基于TCGA和HADb数据库筛选自噬相关基因 在舌癌中的差异表达及对预后的影响

›› 2020, Vol. 11 ›› Issue (4): 232-236.

基于TCGA和HADb数据库筛选自噬相关基因在舌癌中的差异表达及对预后的影响

张凯¹,张斌²,金晗¹,刘忠爽¹,李莹¹

1. 哈尔滨医科大学附属第二医院硬组织发育与再生研究所
2. 哈尔滨医科大学附属第二医院硬组织发育与再生研究所，黑龙江省医学科学院

收稿日期:2020-07-19 修回日期:2020-11-02 出版日期:2020-12-25 发布日期:2020-12-31
通讯作者: 李莹 E-mail:liying@hrbmu.edu.cn
基金资助:
国家自然科学基金

Differential expression of autophagy related genes in tongue cancer and its influence on prognosis based on TCGA and HADb database

Received:2020-07-19 Revised:2020-11-02 Online:2020-12-25 Published:2020-12-31

摘要/Abstract

摘要： 目的：探讨自噬相关基因（ATG）在舌癌发病机制中的作用，以建立一个基于ATG表达谱的舌癌患者预后预测模型。方法：基于TCGA和HADb数据库，采用Wilcox检验方法确定舌癌中差异表达的ATG，COX回归分析ATG与舌癌患者总生存率的相关性；GO、KEGG分析揭示舌癌中与自噬基因相关的信号通路和生物学过程；评价ATG与舌癌患者临床性状之间的关系。结果：舌癌组织和癌旁组织的ATG具有差异性表达，5个差异基因（VEGFA、ATG9B、WDR45、BAK1、VAMP3）与舌癌患者的总生存率显著相关，可预测患者预后生存；GO、KEGG分析显示多条关键自噬相关通路显著富集，如细胞凋亡、P53信号通路、自噬功能、表皮生长因子受体酪氨酸激酶抑制剂耐药等；ATG9B、VEGFA、WDR45等ATG与患者不同临床病理特征具有显著相关性。结论：VEGFA、ATG9B、WDR45、BAK1、VAMP3等差异自噬基因可预测舌癌的预后。

关键词: 自噬, 舌癌, 预后, 凋亡, 信号通路

Abstract: Objective:? To explore the role of autophagy related genes (ATGs) in the pathogenesis of tongue cancer based on TCGA and HADb database, and to establish a prognosis prediction model of tongue cancer patients based on ATGs expression profile. Methods:?The differential expression of ATGs in tongue cancer was determined by Wilcox test, and the correlation between ATGs and overall survival rate was analyzed by Cox regression. Go and KEGG analysis revealed the signal pathway and biological process related to autophagy gene in tongue cancer. Finally, the relationship between ATGs and clinical characteristics of tongue cancer patients was evaluated. Results:? ATGs in tongue cancer and adjacent tissues were differentially expressed. Five differentially expressed genes (VEGFA, ATG9B, WDR45, BAK1, VAMP3) were significantly related to the overall survival rate of patients with tongue cancer, which could predict the prognosis of survival. Go and KEGG showed significant enrichment of several key autophagy related pathways, such as apoptosis, P53 signaling pathway, autophagy function, EGFR tyrosine kinase inhibitor resistance,etc. Three ATGs (ATG9B, VEGFA, WDR45) were significantly correlated with different clinicopathological features. Conclusions:?We identified five differential autophagy genes, VEGFA, ATG9B, WDR45, BAK1 and VAMP3, which can predict the prognosis of tongue cancer, and have reference value for autophagy research in the field of tongue cancer.

Key words: autophagy, tongue cancer, prognosis, apoptosis, signal pathway

张凯张斌金晗刘忠爽李莹. 基于TCGA和HADb数据库筛选自噬相关基因在舌癌中的差异表达及对预后的影响[J]. 口腔生物医学, 2020, 11(4): 232-236.

参考文献 21

[1]	Fang QG, Shi S, Liu FY, et al.Tongue squamous cell carcinoma as a possible distinct entity in patients under 40 years old[J].Oncol Lett, 2014, 7(6):2099-2102
[2]	Qiu KF, Huang ZX, Huang ZQ, et al.miR-22 regulates cell invasion,migration and proliferation in vitro through inhibiting CD147 expression in tongue squamous cell carcinoma[J].Arch Oral Biol, 2016, 66:92-97
[3]	Tsushima N, Sakashita T, Homma A, et al.The role of prophylactic neck dissection and tumor thickness evaluation for patients with cN0 tongue squamous cell carcinoma[J].Eur Arch Otorhinolaryngol, 2016, 273(11):3987-3992
[4]	Su X, Wang JN, Chen WC, et al.Overexpression of TRIM14 promotes tongue squamous cell carcinoma aggressiveness by activating the NF-κB signaling pathway[J].Oncotarget, 2016, 7(9):9939-9950
[5]	Maejima Y, Kyoi S, Zhai PY, et al.Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2[J].Nat Med, 2013, 19(11):1478-1488
[6]	Wirawan E, Lippens S, Vanden Berghe T, et al.Beclin1: a role in membrane dynamics and beyond[J].Autophagy, 2012, 8(1):6-17
[7]	Gurkar AU, Chu K, Raj L, et al.Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated autophagy during metabolic stress[J].Nat Commun, 2013, 4:2189-
[8]	Levy JMM, Towers CG, Thorburn A.Targeting autophagy in cancer[J].Nat Rev Cancer, 2017, 17(9):528-542
[9]	Li F, Guo H, Yang Y, et al.Autophagy modulation in bladder cancer development and treatment (Review)[J].Oncol Rep, 2019, 42(5):1647-1655
[10]	Ryskalin L, Gaglione A, Limanaqi F, et al.The autophagy status of cancer stem cells in gliobastoma multiforme: From cancer promotion to therapeutic strategies[J].Int J Mol Sci, 2019, 20(15):3824-
[11]	Huang X, Gan GM, Wang XX, et al.The HGF-MET axis coordinates liver cancer metabolism and autophagy for chemotherapeutic resistance[J].Autophagy, 2019, 15(7):1258-1279
[12]	Cosway B, Lovat P.The role of autophagy in squamous cell carcinoma of the head and neck[J].Oral Oncol, 2016, 54:1-6
[13]	Liu PF, Chen H, Cheng J, et al.Association of ATG4B and phosphorylated ATG4B proteins with tumorigenesis and prognosis in oral squamous cell carcinoma[J].Cancers, 2019, 11(12):1854-
[14]	Liao JK, Zhou B, Zhuang XM, et al.Cancer-associated ?broblasts confer cisplatin resistance of tongue cancer via autophagy activation[J].Biomed Pharmacother, 2018, 97:1341-1348
[15]	Su Z, Yang Z, Xu Y, et al.Apoptosis, autophagy, necroptosis, and cancer metastasis[J].Mol Cancer, 2015, 14:48-
[16]	Wellenstein MD, Coffelt SB, Duits DEM, et al.Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis[J].Nature, 2019, 572(7770):538-542
[17]	Guo J, Chen M, Ai G, et al.Hsa_circ_0023404 enhances cervical cancer metastasis and chemoresistance through VEGFA and autophagy signaling by sponging miR-5047[J].Biomed Pharmacother, 2019, 115:108957-
[18]	Neill T, Chen CG, Buraschi S, et al.Catabolic degradation of endothelial VEGFA via autophagy[J].J Biol Chem, 2020, 295(18):6064-6079
[19]	Wang N, Tan HY, Li S, et al.Atg9b deficiency suppresses autophagy and potentiates endoplasmic Reticulum stress-associated hepatocyte apoptosis in hepatocarcinogenesis[J].Theranostics, 2017, 7(8):2325-2338
[20]	Lebovitz CB, Robertson AG, Goya R, et al.Cross-cancer profiling of molecular alterations within the human autophagy interaction network[J].Autophagy, 2015, 11(9):1668-1687
[21]	Chen W, Quan Y, Fan SY, et al.Exosome-transmitted circular RNA hsa_circ_0051443 suppresses hepatocellular carcinoma progression[J].Cancer Lett, 2020, 475:119-128