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中国食管鳞状细胞癌队列中差异表达基因的分析

Analysis of Differentially Expressed Genes in a Chinese Cohort of Esophageal Squamous Cell Carcinoma.

作者信息

Liu Gang, Zhao Yuan, Chen Huili, Jia Jinru, Cheng Xiaomin, Wang Fengjie, Ji Qiang, Thorne Rick F, Chen Song, Liu Xiaoying

机构信息

Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450003, China.

Biology Department, School of Life Sciences, Anhui Medical University, Hefei, 230032, China.

出版信息

J Cancer. 2020 Apr 6;11(13):3783-3793. doi: 10.7150/jca.40850. eCollection 2020.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a leading malignancy in China with both high incidence and mortality. Towards improving outcomes, clinically-relevant biomarkers are urgently needed for use as prognostic and treatment targets. Herein we applied RNA-seq for deep sequencing of ten matched pairs of ESCC and adjacent non-cancerous tissues (NT) from Chinese patients. Transcriptomic data mapped to approximately 64% of all annotated genes with 2,047 and 708 unigenes being differentially up-regulated and down-regulated, respectively, between ESCCs and NT samples (<0.05). Dividing cases by pathological grade revealed significant differentially expressed genes (DEG) between ESCC and NT in both low and high differentiation cases (<0.05) whereas gene expression differences were not significantly different between high and low differentiation ESCC tissues (=0.053). Moreover, the majority of ESCC and NT tissues formed clusters in principal component analyses. The veracity of the DEG list was validated in a larger cohort of 45 patient samples, with down-regulated CLIC3, up-regulated CLIC4 and unchanged expression of CLIC2 confirmed in ESCC using quantitative PCR and Western blotting. Our data reveal both previously identified ESCC biomarkers along with novel candidates and represent a ready resource of DEGs in ESCC for further investigation.

摘要

食管鳞状细胞癌(ESCC)是中国一种主要的恶性肿瘤,发病率和死亡率都很高。为了改善治疗效果,迫切需要具有临床相关性的生物标志物作为预后和治疗靶点。在此,我们应用RNA测序对来自中国患者的10对匹配的ESCC和相邻非癌组织(NT)进行深度测序。转录组数据映射到所有注释基因的约64%,ESCC和NT样本之间分别有2047个和708个单基因差异上调和下调(<0.05)。按病理分级对病例进行划分显示,在低分化和高分化病例中,ESCC和NT之间均存在显著差异表达基因(DEG)(<0.05),而高分化和低分化ESCC组织之间的基因表达差异不显著(=0.053)。此外,在主成分分析中,大多数ESCC和NT组织形成了聚类。在一个由45个患者样本组成的更大队列中验证了DEG列表的准确性,使用定量PCR和蛋白质印迹法在ESCC中证实了CLIC3下调、CLIC4上调以及CLIC2表达无变化。我们的数据揭示了先前已确定的ESCC生物标志物以及新的候选标志物,并代表了ESCC中DEG的现成资源以供进一步研究。

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