Identification of Hub Genes and Key Pathways Associated with Peripheral T-cell Lymphoma

Hai-xia Gao , Meng-bo Wang , Si-jing Li , Jing Niu , Jing Xue , Jun Li , Xin-xia Li

Current Medical Science ›› 2020, Vol. 40 ›› Issue (5) : 885 -899.

PDF
Current Medical Science ›› 2020, Vol. 40 ›› Issue (5) : 885 -899. DOI: 10.1007/s11596-020-2250-9
Article

Identification of Hub Genes and Key Pathways Associated with Peripheral T-cell Lymphoma

Author information +
History +
PDF

Abstract

Peripheral T-cell lymphoma (PTCL) is a very aggressive and heterogeneous hematological malignancy and has no effective targeted therapy. The molecular pathogenesis of PTCL remains unknown. In this study, we chose the gene expression profile of GSE6338 from the Gene Expression Omnibus (GEO) database to identify hub genes and key pathways and explore possible molecular pathogenesis of PTCL by bioinformatic analysis. Differentially expressed genes (DEGs) between PTCL and normal T cells were selected using GEO2R tool. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, the Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) were utilized to construct protein-protein interaction (PPI) network and perform module analysis of these DEGs. A total of 518 DEGs were identified, including 413 down-regulated and 105 up-regulated genes. The down-regulated genes were enriched in osteoclast differentiation, Chagas disease and mitogen-activated protein kinase (MAPK) signaling pathway. The up-regulated genes were mainly associated with extracellular matrix (ECM)-receptor interaction, focal adhesion and pertussis. Four important modules were detected from the PPI network by using MCODE software. Fifteen hub genes with a high degree of connectivity were selected. Our study identified DEGs, hub genes and pathways associated with PTCL by bioinformatic analysis. Results provide a basis for further study on the pathogenesis of PTCL.

Keywords

peripheral T-cell lymphomas / bioinformatic analysis / protein-protein interaction / hub genes / pathways

Cite this article

Download citation ▾
Hai-xia Gao, Meng-bo Wang, Si-jing Li, Jing Niu, Jing Xue, Jun Li, Xin-xia Li. Identification of Hub Genes and Key Pathways Associated with Peripheral T-cell Lymphoma. Current Medical Science, 2020, 40(5): 885-899 DOI:10.1007/s11596-020-2250-9

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

LevalLD, BisigB, ThielenC, et al.. Molecular classification of T-cell lymphomas. Crit Rev Oncol Hematol, 2009, 72(2): 125-143

[2]

FossFM, ZinzaniPL, VoseJM, et al.. Peripheral T-cell lymphoma. Blood, 2011, 117(25): 6756-6767

[3]

ArmitageJ O. The aggressive peripheral T-cell lymphomas: 2012 update on diagnosis, risk stratification, and management. Am. J. Hematol, 2012, 87: 511-519

[4]

ScarisbrickJJ, KimYH, WhittakerSJ, et al.. Prognostic factors, prognostic indices and staging in mycosis fungoides and Sézary syndrome: where are we now?. Br J Dermatol, 2014, 170(6): 1226-1236

[5]

Martin-SanchezE, OdqvistL, Rodriguez-PinillaSM, et al.. PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases. Plos One, 2014, 9(9): e112148

[6]

PearsonJ D, Lee JasonKH, Bacani JulinorTC, et al.. NPM-ALK: The Prototypic Member of a Family of Oncogenic Fusion Tyrosine Kinases. J Signal Transduct, 2012, 2012(4): 123253

[7]

BarrecaA, LasorsaE, RieraL, et al.. Anaplastic lymphoma kinase in human cancer. J Mol Endocrinol, 2011, 47(1): 11-23

[8]

O’LearyH, SavageKJ. The spectrum of peripheral T-cell lymphomas. Curr Opin Hematol, 2009, 16(4): 292

[9]

Gambacorti-PasseriniC, MessaC, PoglianiEM. Crizotinib in anaplastic large-cell lymphoma. N Engl J Med, 2011, 364(8): 775-776

[10]

IntlekoferAM, YounesA. From empiric to mechanism-based therapy for peripheral T cell lymphoma. Int J Hematol, 2014, 99(3): 249-262

[11]

HorwitzSM, AdvaniRH, BartlettNL, et al.. Objective responses in relapsed T-cell lymphomas with singleagent brentuximab vedotin. Blood, 2014, 123(20): 3095-3100

[12]

DunleavyK, PiekarzRL, ZainJ, et al.. New Strategies in Peripheral T-cell lymphoma: Understanding Tumor Biology and Developing Novel Therapies. Clin Cancer Res, 2010, 16(23): 5608

[13]

MoskowitzAJ, LunningMA, HorwitzSM. How I treat the peripheral T-cell lymphomas. Blood, 2014, 123(17): 2636-2644

[14]

PiccalugaPP, AgostinelliC, CalifanoA, et al.. Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets. J Clin Invest, 2007, 117(3): 823-834

[15]

DavisS, MeltzerPS. GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor. Bioinformatics, 2007, 23(14): 1846-1847

[16]

AshburnerM, BallCA, BlakeJA, et al.. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet, 2000, 25(1): 25-29

[17]

KanehisaM, GotoS. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res, 2000, 27(1): 29-34

[18]

HuangDW, ShermanBT, LempickiRA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc, 2009, 4(1): 44-57

[19]

SzklarczykD, FranceschiniA, WyderS, et al.. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res, 2015, 43: D447

[20]

Ono K, Muetze T, Kolishovski G, et al. CyREST: Turbocharging Cytoscape Access for External Tools via a RESTful API. F1000Res, 2015,4

[21]

BaderGD, HogueCW. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics, 2003, 4(1): 2

[22]

SwerdlowSH, CampoE, PileriSA, et al.. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood, 2016, 127(20): 2375-2390

[23]

WangC, MckeithanTW, GongQ, et al.. IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma. Blood, 2015, 126(15): 1741-1752

[24]

PiccalugaPP, TabanelliV, PileriSA. Molecular genetics of peripheral T-cell lymphomas. Int J Hematol, 2014, 99(3): 219-226

[25]

PaluchEK, AspalterIM, SixtM. Focal Adhesion-Independent Cell Migration. Annu Rev Cell Dev Biol, 2016, 32(1): 469

[26]

ZhuJJ, LuoJ, WangW, et al.. Inhibition of FASN reduces the synthesis of medium-chain fatty acids in goat mammary gland. Animal, 2014, 8(9): 1469-1478

[27]

WangY, ZhangM, XuH, et al.. Discovery and validation of the tumor-suppressive function of long noncoding RNA PANDA in human diffuse large B-cell lymphoma through the inactivation of MAPK/ERK signaling pathway. Oncotarget, 2017, 8(42): 72182-72196

[28]

MorachisJM, MurawskyCM, EmersonBM. Regulation of the p53 transcriptional response by structurally diverse core promoters. Genes Dev, 2010, 24(2): 135-147

[29]

IslamS, QiW, MoralesC, et al.. Disruption of Aneuploidy and Senescence Induced by Aurora Inhibition Promotes Intrinsic Apoptosis in Double Hit or Double Expressor Diffuse Large B-cell Lymphomas. Mol Cancer Ther, 2017, 16(10): 2083-2093

[30]

LaJR, SchafernakKT, GeyerJT, et al.. Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations. Blood, 2016, 128(8): 1093-1100

[31]

LiY, ShiX, YangW, et al.. Transcriptome profiling of lncRNA and co-expression networks in esophageal squamous cell carcinoma by RNA sequencing. Tumour Biol, 2016, 37(10): 1-10

[32]

LiS, LiH, XuY, et al.. Identification of candidate biomarkers for epithelial ovarian cancer metastasis using microarray data. Oncol Lett, 2017, 14(4): 3967-3974

[33]

NingX, DengY. Identification of key pathways and genes influencing prognosis in bladder urothelial carcinoma. Onco Targets Ther, 2017, 10: 1673-1686

[34]

OttGR, ChengM, LearnKS, et al.. Discovery of Clinical Candidate CEP-37440, a Selective Inhibitor of Focal Adhesion Kinase (FAK) and Anaplastic Lymphoma Kinase (ALK). J Med Chem, 2016, 59(16): 7478-7496

[35]

BoschR, Dieguez-GonzalezR, MorenoMJ, et al.. Focal adhesion protein expression in human diffuse large B-cell lymphoma. Histopathology, 2014, 65(1): 119-131

[36]

UddinS, HussainAR, SirajAK, et al.. Role of phosphatidylinositol 3,-kinase/AKT pathway in diffuse large B-cell lymphoma survival. Blood, 2006, 108(13): 4178-4186

[37]

HasselblomS, HanssonU, OlssonM, et al.. High immunohistochemical expression of p-AKT predicts inferior survival in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Br J Haematol, 2010, 149(4): 560-568

[38]

HongJY, HongME, ChoiMK, et al.. The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: a clinicopathological study of 262 cases. Ann Oncol, 2014, 25(1): 182-188

[39]

BaiR, OuyangTC, MorrisS, et al.. Nucleophosminanaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway. Blood, 2000, 96(13): 4319

[40]

ChowC, LiuAY, ChanWS, et al.. AKT plays a role in the survival of the tumor cells of extranodal NK/T-cell lymphoma, nasal type. Haematologica, 2005, 90(2): 274

[41]

HuangY, DeRA, DeLL, et al.. Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type. Blood, 2010, 115(6): 1226

[42]

RassidakisGZ, FeretzakiM, AtwellC, et al.. Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma. Blood, 2005, 105(2): 827-829

[43]

SlupianekA, Nieborowska-SkorskaM, HoserG, et al.. Role of phosphatidylinositol 3-kinase-Akt pathway in nucleophosmin/anaplastic lymphoma kinase-mediated lymphomagenesis. Cancer Res, 2001, 61(5): 2194-2199

[44]

YamanakaY, TagawaH, TakahashiN, et al.. Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia. Blood, 2009, 114(15): 3265-3275

[45]

HongJY, HongME, ChoiMK, et al.. The Clinical Significance of Activated p-AKT Expression in Peripheral T-cell Lymphoma. Anticancer Res, 2015, 35(4): 2465-2474

[46]

HuangW, AugustA. The signaling symphony: T cell receptor tunes cytokine-mediated T cell differentiation. J Leukoc Biol, 2015, 97(3): 477-485

[47]

MartinezDB, CuadrosME, RuizdlPA, et al.. Differential expression of NF-kappaB pathway genes among peripheral T-cell lymphomas. Leukemia, 2005, 19(12): 2254

[48]

XiangL, XieG, OuJ, et al.. The Extra Domain A of Fibronectin Increases VEGF-C Expression in Colorectal Carcinoma Involving the PI3K/AKT Signaling Pathway. Plos One, 2012, 7(4): e35378

[49]

LossosIS, CzerwinskiDK, AlizadehAA, et al.. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med, 2004, 350: 1828-1837

[50]

MalumbresR, ChenJ, TibshiraniR, et al.. Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP. Blood, 2008, 111(12): 5509

[51]

VanesaG, MiguelGJ, JavierS, et al.. Extracellular Tumor-Related mRNA in Plasma of Lymphoma Patients and Survival Implications. Plos One, 2009, 4(12): e8173

[52]

Zamani-AhmadmahmudiM, AghasharifS, IlbeigiK. Prognostic efficacy of the human B-cell lymphoma prognostic genes in predicting disease-free survival (DFS) in the canine counterpart. BMC Vet Res, 2017, 13(1): 17

[53]

ZeisbergM, NeilsonEG. Biomarkers for epithelialmesenchymal transitions. J Clin Invest, 2009, 119(6): 1429-1437

[54]

BrandtS, MontagnaC, GeorgisA, et al.. The combined expression of the stromal markers fibronectin and SPARC improves the prediction of survival in diffuse large B-cell lymphoma. Exp Hematol Oncol, 2013, 2(1): 27

[55]

ZhangH, TengX, LiuZ, et al.. Gene expression profile analyze the molecular mechanism of CXCR7 regulating papillary thyroid carcinoma growth and metastasis. J Exp Clin Cancer Res, 2015, 34(1): 16

[56]

ZenzR, WagnerEF. Jun signalling in the epidermis: From developmental defects to psoriasis and skin tumors. Int J Biochem Cell Biol, 2006, 38(7): 1043-1049

[57]

ZhangJ, WuZ, SavinA, et al.. The c-Jun and JunB transcription factors facilitate the transit of classical Hodgkin lymphoma tumour cells through G1. Sci Rep, 2018, 8(1): 16019

[58]

RucoLP, PomponiD, PigottR, et al.. Cytokine production (IL-1 alpha, IL-1 beta, and TNF alpha) and endothelial cell activation (ELAM-1 and HLA-DR) in reactive lymphadenitis, Hodgkin’s disease, and in non-Hodgkin’s lymphomas. An immunocytochemical study. Am J Pathol, 1990, 137(5): 1163-1171

[59]

GotoN, TsurumiH, TakemuraM, et al.. Serum Soluble Tumor Necrosis Factor Receptor 1 Level is Associated with the Outcome of Diffuse Large B-Cell Lymphoma Patients Treated with the CHOP or R-CHOP Regimen. J Clin Exp Hematop, 2014, 91(4): 117-127

[60]

NakamuraN, GotoN, TsurumiH, et al.. Serum level of soluble tumor necrosis factor receptor 2 is associated with the outcome of patients with diffuse large B-cell lymphoma treated with the R-CHOP regimen. Eur J Haematol, 2013, 91(4): 322-331

[61]

HonmaY, SugitaN, KobayashiT, et al.. TNF-α expression in tumor cells as a novel prognostic marker for diffuse large B-cell lymphoma, not otherwise specified. Am J Surg Pathol, 2014, 38(2): 228-234

[62]

DlouhyI, FilellaX, RoviraJ, et al.. High serum levels of soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) are associated with adverse clinical features and predict poor outcome in diffuse large B-cell lymphoma. Leuk Res, 2017, 59: 20

[63]

KatoH, NagasakaT, IchikawaA, et al.. Tumor necrosis factor-beta gene expression and its relationship to the clinical features and histopathogenesis of peripheral T-cell lymphomas. Leuk Lymphoma, 1994, 16(1–2): 125-133

[64]

NocturneG, BoudaoudS, LyB, et al.. Impact of anti-TNF therapy on NK cells function and on immunosurveillance against B-cell lymphomas. J Autoimmun, 2017, 80: 56-64

[65]

RamezaniS, ShirdelA, RafatpanahH, et al.. Assessment of HTLV-1 proviral load, LAT, BIM, c-FOS and RAD51 gene expression in adult T cell leukemia/lymphoma. Med Microbiol Immunol, 2017, 206(4): 327-335

[66]

BoiM, TodaroM, VurchioV, et al.. Therapeutic efficacy of the bromodomain inhibitor OTX015/MK-8628 in ALK-positive anaplastic large cell lymphoma: an alternative modality to overcome resistant phenotypes. Oncotarget, 2016, 7(48): 79637-79653

[67]

GuoX, KoffJL, MoffittAB, et al.. Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype. Oncogene, 2017, 36(29): 4224-4232

[68]

SebestyénA, HajduM, KisL, et al.. Smad4-independent, PP2A-dependent apoptotic effect of exogenous transforming growth factor beta 1 in lymphoma cells. Exp Cell Res, 2007, 313(15): 3167-3174

[69]

MacdonaldI, WangH, GrandR, et al.. Transforming growth factor-beta 1 cooperates with anti-immunoglobulin for the induction of apoptosis in group I (biopsy-like) Burkitt lymphoma cell lines. Blood, 1996, 87(3): 1147

AI Summary AI Mindmap
PDF

103

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/