|Table of Contents|

Expression of CST6 in thyroid papillary carcinoma and its effect on cell biological function

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

Issue:
2024 22
Page:
4235-4244
Research Field:
Publishing date:

Info

Title:
Expression of CST6 in thyroid papillary carcinoma and its effect on cell biological function
Author(s):
HU Jinbo1ZHANG Lu2NIU Haigang13GUO Wenke3TIAN Xiaoai3GUO Jianping3
1.Fenyang College of Shanxi Medical University,Shanxi Lvliang 032200,China;2.Affiliated Hospital of Hebei University,Hebei Baoding 071000,China;3.Fenyang Hospital,Shanxi Province,Shanxi Lvliang 032200,China.
Keywords:
cysteine protease inhibitory factor 6papillary thyroid carcinomacervical lymph node metastasisepithelial-mesenchymal transition
PACS:
R736.1
DOI:
10.3969/j.issn.1672-4992.2024.22.004
Abstract:
Objective:To study the expression of cysteine protease inhibitory factor 6 (Cystatin M/E,Cystatin 6,CST6) in papillary thyroid carcinoma (PTC) and its correlation with cervical lymph node metastasis,and the relationship between the expression of CST6 and the malignant biological behavior of PTC cells,and initially explore its pathway.relationship between CST6 expression and the malignant biological behavior of PTC cells,and preliminarily explore its pathway of action.Methods:119 PTC patients were selected,and immunohistochemistry was applied to detect CST6 protein expression in PTC and thyroid follicular epithelial tissues,and the protein expression level of CST6 was detected by RT-qPCR and Western Blot in human papillary thyroid carcinoma cell lines TPC-1,K1,and B-CPAP,as well as in human thyroid normal cell line Nthy-ori 3-1.CST6 overexpressing and interfering cell lines were screened and constructed according to the expression status,and changes in the invasion and migration ability of PTC cells were determined by Transwell and Wound-Healing assays.The change trend of key proteins (E-cadherin,N-cadherin,Vimentin) in epithelial-mesenchymal transition (EMT) was detected by Western Blot.Results:Compared with normal thyroid tissues,CST6 was expressed at a lower level in PTC tissues,and CST6 was highly expressed in the follicular epithelium of the thyroid gland of patients with pN1 versus those of thyroid cancer tissues of patients with pN0.The expression level of CST6 was correlated with the length of the tumor diameter (P<0.000 1) as well as with the metastasis of the cervical lymph nodes (P<0.000 3).Compared with the OE-CST6 group,the sh-CST6 group had a stronger trend of invasion and migration.Meanwhile,E-cadherin protein expression was significantly down-regulated and N-cadherin and Vimentin protein expression was significantly up-regulated in sh-CST6 group (P<0.05).Conclusion:CST6,as a protective factor,was lowly expressed in PTC,and its expression degree was correlated with lymph node metastasis.Overexpression of CST6 protein could inhibit the migration and invasion ability of PTC cells,as well as reduce cervical lymph node metastasis caused by the trans-epithelial-mesenchymal transition pathway.

References:

[1] 王少明,郑荣寿,韩冰峰,等.2022年中国人群恶性肿瘤发病与死亡年龄特征分析 [J/OL].中国肿瘤,1-10[2024-03-16].http://kns.cnki.net/kcms/detail/11.2859.R.20240311.0800.002.html. WANG SM,ZHENG RS,HAN BF,et al.Analysis of age characteristics of malignant tumor incidence and death in Chinese population in 2022 [J/OL].China Tumor,1-10[2024-03-16].http://kns.cnki.net/kcms/detail/11.2859.R.20240311.0800.002.html.
[2] ZHENG R,ZHANG S,ZENG H,et al.Cancer incidence and mortality in China,2016 [J].Journal of the National Cancer Center,2022,2(1):1-9.
[3] 赫捷,李进,程颖,等.中国临床肿瘤学会(CSCO)分化型甲状腺癌诊疗指南2021 [J].肿瘤预防与治疗,2021,34(12):1164-1201. HE J,LI J,CHENG Y,et al.Chinese Society of Clinical Oncology (CSCO) Guidelines for the treatment of differentiated thyroid cancer 2021 [J].Tumor Prevention and Therapy,2021,34(12):1164-1201.
[4] BIBLE KC,KEBEBEW E,BRIERLEY J,et al.2021 American Thyroid Association Guidelines for management of patients with anaplastic thyroid cancer [J].Thyroid,2021,31(3):337-386.
[5] SUGITANI I,ITO Y,TAKEUCHI D,et al.Indications and strategy for active surveillance of adult low-risk papillary thyroid microcarcinoma:consensus statements from the Japan association of endocrine surgery task force on management for papillary thyroid microcarcinoma [J].Thyroid,2021,31(2):183-192.
[6] 袁欣越,姚瑶,程帅,等.单侧甲状腺乳头状癌对侧淋巴结转移高危因素的临床研究 [J].中国癌症杂志,2023,33(06):619-628. YUAN XY,YAO Y,CHENG S,et al.Clinical study of risk factors for contralateral lymph node metastasis in unilateral papillary thyroid cancer [J].Chinese Journal of Cancer,2023,33(06):619-628.
[7] 徐震纲,刘绍严.分化型甲状腺癌颈侧区淋巴结清扫专家共识(2017版) [J].中国实用外科杂志,2017,37(09):985-991. XU ZG,LIU SY.Expert consensus on lymph node dissection in the lateral neck region of differentiated thyroid cancer (2017 edition) [J].Chinese Journal of Practical Surgery,2017,37(09):985-991.
[8] 高明,葛明华,嵇庆海,等.甲状腺微小乳头状癌诊断与治疗中国专家共识(2016版) [J].中国肿瘤临床,2016,43(10):405-411. GAO M,GE MH,JI QH,et al.Chinese expert consensus on diagnosis and treatment of micropapillary thyroid cancer (2016 edition) [J].China Cancer Clinics,2016,43(10):405-411.
[9] 刘世强,叶钿均,蒋殿虎,等.TNM分期年龄组别cN0期甲状腺乳头状癌中央区淋巴结转移的差异分析 [J].临床外科杂志,2017,25(11):849-851. LIU SQ,YE DJ,JIANG DH,et al.Differential analysis of central regional lymph node metastasis in cN0 stage papillary thyroid cancer by TNM staging age group [J].Journal of Clinical Surgery,2017,25(11):849-851.
[10] 张伯豪.示踪用盐酸米托蒽醌注射液在甲状腺癌手术中的临床应用 [D].石家庄:河北医科大学,2022. ZHANG BH.Clinical application of tracer mitoxantrone hydrochloride injection in thyroid cancer surgery [D].Shijiazhuang:Hebei Medical University,2022.
[11] 顾建华,程宇,于娟,等.示踪用盐酸米托蒽醌注射液对甲状腺癌前哨淋巴结示踪疗效及对甲状旁腺功能的保护作用研究 [J].中国临床药理学杂志,2022,38(20):2392-2395. GU JH,CHENG Y,YU J,et al.Efficacy of mitoxantrone hydrochloride injection for tracing sentinel lymph nodes of thyroid cancer and its protective effect on parathyroid function [J].Chinese Journal of Clinical Pharmacology,2022,38(20):2392-2395.
[12] LALMANACH G,KASABOVA-ARJOMAND M,LECAILLE F,et al.Cystatin M/E (Cystatin 6):A Janus-Faced cysteine protease inhibitor with both tumor-suppressing and tumor-promoting functions [J].Cancers (Basel),2021,13(8):1877.
[13] SOTIROPOULOU G,ANISOWICZ A,SAGER R.Identification,cloning,and characterization of cystatin M,a novel cysteine proteinase inhibitor,down-regulated in breast cancer [J].J Biol Chem,1997,272(2):903-910.
[14] XU D,DING S,CAO M,et al.A Pan-cancer analysis of Cystatin E/M reveals its dual functional effects and positive regulation of epithelial cell in human tumors [J].Front Genet,2021,12:733211.
[15] WALLIN H,APELQVIST J,ANDERSSON F,et al.Low-level internalization of cystatin E/M affects legumain activity and migration of melanoma cells [J].J Biol Chem,2017,292(35):14413-14424.
[16] HOSOKAWA M,KASHIWAYA K,EGUCHI H,et al.Over-expression of cysteine proteinase inhibitor cystatin 6 promotes pancreatic cancer growth [J].Cancer Sci,2008,99(8):1626-1632.
[17] 吴翠翠,张雪琦,吴志坚.miR-145在甲状腺乳头状癌组织中表达及其对淋巴结转移和预后的预测价值 [J].中国老年学杂志,2024,44(04):786-789. WU CC,ZHANG XQ,WU ZJ.Expression of miR-145 in papillary thyroid cancer tissues and its predictive value for lymph node metastasis and prognosis [J].Chinese Journal of Gerontology,2024,44(04):786-789.
[18] 李子垚,张海平,买地尼也提·尼亚孜,等.Cystatin 6蛋白在哈萨克族食管鳞癌组织中的表达及其意义 [J].癌变·畸变·突变,2022,34(06):429-433,438. LI ZY,ZHANG HP,BAYDINYETI NYZ,et al.Expression of Cystatin 6 protein in Kazakh esophageal squamous carcinoma tissues and its significance [J].Cancer-Mutations-Mutations,2022,34(06):429-433,438.
[19] OLER G,CAMACHO CP,HOJAIJ FC,et al.Gene expression profiling of papillary thyroid carcinoma identifies transcripts correlated with BRAF mutational status and lymph node metastasis [J].Clin Cancer Res,2008,14(15):4735-4742.
[20] UHLEN M,FAGERBERG L,HALLSTROM BM,et al.Proteomics.Tissue-based map of the human proteome [J].Science,2015,347(6220):1260419.
[21] REN H,ZHANG Q,BAO L,et al.CST6 promotes the aggressive phenotype of thyroid cancer through maintaining autophagy [EB/OL].https://doi.org/10.21203/rs.3.rs-2959472/v1.2023-05-26.
[22] YU T,TONG L,AO Y,et al.Novel design of NIR-triggered plasmonic nanodots capped mesoporous silica nanoparticles loaded with natural capsaicin to inhibition of metastasis of human papillary thyroid carcinoma B-CPAP cells in thyroid cancer chemo-photothermal therapy [J].J Photochem Photobiol B,2019,197:111534.
[23] JIN L,ZHANG Y,LI H,et al.Differential secretome analysis reveals CST6 as a suppressor of breast cancer bone metastasis [J].Cell Res,2012,22(9):1356-1373.
[24] SCHAGDARSURENGIN U,PFEIFER GP,DAMMANN R.Frequent epigenetic inactivation of cystatin M in breast carcinoma [J].Oncogene,2007,26(21):3089-3094.
[25] PULUKURI SM,GORANTLA B,KNOST JA,et al.Frequent loss of cystatin E/M expression implicated in the progression of prostate cancer [J].Oncogene,2009,28(31):2829-2838.
[26] 田原,聂鑫,胡飞环,等.抑癌基因CST6及其异常甲基化后在肿瘤发生中的意义 [J].分子诊断与治疗杂志,2013,5(04):268-273. TIAN Y,NIE X,HU FH,et al.Significance of oncogene CST6 and its aberrant methylation in tumorigenesis [J].Journal of Molecular Diagnosis and Therapy,2013,5(04):268-273.
[27] BENEZEDER T,TIRAN V,TREITLER AAN,et al.Multigene methylation analysis of enriched circulating tumor cells associates with poor progression-free survival in metastatic breast cancer patients [J].Oncotarget,2017,8(54):92483-92496.
[28] CHIMONIDOU M,TZITZIRA A,STRATI A,et al.CST6 promoter methylation in circulating cell-free DNA of breast cancer patients [J].Clin Biochem,2013,46(3):235-240.
[29] PAOLILLO M,SCHINELLI S.Extracellular matrix alterations in metastatic processes [J].Int J Mol Sci,2019,20(19):4947.
[30] MITROVIC A,MIRKOVIC B,SOSIC I,et al.Inhibition of endopeptidase and exopeptidase activity of cathepsin B impairs extracellular matrix degradation and tumour invasion [J].Biol Chem,2016,397(2):165-174.

Memo

Memo:
山西省吕梁市重点研发项目(编号:2020SHFZ63);山西省汾阳医院科技攻关项目(编号:202305)
Last Update: 1900-01-01