|Table of Contents|

Identification of hub genes related to lymph node metastasis and distant metastasis in papillary thyroid carcinoma by weighted gene co-expression network analysis

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2022 03
Page:
429-435
Research Field:
Publishing date:

Info

Title:
Identification of hub genes related to lymph node metastasis and distant metastasis in papillary thyroid carcinoma by weighted gene co-expression network analysis
Author(s):
GUO Mingyue; WANG Lidong; HUANG Yonglian; LIU Chenxi; TAN Hao; LIU Zhen
Department of General Surgery,Shengjing Hospital of China Medical University,Liaoning Shenyang 110022,China.
Keywords:
papillary thyroid carcinoma; weighted gene co-expression network analysis; hub gene; lymph node metastasis; distant metastasis
PACS:
R736.1
DOI:
10.3969/j.issn.1672-4992.2022.03.012
Abstract:
Objective:To idnetificate of hub genes related to lymph nodes metastasis and distant metastasis in papillary thyroid carcinoma.Methods:We used weighted gene co-expression network analysis(WGCNA) to construct a co-expression network for tumor expression profile,and the candidate core genes with the highest correlation with PTC lymph node metastasis and distant metastasis were screened.The data of GSE3678 database，the Oncomine database and 86 PTC specimens was used to validate and the correlation between these genes and clinicopathological characteristics was analyzed.Results:Six core genes related to lymph node metastasis(CLDN1,COL8A1,COL8A2,IL1RAP,LPAR5 and GPC3) and three core genes closely related to PTC distant metastasis(LAMA2,GPC3 and CCL17) were identified.Verification by PTC and paracancillary tissues showed that the expression of CLDN1,COL8A1,COL8A2,IL1RAP and LPAR5 were significantly higher in PTC,while the expression of GPC3 was significantly lower in PTC,and all of them were closely correlated with cervical lymph node metastasis(P＜0.05).In addition,the expression of LPAR5 was higher in tumor>2 cm PTC,while the expression of GPC3 was lower in bilateral PTC(P＜0.05).Conclusion:This research provides some potential gene targets for the diagnosis and treatment of PTC by WGCNA to screened the core genes closely related to PTC lymph node metastasis and distant metastasis,which shows a new direction for the study of molecular mechanisms related to metastasis of PTC.

References:

[1]SEIB CD,SOSA JA.Evolving understanding of the epidemiology of thyroid cancer［J］.Endocrinol Metab Clin North Am,2019,48(1):23-35.
[2]XU C,WANG Y,YANG H,et al.Association between cancer incidence and mortality in web-based data in China:Infodemiology study［J］.Journal of Medical Internet Research,2019,21(1):e10677.
[3] DOU Yi, HU Daixing,CHEN Yingji,et al.PTC located in the upper pole is more prone to lateral lymph node metastasis and skip metastasis［J］.World J Surg Oncol,2020,18(1):188.
[4] HU Jianxia,LI Chengqian,LIU Chongkai,et al.Expressions of miRNAs in papillary thyroid carcinoma and their associations with the clinical characteristics of PTC［J］.Cancer Biomark,2017,18(1):87-94.
[5] SMITH VA,SESSIONS RB,LENTSCH EJ.Cervical lymph node metastasis and papillary thyroid carcinoma:does the compartment involved affect survival? Experience from the SEER database［J］.J Surg Oncol,2012,106(4):357-362.
[6] LIU Tongtong,ZHOU Shichong,YU Jinhua,et al.Prediction of lymph node metastasis in patients with papillary thyroid carcinoma:A radiomics method based on preoperative ultrasound images［J］.Technol Cancer Res Treat,2019,1:18.
[7]KAMPO S,AHMMED B,ZHOU T,et al.Scorpion venom analgesic peptide,bmK AGAP inhibits stemness,and epithelial-mesenchymal transition by down-regulating PTX3 in breast cancer［J］.Front Oncol,2019,9:21.
[8]PARK H,PARK J,PARK SY,et al.Clinical course from diagnosis to death in patients with well-differentiated thyroid cancer［J］.Cancers,2020,12(8):2323.
[9]LUO Y,COSKUN V,LIANG A,et al.Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells［J］.Cell,2015,161(5):1175-1186.
[10]TSUDA T.Extracellular interactions between fibulins and transforming growth factor(TGF)-beta in physiological and pathological conditions［J］.Int J Mol Sci,2018,19(9):2787.
[11]YOKO KATSUNO DSM,ZHANG Ziyang.Chronic TGF-b exposure drives stabilized EMT,tumor stemness,and cancer drug resistance with vulnerability to bitopic mTOR inhibition［J］.Cancer,2019,12(570):8544.
[12]GARCIA-RENDUELES AR,RODRIGUES JS,GARCIA-RENDUELES ME,et al.Rewiring of the apoptotic TGF-beta-SMAD/NFkappaB pathway through an oncogenic function of p27 in human papillary thyroid cancer［J］.Oncogene,2017,36(5):652-666.
[13]GUO X,XIAO H,GUO S,et al.Identification of breast cancer mechanism based on weighted gene coexpression network analysis［J］.Cancer Gene Ther,2017,24(8):333-341.
[14] MA Xianxiong,TAO Ruikang,LI Lei,et al.Identification of a 5 microRNA signature and hub miRNA mRNA interactions associated with pancreatic cancer［J］.Oncol Rep,2019,41(1):292-300.
[15]GUO L,ZHANG K,BING Z.Application of a coexpression network for the analysis of aggressive and nonaggressive breast cancer cell lines to predict the clinical outcome of patients［J］.Mol Med Rep,2017,16(6):7967-7978.
[16]WETTENHALL JM,SIMPSON KM,SATTERLEY K,et al.affylmGUI:a graphical user interface for linear modeling of single channel microarray data［J］.Bioinformatic,2006,22(7):897-899.
[17]NEMETH J,NEMETH Z,TATRAI P,et al.High expression of claudin-1 protein in papillary thyroid tumor and its regional lymph node metastasis［J］.Pathol Oncol Res,2010,16(1):19-27.
[18]CHANG TLI,KOSEI,TUN KIAT,et al.Claudin-1 has tumor suppressive activity and is a direct target of RUNX3 in gastric epithelial cells［J］.Gastroenterology,2010,138(1):255-265.
[19] FENG Siyang,ZHAI Jianxue,LU Di,et al.TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by upregulating claudin-1 in non-small-cell lung cancer cells［J］. Exp Cell Res,2018,373(1-2):44-56.
[20] ABDERRAHMAN OUBAN.Claudin-1 role in colon cancer:An update and a review［J］.Histol Histopathol,2018,33(10):1013-1019.
[21] FARUK TAS,ELIF BILGIN,KAYHAN ERTURK,et al.Clinical significance of serum claudin-1 levels in melanoma patients［J］.Melanoma Res,2016,26(4):377-381.
[22] WU JE,WU YY,TUNG CH,et al.DNA methylation maintains the CLDN1-EPHB6-SLUG axis to enhance chemotherapeutic efficacy and inhibit lung cancer progression［J］.Theranostics,2020,10(19):8903-8923.
[23]HWANG JS,MA DJ,CHOI J,et al.COL8A2 regulates the fate of corneal endothelial cells［J］.Invest Ophthalmol Vis Sci,2020,61(11):26.
[24]LI X,WANG Z,TONG H,et al.Effects of COL8A1 on the proliferation of muscle-derived satellite cells［J］.Cell Biol Int,2018,42(9):1132-1140.
[25]SHANG J,WANG F,CHEN P,et al.Co-expression network analysis identified COL8A1 is associated with the progression and prognosis in human colon adenocarcinoma［J］.Dig Dis Sci,2018,63(5):1219-1228.
[26]SUBRAMANIAM S,STANSBERG C,CUNNINGHAM C.The interleukin 1 receptor family［J］.Dev Comp Immunol,2004,28(5):415-428.
[27]AGERSTAM H,KARLSSON C,HANSEN N,et al.Antibodies targeting human IL1RAP(IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia［J］.Proc Natl Acad Sci USA,2015,112(34):10786-10791.
[28]MITCHELL K,BARREYRO L,TODOROVA TI,et al.IL1RAP potentiates multiple oncogenic signaling pathways in AML［J］.J Exp Med,2018,215(6):1709-17027.
[29]AGERSTAM H,HANSEN N,VON PALFFY S,et al.IL1RAP antibodies block IL-1-induced expansion of candidate CML stem cells and mediate cell killing in xenograft models［J］.Blood,2016,128(23):2683-2693.
[30]SMALLRIDGE RC,CHINDRIS AM,ASMANN YW,et al.RNA sequencing identifies multiple fusion transcripts,differentially expressed genes,and reduced expression of immune function genes in BRAF(V600E) mutant vs BRAF wild-type papillary thyroid carcinoma［J］.J Clin Endocrinol Metab,2014,99(2):E338-347.
[31]LIN ME,RIVERA RR,CHUN J.Targeted deletion of LPA5 identifies novel roles for lysophosphatidic acid signaling in development of neuropathic pain［J］.J Biol Chem,2012,287(21):17608-17617.
[32]ZHOU Y,LITTLE PJ,CAO Y,et al.Lysophosphatidic acid receptor 5 transactivation of TGFBR1 stimulates the mRNA expression of proteoglycan synthesizing genes XYLT1 and CHST3［J］.Biochim Biophys Acta Mol Cell Res,2020,1867(12):118848.
[33]PLASTIRA I,BERNHART E,GOERITZER M,et al.1-Oleyl-lysophosphatidic acid(LPA) promotes polarization of BV-2 and primary murine microglia towards an M1-like phenotype［J］.J Neuroinflammation,2016,13(1):205.
[34]ZHENG YQ,HU MF.Trichostatin A alleviates the process of breast carcinoma by downregulating LPAR5［J］.European Review for Medical and Pharmacological Sciences,2020,24:6417-6425.
[35]WU CY,ZHENG C,XIA EJ,et al.Lysophosphatidic acid receptor 5(LPAR5) plays a significance role in papillary thyroid cancer via phosphatidylinositol 3-Kinase/Akt/mammalian target of rapamycin(mTOR) pathway［J］.Med Sci Monit,2020,26:e919820.
[36]SCHIRWANI S,NOVELLI A,DIGILIO MC,et al.Duplications of GPC3 and GPC4 genes in Symptomatic female carriers of simpson-Golabi-Behmel syndrome type 1［J］.Eur J Med Genet,2019,62(4):243-247.
[37]MICHAEL V,ORTIZ SSR,JULIA GLADE BENDER,et al.Immunotherapeutic targeting of GPC3 in pediatric solid embryonal tumors［J］.Frontiers in Oncology,2019,9:108.
[38]VUILLAUME ML,MOIZARD MP,HAMMOUCHE E,et al.Are all Xq26.2 duplications overlapping GPC3 on array-CGH a cause of Simpson-Golabi-Behmel syndrome? When do we need transcript analysis［J］.Clin Genet,2018,93(5):1111-1113.
[39]RAHBARI M,PECQUEUX M,AUST D,et al.Expression of glypican 3 is an independent prognostic biomarker in primary gastro-esophageal adenocarcinoma and corresponding serum exosomes［J］.J Clin Med,2019,8(5):696.
[40]FEI X,ZHANG J,ZHAO Y,et al.miR-96 promotes invasion and metastasis by targeting GPC3 in non-small cell lung cancer cells［J］.Oncol Lett,2018,15(6):9081-9086.
[41]FU Y,URBAN DJ,NANI RR,et al.Glypican-3-specific antibody drug conjugates targeting hepatocellular carcinoma［J］.Hepatology,2019,70(2):563-576.
[42]刘钊,田宇航, 孙一欣, 等. GPC3作为肝癌预后指标和免疫治疗新靶点的研究进展［J］.现代肿瘤医学，2017,25(18):3000-3004. LIU Zhao,TIAN Yuhang,SUN Yixin,et al.The research progress of GPC3 as a prognostic index and promising immunotherapy target for hepatocellular carcinoma［J］.Modern Oncology,2017,25(18):3000-3004.
[43]FERNANDEZ D,GUERENO M,LAGO HUVELLE MA,et al.Signaling network involved in the GPC3-induced inhibition of breast cancer progression:role of canonical Wnt pathway［J］.J Cancer Res Clin Oncol,2018,144(12):2399-2418.
[44]PLATEROTI M,ROSIGNOLO F,SPONZIELLO M,et al.Expression of PAX8 target genes in papillary thyroid carcinoma［J］.PLoS One,2016,11(6):e0156658.

Memo

Memo:
National Natural Science Foundation of China(No.81672644）；国家自然科学基金（编号：81672644）
Last Update: 2021-12-31