、mRNA和蛋白表达。这项研究提出了一种预测性多基因检测和预后蛋白生物标志物，临床上可用于改善NSCLC治疗，对肺癌化疗和免疫治疗具有重要意义。本研究建立了一种基于7-基因检测预测精确肿瘤学化疗的临床益处这项工作使用AQUA技术发现了一种预后蛋白生物标志物ZNF 71作为潜在的伴随测试和治疗靶点这项研究鉴定了具有免疫治疗意义的预后mRNA和蛋白生物标志物CD 27本文的结果将帮助临床医生选择可能受益于化疗的NSCLC患者。化疗所鉴定的预后蛋白标志物也可能成为化疗和免疫治疗的新靶点。
This study aims to develop a multi-gene assay predictive of the clinical benefits of chemotherapy in non-small cell lung cancer (NSCLC) patients, and substantiate their protein expression as potential therapeutic targets. The mRNA expression of 160 genes identified from microarray was analyzed in qRT-PCR assays of independent 337 snap-frozen NSCLC tumors to develop a predictive signature. A clinical trial JBR.10 was included in the validation. Hazard ratio was used to select genes, and decision-trees were used to construct the predictive model. Protein expression was quantified with AQUA in 500 FFPE NSCLC samples. A 7-gene signature was identified from training cohort (n = 83) with accurate patient stratification (P = 0.0043) and was validated in independent patient cohorts (n = 248, P < 0.0001) in Kaplan-Meier analyses. In the predicted benefit group, there was a significantly better disease-specific survival in patients receiving adjuvant chemotherapy in both training (P = 0.035) and validation (P = 0.0049) sets. In the predicted non-benefit group, there was no survival benefit in patients receiving chemotherapy in either set. The protein expression of ZNF71 quantified with AQUA scores produced robust patient stratification in separate training (P = 0.021) and validation (P = 0.047) NSCLC cohorts. The protein expression of CD27 quantified with ELISA had a strong correlation with its mRNA expression in NSCLC tumors (Spearman coefficient = 0.494, P < 0.0088). Multiple signature genes had concordant DNA copy number variation, mRNA and protein expression in NSCLC progression. This study presents a predictive multi-gene assay and prognostic protein biomarkers clinically applicable for improving NSCLC treatment, with important implications in lung cancer chemotherapy and immunotherapy. This paper develops a RT-PCR based 7-gene assay to predict the clinical benefits of chemotherapy for precision oncology This work discovers a prognostic protein biomarker ZNF71 using AQUA technique as a potential companion test and therapeutic target This research identifies prognostic mRNA and protein biomarker CD27 with implications in immunotherapy The results from this paper will help clinicians to select NSCLC patients who might benefit from chemotherapy. The identified prognostic protein biomarkers might also be new therapeutic targets in chemotherapy and immunotherapy.
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影响因子：
2
作者：
Iranmanesh, Seyed;Guo, Nancy
通讯作者：
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影响因子：
3.9
作者：
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168.9
作者：
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影响因子：
20.4
作者：
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通讯作者：
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影响因子：
3.7
作者：
Kim JH;Cheong HS;Park JS;Jang AS;Uh ST;Kim YH;Kim MK;Choi IS;Cho SH;Choi BW;Bae JS;Park CS;Shin HD
通讯作者：
Shin HD