Lee Doh Young, Kang Young, Im Nu-Ri, Kim Byoungjae, Kwon Tack-Kyun, Jung Kwang-Yoon, Baek Seung-Kuk
Department of Otorhinolaryngology Head and Neck Surgery, Seoul Nation University Boramae Medical Center, Seoul, South Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Chungbuk National University Hospital, Seoul, South Korea.
Laryngoscope. 2021 Apr;131(4):813-819. doi: 10.1002/lary.29025. Epub 2020 Aug 15.
We aimed to analyze gene expression profile of tongue cancer associated with early lymph node metastasis using the cancer genome atlas (TCGA) data.
Basic research.
A total of 515 patients with matched RNAseq data of primary tumor and clinical data from TCGA data were extracted. To compare gene expression profile between early T-stage tongue cancer with cervical lymph node metastasis and late T-stage tongue cancer without cervical metastasis, genomic data of following two groups was assessed; 1) group 1: T1/2 and N2/3 (n = 41), 2) group 2: T4 and N0 (n = 65). Using R and limma package in bioconductor program, differentially expressed genes (DEGs) were extracted. Gene ontology and pathway enrichment analysis were performed using the DAVID online tool. FFPE tissue of 285 patients were evaluated for the validation of relevant genes by imunofluorescence (IF) and immunohistochemical (IHC) stain.
A total of 225 DEGs were found, and 50 genes were highly significant with absolute fold change over eight. Gene ontology and pathway enrichment analysis revealed that most of the upregulated genes were associated with actin cytoskeleton and included following genes: ANKRD23, NO3, PDLIM3, MUSTN1, TNNT3, MYBPC1, MB, MYH3, TTN, ACTA1, and ACTC1. When comparing tongue cancer with cN0pN0 vs. pN0pN+ using the total tongue cancer cohort of TCGA, ACTA1 was the only parameter which was associated with hidden lymph node metastasis in T1/2 (P = .019). Perineural invasion was significantly associated with high expression of ACTA1 (P < .001). IF and IHC analysis revealed that actin was overexpressed, while E-cadherin and N-cadherin were not significantly different.
Actin associated genes, especially overexpression of ACTA1 may be associated with early regional metastasis of tongue cancer.
3 Laryngoscope, 131:813-819, 2021.
我们旨在利用癌症基因组图谱（TCGA）数据分析与早期淋巴结转移相关的舌癌基因表达谱。
基础研究。
从TCGA数据中提取了515例具有原发肿瘤匹配RNA测序数据和临床数据的患者。为比较伴有颈部淋巴结转移的早期T分期舌癌与不伴有颈部转移的晚期T分期舌癌之间的基因表达谱，对以下两组的基因组数据进行了评估；1）第1组：T1/2和N2/3（n = 41），2）第2组：T4和N0（n = 65）。使用生物导体程序中的R和limma软件包提取差异表达基因（DEG）。使用DAVID在线工具进行基因本体和通路富集分析。通过免疫荧光（IF）和免疫组织化学（IHC）染色对285例患者的福尔马林固定石蜡包埋（FFPE）组织进行评估，以验证相关基因。
共发现225个DEG，50个基因具有高度显著性，绝对变化倍数超过8。基因本体和通路富集分析显示，大多数上调基因与肌动蛋白细胞骨架相关，包括以下基因：ANKRD23、NO3、PDLIM3、MUSTN1、TNNT3、MYBPC1、MB、MYH3、TTN、ACTA1和ACTC1。当使用TCGA的全部舌癌队列比较cN0pN0与pN0pN +的舌癌时，ACTA1是唯一与T1/2期隐匿性淋巴结转移相关的参数（P = .019）。神经周围浸润与ACTA1的高表达显著相关（P < .001）。IF和IHC分析显示肌动蛋白过度表达，而E-钙黏蛋白和N-钙黏蛋白无显著差异。
肌动蛋白相关基因，尤其是ACTA1的过表达可能与舌癌的早期区域转移有关。
3《喉镜》，131:813 - 819，2021年。
