Novel biomarkers that assist in accurate discrimination of squamous cell carcinoma from adenocarcinoma of the lung.

Novel biomarkers that assist in accurate discrimination of squamous cell carcinoma from adenocarcinoma of the lung.
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DOI:
10.1186/s12885-016-2792-1
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发表时间:
2016-09-29
期刊:
影响因子:
3.8
通讯作者:
Kawaji H
Kawaji H
中科院分区:
医学2区
文献类型:
--
作者:
Takamochi K;Ohmiya H;Itoh M;Mogushi K;Saito T;Hara K;Mitani K;Kogo Y;Yamanaka Y;Kawai J;Hayashizaki Y;Oh S;Suzuki K;Kawaji H

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基于癌症类型的分子和组织学特征的靶向治疗正在成为标准实践。肺癌的最有效方案在鳞状细胞癌(SCC)和腺癌(AD)之间是不同的。因此,精确的诊断是至关重要的,但这一直是困难的,特别是对于低分化SCC(PDSCC)和没有鳞屑生长成分的AD(非鳞屑AD)。因此,迫切需要能够进行精确诊断的生物标志物。基因表达帽分析(CAGE)是一种用于通过用下一代测序确定加帽RNA分子的5'端来量化整个基因组的启动子活性的方法。我们对97例手术切除的肺癌冷冻组织(22例SCC和75例AD)进行了CAGE,并在一个独立的组(29例SCC和45例AD)中通过免疫组化分析(IHC)证实了这一发现。使用全基因组启动子活性谱,我们证实了SCC(CK 5,CK 6,p40和桥粒芯糖蛋白-3)和AD(TTF-1和napsin A)的IHC中使用的已知分子标记的表达在SCC和AD之间是不同的。我们鉴定了两种新的候选标记物,SCC的SPATS 2和AD的ST 6 GALNAC 1,在区分PDSCC和非麻风AD中显示出与已知标记物相当的性能和互补效用。我们随后在一个独立的组中通过IHC证实了它们在蛋白质水平上的效用。我们鉴定了两个基因SPATS 2和ST 6 GALNAC 1作为区分SCC和AD的新的互补生物标志物。这些发现将有助于更准确地诊断NSCLC,这对于肺癌的精准医学至关重要。本文的在线版本(doi:10.1186/s12885-016-2792-1)包含补充材料,可供授权用户使用。
Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed. Cap Analysis of Gene Expression (CAGE) is a method used to quantify promoter activities across the whole genome by determining the 5’ ends of capped RNA molecules with next-generation sequencing. We performed CAGE on 97 frozen tissues from surgically resected lung cancers (22 SCC and 75 AD), and confirmed the findings by immunohistochemical analysis (IHC) in an independent group (29 SCC and 45 AD). Using the genome-wide promoter activity profiles, we confirmed that the expression of known molecular markers used in IHC for SCC (CK5, CK6, p40 and desmoglein-3) and AD (TTF-1 and napsin A) were different between SCC and AD. We identified two novel marker candidates, SPATS2 for SCC and ST6GALNAC1 for AD, as showing comparable performance and complementary utility to the known markers in discriminating PDSCC and non-lepidic AD. We subsequently confirmed their utility at the protein level by IHC in an independent group. We identified two genes, SPATS2 and ST6GALNAC1, as novel complemental biomarkers discriminating SCC and AD. These findings will contribute to a more accurate diagnosis of NSCLC, which is crucial for precision medicine for lung cancer. The online version of this article (doi:10.1186/s12885-016-2792-1) contains supplementary material, which is available to authorized users.
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