A 10-gene classifier for distinguishing headand neck squamous cell carcinoma and lung squamous cell carcinoma

A 10-gene classifier for distinguishing headand neck squamous cell carcinoma and lung squamous cell carcinoma
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DOI:
10.1158/1078-0432.ccr-06-1670
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发表时间:
2007-05-15
影响因子:
11.5
通讯作者:
Showe, Louise C.
Showe, Louise C.
中科院分区:
医学1区
文献类型:
--
作者:
Vachani, Anil;Nebozhyn, Michael;Showe, Louise C.

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目的:头颈鳞状细胞癌(HNSCC)患者发生转移性鳞状细胞癌的风险非常高。由于这些患者通常大量吸烟,因此他们也有患第二原发癌症的风险,其中最常见的是肺鳞状细胞癌(LSCC)。肺转移瘤和原发性 LSCC 之间的区别目前基于某些临床和组织学标准,尽管这种方法的准确性仍然存在疑问。 实验设计:使用惩罚判别分析对来自单个中心的 28 名 HNSCC 或 LSCC 患者的基因表达模式进行了分析。对来自四个独立 Affymetrix 数据集的 134 名受试者的先前发布的数据进行了验证。结果:我们鉴定了一组 10 个基因(CXCL13 COL6A2、SFTPB、KRT14、TSPYL5、TMP3、KLK10、MMP1 GAS1 和 MYH2),可以准确地区分这两种肿瘤类型。这个 10 基因分类器在来自四个独立数据集的 122 名受试者上进行了验证,平均准确度为 96%。基因表达值通过 12 个独立样本(7 个 HNSCC 和 5 个 LSCC)的定量逆转录 PCR 进行验证。 10 基因分类器还用于确定既往患有 HNSCC 的患者的 12 个肺部病变的起源部位。结论:结果表明,使用这 10 个基因进行惩罚判别分析在确定既往患有头颈恶性肿瘤的患者肺部鳞状细胞癌的起源方面将非常准确。
Purpose: The risk of developing metastatic squamous cell carcinoma for patients with head and neck squamous cell carcinoma (HNSCC) is very high. Because these patients are often heavy tobacco users, they are also at risk for developing a second primary cancer, with squamous cell carcinoma of the lung (LSCC) being the most common. The distinction between a lung metastasis and a primary LSCC is currently based on certain clinical and histologic criteria, although the accuracy of this approach remains in question.Experimental Design: Gene expression patterns derived from 28 patients with HNSCC or LSCC from a single center were analyzed using penalized discriminant analysis. Validation was done on previously published data for 134 total subjects from four independent Affymetrix data sets.Results: We identified a panel of 10 genes (CXCL13 COL6A2, SFTPB, KRT14, TSPYL5, TMP3, KLK10, MMP1 GAS1, and MYH2) that accurately distinguished these two tumor types. This 10-gene classifier was validated on 122 subjects derived from four independent data sets and an average accuracy of 96% was shown. Gene expression values were validated by quantitative reverse transcription-PCR derived on 12 independent samples (seven HNSCC and five LSCC). The 10-gene classifier was also used to determine the site of origin of 12 lung lesions from patients with prior HNSCC.Conclusions: The results suggest that penalized discriminant analysis using these 10 genes will be highly accurate in determining the origin of squamous cell carcinomas in the lungs of patients with previous head and neck malignancies.