口腔癌发生过程中基于基因表达的基因组不稳定性替代指标的鉴定

Identification of a Gene-Expression-Based Surrogate of Genomic Instability during Oral Carcinogenesis.

作者信息

Truchard Eléonore, Bertolus Chloé, Martinez Pierre, Thomas Emilie, Saintigny Pierre, Foy Jean-Philippe

机构信息

Sorbonne Université, Department of Maxillo-Facial Surgery, AP-HP, Hôpital Pitié-Salpêtrière, 75013 Paris, France.

Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, 69008 Lyon, France.

出版信息

Cancers (Basel). 2022 Feb 7;14(3):834. doi: 10.3390/cancers14030834.

DOI:10.3390/cancers14030834

PMID:35159101

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8834046/

Abstract

BACKGROUND

Our goal was to identify a gene-expression-based surrogate of genomic instability (GI) associated with the transformation of oral potentially malignant disorder (OPMD) into oral squamous cell carcinoma (OSCC).

METHODS

GI was defined as the fraction of genome altered (FGA). Training sets included the CCLE and TCGA databases. The relevance of the enrichment score of the top correlated genes, referred to as the GIN score, was evaluated in eight independent public datasets from the GEO repository, including a cohort of patients with OPMD with available outcome.

RESULTS

A set of 20 genes correlated with FGA in head and neck SCC were identified. A significant correlation was found between the 20-gene based GIN score and FGA in 95 esophagus SCC (r = 0.59) and 501 lung SCC (r = 0.63), and in 33 OPMD/OSCC (r = 0.38). A significantly increased GIN score was observed at different stages of oral carcinogenesis (normal-dysplasia -OSCC) in five independent datasets. The GIN score was higher in 10 OPMD that transformed into oral cancer compared to 10 nontransforming OPMD ( = 0.0288), and was associated with oral-cancer-free survival in 86 patients with OPMD ( = 0.0081).

CONCLUSIONS

The GIN score is a gene-expression surrogate of GI, and is associated with oral carcinogenesis and OPMD malignant transformation.

摘要

背景

我们的目标是确定一种基于基因表达的基因组不稳定性（GI）替代指标，其与口腔潜在恶性疾病（OPMD）向口腔鳞状细胞癌（OSCC）的转变相关。

方法

GI被定义为基因组改变分数（FGA）。训练集包括CCLE和TCGA数据库。在来自GEO库的八个独立公共数据集中评估了顶级相关基因的富集分数（称为GIN分数）的相关性，其中包括一组有可用结局的OPMD患者。

结果

鉴定出一组与头颈部鳞状细胞癌中FGA相关的20个基因。在95例食管鳞状细胞癌（r = 0.59）、501例肺鳞状细胞癌（r = 0.63）以及33例OPMD/OSCC（r = 0.38）中，发现基于这20个基因的GIN分数与FGA之间存在显著相关性。在五个独立数据集中，在口腔癌发生的不同阶段（正常-发育异常-OSCC）观察到GIN分数显著增加。与10例未转变的OPMD相比，10例转变为口腔癌的OPMD的GIN分数更高（P = 0.0288），并且与86例OPMD患者的无口腔癌生存期相关（P = 0.0081）。