PNAS报道 KRAS相关ERK活性图谱与肺腺癌精准治疗

应用领域:分子生物学,蛋白/抗体/蛋白质组,多组学/蛋白质组/代谢组/脂质组

检测样品:临床肺腺癌样本

检测项目:KRAS阳性,KRAS阴性

参考标准:PNAS,2017,vol. 114,no. 17。

方案摘要

肺腺癌( lung adenocarcinoma )是肺癌的一种,属于非小细胞癌。虽然已经有多种免疫疗法已经EGFR靶向治疗药物在临床上使用,但是疗效欠佳。

 

已知KRAS基因突变是引起肺腺癌重要因素。而KRAS-ERK-脂肪合成信号通路激活与肺腺癌恶性程度密切相关,因而围绕KARS活化及脂肪合成代谢研究,以发现新的诊断和治疗策略获得了众多基础和临床科学家的关注。

 

最近著名杂志PNAS发表了美国斯坦福大学医学院肿瘤学系及德克萨斯大学生化系合作工作:Oncogene KRAS activates fatty acid synthase, resulting inspecific ERK and lipid signatures associated with lung adenocarcinoma. 4300–4305,PNAS,2017,vol. 114,no. 17。

 

文章最主要工作之一,作者使用ProteinSimple Nanopro1000纳米级免疫检测(nanoimmunoassay (NIA)),系统,建立KARS相关ERK(extracellular regulated protein kinases)活化图谱。作者发现,KARS阳性肿瘤特异性出现ERK2磷酸化图谱增强,KRAS阴性肿瘤则特异性出现ERK1磷酸化图谱增强。

1515392202929713.png

1515392213962903.png

NIA ERK protein signatures: (A) normal vs. humanKRAS-associated lung cancer tissue (n = 6), (B) normal vs. human non-KRAS lung cancer tissue (n = 6), and percentages oftotal ERK in (C) KRAS tumors and (D) non-KRAS tumors.*Statistical significance by t test for P value <0.05. **Statistical significance by t test for P value <0.01.

 

作者特别强调了使用Nanopro1000纳米级免疫分析系统在癌症精准诊断治疗中的意义:

极高灵敏度,可以在微量临床样本中检测蛋白磷酸化图谱变化

独特的蛋白质磷酸化图谱检测,有助于基于此开发相关药物及选择临床治疗方案

We identified unique proteomic and lipid signatures of KRAS lung adenocarcinoma.By NIA, ERK1 vs. ERK2 protein activation allowed us to distinguish betweenKRAS-positive and -negative tumors in clinical specimens. NIA is a highly sensitive nanofluidic approach that is highly tractable for the examination ofeven picograms of protein derived from as few as 20 cells to measure proteins andtheir phosphorylation state (40, 41). Thus, NIA measurement of ERK may beuseful in the diagnosis of lung adenocarcinoma.

 

作者接下来的工作将是在临床研究中,选择靶向KRAS-ERK-脂肪合成途径的药物,治疗对于免疫治疗及EGFR靶向治疗不敏感的病人。

Ourresults suggest that KRAS-induced lung adenocarcinoma may be particularlysusceptible to the targeted therapeutic inhibition of FASN (acid synthase(FASN).) . More clinical workis needed to verify this hypothesis.

或致电ProteinSimple中国:4000-863-973

1515392241805455.jpg

相关产品
店铺 下载
咨询留言 一键拨号