TMEM158 May Serve as a Diagnostic Biomarker for Anaplastic Thyroid Carcinoma: An Integrated Bioinformatic Analysis

Han-ning Li , Ya-ying Du , Tao Xu , Rui Zhang , Ge Wang , Zheng-tao Lv , Xing-rui Li

Current Medical Science ›› 2021, Vol. 40 ›› Issue (6) : 1137 -1147.

PDF
Current Medical Science ›› 2021, Vol. 40 ›› Issue (6) : 1137 -1147. DOI: 10.1007/s11596-020-2296-8
Article

TMEM158 May Serve as a Diagnostic Biomarker for Anaplastic Thyroid Carcinoma: An Integrated Bioinformatic Analysis

Author information +
History +
PDF

Abstract

Anaplastic thyroid carcinoma (ATC) is a rare but extremely lethal malignancy. However, little is known about the pathogenesis of ATC. Given its high mortality, it is critical to improve our understanding of ATC pathogenesis and to find new diagnostic biomarkers. In the present study, two gene microarray profiles (GSE53072 and GSE65144), which included 17 ATC and 17 adjacent non-tumorous tissues, were obtained. Bioinformatic analyses were then performed. Immunohistochemistry (IHC) and receiver operating characteristic (ROC) curves were then used to detect transmembrane protein 158 (TMEM158) expression and to assess diagnostic sensitivity. A total of 372 differentially expressed genes (DEGs) were identified. Through protein-protein interaction (PPI) analysis, we identified a significant module with 37 upregulated genes. Most of the genes in this module were related to cell-cycle processes. After co-expression analysis, 132 hub genes were selected for further study. Nine genes were identified as both DEGs and genes of interest in the weighted gene co-expression network analysis (WGCNA). IHC and ROC curves confirmed that TMEM158 was overexpressed in ATC tissue as compared with other types of thyroid cancer and normal tissue samples. We identified 8 KEGG pathways that were associated with high expression of TMEM158, including aminoacyl-tRNA biosynthesis and DNA replication. Our results suggest that TMEM158 may be a potential oncogene and serve as a diagnostic indicator for ATC.

Keywords

anaplastic thyroid carcinoma / transmembrane protein 158 / bioinformatics / weighted gene co-expression network analysis / gene set enrichment analysis

Cite this article

Download citation ▾
Han-ning Li, Ya-ying Du, Tao Xu, Rui Zhang, Ge Wang, Zheng-tao Lv, Xing-rui Li. TMEM158 May Serve as a Diagnostic Biomarker for Anaplastic Thyroid Carcinoma: An Integrated Bioinformatic Analysis. Current Medical Science, 2021, 40(6): 1137-1147 DOI:10.1007/s11596-020-2296-8

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

BrayF, FerlayJ, SoerjomataramI, et al.. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424

[2]

LimH, DevesaSS, SosaJA, et al.. Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974–2013. JAMA, 2017, 317(13): 1338-1348

[3]

SegerhammarI, LarssonC, NilssonIL, et al.. Anaplastic carcinoma of the thyroid gland: treatment and outcome over 13 years at one institution. J Surg Oncol, 2012, 106(8): 981-986

[4]

SmallridgeRC, AinKB, AsaSL, et al.. American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid, 2012, 22(11): 1104-1139

[5]

MohebatiA, DilorenzoM, PalmerF, et al.. Anaplastic thyroid carcinoma: a 25-year single-institution experience. Ann Surg Oncol, 2014, 21(5): 1665-1670

[6]

RagazziM, CiarrocchiA, SancisiV, et al.. Update on anaplastic thyroid carcinoma: morphological, molecular, and genetic features of the most aggressive thyroid cancer. Int J Endocrinol, 2014, 2014: 790834

[7]

TangX, XuY, LuL, et al.. Identification of key candidate genes and small molecule drugs in cervical cancer by bioinformatics strategy. Cancer Manag Res, 2018, 10: 3533-3549

[8]

CuiX, YiQ, JingX, et al.. Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis. Cell Physiol Biochem, 2018, 50(1): 41-51

[9]

HuS, LiaoY, ChenL. Identification of Key Pathways and Genes in Anaplastic Thyroid Carcinoma via Integrated Bioinformatics Analysis. Med Sci Monit, 2018, 24: 6438-6448

[10]

HuangY, TaoY, LiX, et al.. Bioinformatics analysis of key genes and latent pathway interactions based on the anaplastic thyroid carcinoma gene expression profile. Oncol Lett, 2017, 13(1): 167-176

[11]

LangfelderP, HorvathS. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics, 2008, 9: 559

[12]

BarrettT, WilhiteSE, LedouxP, et al.. NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res, 2013, 41: D991-995(Database issue)

[13]

PitaJM, FigueiredoIF, MouraM M, et al.. Cell cycle deregulation and TP53 and RAS mutations are major events in poorly differentiated and undifferentiated thyroid carcinomas. J Clin Endocrinol Metab, 2014, 99(3): E497-507

[14]

Von RoemelingCA, MarlowLA, PinkertonAB, et al.. Aberrant lipid metabolism in anaplastic thyroid carcinoma reveals stearoyl CoA desaturase 1 as a novel therapeutic target. J Clin Endocrinol Metab, 2015, 100(5): E697-709

[15]

IrizarryRA, HobbsB, CollinF, et al.. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics, 2003, 4(2): 249-264

[16]

LeekJT, JohnsonWE, ParkerHS, et al.. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics, 2012, 28(6): 882-883

[17]

RitchieME, PhipsonB, WuD, et al.. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res, 2015, 43(7): e47

[18]

GiordanoTJ, AuAY, KuickR, et al.. Delineation, functional validation, and bioinformatic evaluation of gene expression in thyroid follicular carcinomas with the PAX8-PPARG translocation. Clin Cancer Res, 2006, 12: 1983-1993Pt 1

[19]

KanehisaM, GotoS. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res, 2000, 28(1): 27-30

[20]

YuG, WangLG, HanY, et al.. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics, 2012, 16(5): 284-287

[21]

SzklarczykD, MorrisJH, CookH, et al.. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res, 2017, 45(D1): D362-d368

[22]

ShannonP, MarkielA, OzierO, et al.. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res, 2003, 13(11): 2498-2504

[23]

SaitoR, SmootME, OnoK, et al.. A travel guide to Cytoscape plugins. Nat Methods, 2012, 9(11): 1069-1076

[24]

BotiaJA, VandrovcovaJ, ForaboscoP, et al.. An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks. BMC Syst Biol, 2017, 11(1): 47

[25]

YipAM, HorvathS. Gene network interconnectedness and the generalized topological overlap measure. BMC Bioinformatics, 2007, 8: 22

[26]

RavaszE, SomeraAL, MongruDA, et al.. Hierarchical organization of modularity in metabolic networks. Science, 2002, 297(5586): 1551-1555

[27]

PathanM, KeerthikumarS, AngCS, et al.. FunRich: An open access standalone functional enrichment and interaction network analysis tool. Proteomics, 2015, 15(15): 2597-2601

[28]

MoothaVK, LindgrenCM, ErikssonKF, et al.. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet, 2003, 34(3): 267-273

[29]

SubramanianA, TamayoP, MoothaVK, et al.. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A, 2005, 102(43): 15545-15550

[30]

HishinumaA, TakamatsuJ, KannoY, et al.. Analysis of the promoter of the thyrotropin receptor gene and the entire genomic sequence of thyroid transcription factor-1 in familial congenital hypothyroidism due to thyrotropin unresponsiveness. Thyroid, 1998, 8(4): 305-309

[31]

OrdóñezNG, El-NaggarAK, HickeyRC, et al.. Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases. Am J Clin Pathol, 1991, 96(1): 15-24

[32]

Albores-SaavedraJ, HernandezM, Sanchez-SosaS, et al.. Histologic variants of papillary and follicular carcinomas associated with anaplastic spindle and giant cell carcinomas of the thyroid: an analysis of rhabdoid and thyroglobulin inclusions. Am J Surg Pathol, 2007, 31(5): 729-736

[33]

OguchiH, KimuraS. Multiple transcripts encoded by the thyroid-specific enhancer-binding protein (T/EBP)/thyroid-specific transcription factor-1 (TTF-1) gene: evidence of autoregulation. Endocrinology, 1998, 139(4): 1999-2006

[34]

Ryff-De LecheA, StaubJJ, Kohler-FadenR, et al.. Thyroglobulin production by malignant thyroid tumors. An immunocytochemical and radioimmunoassay study. Cancer, 1986, 57(6): 1145-1153

[35]

MiettinenM, FranssilaKO. Variable expression of keratins and nearly uniform lack of thyroid transcription factor 1 in thyroid anaplastic carcinoma. Hum Pathol, 2000, 31(9): 1139-1145

[36]

ZollingerAJ, SmithML. Fibronectin, the extracellular glue. Matrix Biol, 2017, 60–61: 27-37

[37]

IozzoRV, SchaeferL. Proteoglycan form and function: A comprehensive nomenclature of proteoglycans. Matrix Biol, 2015, 42: 11-55

[38]

WalkerC, MojaresE, Del Río HernándezA. Role of Extracellular Matrix in Development and Cancer Progression. Int J Mol Sci, 2018, 19(10): 3028

[39]

SullivanWJ, MullenPJ, SchmidEW, et al.. Extracellular Matrix Remodeling Regulates Glucose Metabolism through TXNIP Destabilization. Cell, 2018, 175(1): 117-132.e121

[40]

SunHF, YangXL, ZhaoY, et al.. Loss of TMEM126A promotes extracellular matrix remodeling, epithelial-to-mesenchymal transition, and breast cancer metastasis by regulating mitochondrial retrograde signaling. Cancer Lett, 2019, 440–441: 189-201

[41]

BerteroT, OldhamWM, GrassetEM, et al.. Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy. Cell Metab, 2019, 29(1): 124-140.e110

[42]

ZhangJ, WangP, DykstraM, et al.. Platelet-derived growth factor receptor-alpha promotes lymphatic metastases in papillary thyroid cancer. J Pathol, 2012, 228(2): 241-250

[43]

HomsiJ, DaudAI. Spectrum of activity and mechanism of action of VEGF/PDGF inhibitors. Cancer Control, 2007, 14(3): 285-294

[44]

ProvencioM, García-CampeloR, ISLAD, et al.. Clinical-molecular factors predicting response and survival for tyrosine-kinase inhibitors. Clin Transl Oncol, 2009, 11(7): 428-436

[45]

FrohlichE, WahlR. Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases. Front Immunol, 2017, 8: 521

[46]

HaberkornU, AltmannA, JiangS, et al.. Iodide uptake in human anaplastic thyroid carcinoma cells after transfer of the human thyroid peroxidase gene. Eur J Nucl Med, 2001, 28(5): 633-638

[47]

GugliettaS, RescignoM. Hypercoagulation and complement: Connected players in tumor development and metastases. Semin Immunol, 2016, 28(6): 578-586

[48]

MasagoK, FujitaS, MioT, et al.. Clinical significance of the ratio between the alpha 2 plasmin inhibitor-plasmin complex and the thrombin-antithrombin complex in advanced non-small cell lung cancer. Med Oncol, 2011, 28(1): 351-356

[49]

HanLY, LandenC J, KamatAA, et al.. Preoperative serum tissue factor levels are an independent prognostic factor in patients with ovarian carcinoma. J Clin Oncol, 2006, 24(5): 755-761

[50]

SherrCJ. Cancer cell cycles. Science, 1996, 274(5293): 1672-1677

[51]

JanostiakR, RauniyarN, LamTT, et al.. MELK Promotes Melanoma Growth by Stimulating the NF-kappaB Pathway. Cell Rep, 2017, 21(10): 2829-2841

[52]

SpeersC, ZhaoSG, KothariV, et al.. Maternal Embryonic Leucine Zipper Kinase (MELK) as a Novel Mediator and Biomarker of Radioresistance in Human Breast Cancer. Clin Cancer Res, 2016, 22(23): 5864-5875

[53]

BarradasM, GonosES, ZebedeeZ, et al.. Identification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence. Exp Cell Res, 2002, 273(2): 127-137

[54]

ChengZ, GuoJ, ChenL, et al.. Overexpression of TMEM158 contributes to ovarian carcinogenesis. J Exp Clin Cancer Res, 2015, 34: 75

[55]

MohammedAES, EguchiH, WadaS, et al.. TMEM158 and FBLP1 as novel marker genes of cisplatin sensitivity in non-small cell lung cancer cells. Exp Lung Res, 2012, 38(9–10): 463-474

[56]

IglesiasD, Fernandez-PeraltaAM, NejdaN, et al.. RIS1, a gene with trinucleotide repeats, is a target in the mutator pathway of colorectal carcinogenesis. Cancer Genet Cytogenet, 2006, 167(2): 138-144

[57]

LiR, MacnamaraLM, LeuchterJD, et al.. MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery. Int J Mol Sci, 2015, 16(7): 15872-15902

[58]

MaY, HendershotLM. The role of the unfolded protein response in tumour development: friend or foe?. Nat Rev Cancer, 2004, 4(12): 966-977

[59]

KaufmanRJ. Orchestrating the unfolded protein response in health and disease. J Clin Invest, 2002, 110(10): 1389-1398

AI Summary AI Mindmap
PDF

112

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/