HMGB1和HIF1a在乳头状甲状腺癌中的表达及意义
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摘要
目的探讨高迁移率族蛋白1(HMGB1)和缺氧诱导因子1a(HIF1a)在乳头状甲状腺癌(PTC)中的表达及与临床病理特征的关系。方法采用免疫组织化学法检测120对PTC(肿瘤组)及其相应癌旁组织(非癌组织组)中HMGB1与HIF1a的表达,比较两组HMGB1与HIF1a蛋白表达的差异,并分析其表达水平与PTC患者临床病理特征的关系。结果 PTC组织中HMGB1阳性表达率高于癌旁组织(P<0.05);PTC组织中HIF1a阳性表达率高于癌旁组织(P<0.05)。PTC组织中HMGB1与HIF1a的表达呈正相关(P<0.05)。HIF1a和HMGB1在不同肿瘤直径、肿瘤数量、淋巴结转移情况及临床分期比较,差异有统计学意义(P <0.05)结论 HMGB1、HIF1a与PTC增殖和转移相关,可能是PTC发生、发展的重要分子,进一步研究两者的关系可能为抑制肿瘤增殖、转移提供潜在的分子靶点。
Objective To investigate the expression of high mobility group protein 1(HMGB1) and hypoxia inducible factor 1 A(HIF1 a) in papillary thyroid carcinoma and its significance. Methods The expression of HMGB1 and HIF1 a in 120 patients with papillary thyroid carcinoma(tumor group) and its corresponding para-cancerous tissue(non-cancerous tissue group) was detected by immunohistochemistry. The difference between the expression of HMGB1 and HIF1 a in the two groups was compared, and the relationship between the expression of the two groups and the pathological features of the patients with papillary thyroid carcinoma was analyzed. Results The positive expression rates of HMGB1 in PTC tissues and adjacent tissues were 65% and 35%, respectively. The difference was statistically significant by χ~2 test(χ~2= 8.067, P = 0.005), the positive expression rate of HMGB1 in PTC tissues was higher than that in adjacent tissues. The positive expression rates of HIF1 a in PTC tissues and adjacent tissues were59.2% and 40.8%, respectively. The positive expression rate of PTC was higher than that of adjacent tissues(χ~2= 9.6,P = 0.002). Correlation analysis showed that HMGB1 was positively correlated with HIF1 a expression in PTC tissues(r = 0.495, P = 0.014). The expression of HMGB1 in patients with different tumor sizes, tumor numbers, lymphatic metastases and clinical stages were statistical different(P < 0.05). Similarly, the high expression of HIF1 a was also significantly different from patients with different tumor size, tumor number, lymphatic metastasis and clinical stage(P < 0.05). There were significant differences in tumor size, tumor number, lymphatic metastasis and clinical stage(P < 0.05). Conclusions HMGB1 and HIF1 a are associated with proliferation and metastasis of papillary thyroid carcinoma. It may be an important molecule in the development of papillary thyroid carcinoma. The further study of the relationship may provide a potential molecular target for inhibiting tumor proliferation and metastasis.
Objective To investigate the expression of high mobility group protein 1(HMGB1) and hypoxia inducible factor 1 A(HIF1 a) in papillary thyroid carcinoma and its significance. Methods The expression of HMGB1 and HIF1 a in 120 patients with papillary thyroid carcinoma(tumor group) and its corresponding para-cancerous tissue(non-cancerous tissue group) was detected by immunohistochemistry. The difference between the expression of HMGB1 and HIF1 a in the two groups was compared, and the relationship between the expression of the two groups and the pathological features of the patients with papillary thyroid carcinoma was analyzed. Results The positive expression rates of HMGB1 in PTC tissues and adjacent tissues were 65% and 35%, respectively. The difference was statistically significant by χ~2 test(χ~2= 8.067, P = 0.005), the positive expression rate of HMGB1 in PTC tissues was higher than that in adjacent tissues. The positive expression rates of HIF1 a in PTC tissues and adjacent tissues were59.2% and 40.8%, respectively. The positive expression rate of PTC was higher than that of adjacent tissues(χ~2= 9.6,P = 0.002). Correlation analysis showed that HMGB1 was positively correlated with HIF1 a expression in PTC tissues(r = 0.495, P = 0.014). The expression of HMGB1 in patients with different tumor sizes, tumor numbers, lymphatic metastases and clinical stages were statistical different(P < 0.05). Similarly, the high expression of HIF1 a was also significantly different from patients with different tumor size, tumor number, lymphatic metastasis and clinical stage(P < 0.05). There were significant differences in tumor size, tumor number, lymphatic metastasis and clinical stage(P < 0.05). Conclusions HMGB1 and HIF1 a are associated with proliferation and metastasis of papillary thyroid carcinoma. It may be an important molecule in the development of papillary thyroid carcinoma. The further study of the relationship may provide a potential molecular target for inhibiting tumor proliferation and metastasis.
引文
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[15]VENEREAU E,de LEO F,MEZZAPELLE R,et al.HMGB1 as biomarker and drug target[J].Pharmacol Res,2016,111:534-544.
[16]QIU Y,CHEN Y,ZENG T,et al.High-mobility group box-B1(HMGB1)mediates the hypoxia-induced mesenchymal transition of osteoblast cells via activating ERK/JNK signaling[J].Cell Biol Int,2016,40(11):1152-1161.
[17]CHENG Y,XIONG J,CHEN Q,et al.Hypoxia/reoxygenationinduced HMGB1 translocation and release promotes islet proinflammatory cytokine production and early islet graft failure through TLRs signaling[J].Biochim Biophys Acta,2017,1863(2):354-364.
[2]LEE Y S,KIM Y,JEON S,et al.Cytologic,clinicopathologic,and molecular features of papillary thyroid carcinoma with prominent hobnail features:10 case reports and systematic literature review[J].Int J Clin Exp Pathol,2015,8(7):7988-7997.
[3]HUANG Y,LIN D,TANIGUCHI C M.Hypoxia inducible factor(HIF)in the tumor microenvironment:friend or foe[J].Sci China Life Sci,2017,60(10):1114-1124.
[4]REMMELE W,STEGNER H E.Recommendation for uniform definition of an immunoreactive score(IRS)for immunohistochemical estrogen receptor detection(ER-ICA)in breast cancer tissue[J].Pathologe,1987,8(3):138-140.
[5]ALMENDROS I,GOZAL D.Intermittent hypoxia and cancer:Undesirable bed partners[J].Respir Physiol Neurobiol,2018,256:79-86.
[6]MURUGESAN T,RAJAJEYABALACHANDRAN G,KUMARS,et al.Targeting HIF-2alpha as therapy for advanced cancers[J].Drug Discov Today,2018,23(7):1444-1451.
[7]QIN J,LIU Y,LU Y,et al.Hypoxia-inducible factor 1 alpha promotes cancer stem cells-like properties in human ovarian cancer cells by upregulating SIRT1 expression[J].Sci Rep,2017,7(1):DOI:10.1038/s41598-017-09244-8.
[8]TANG N N,ZHU H,ZHANG H J,et al.HIF-1alpha induces VE-cadherin expression and modulates vasculogenic mimicry in esophageal carcinoma cells[J].World J Gastroenterol,2014,20(47):17894-17904.
[9]LIU J,ZHANG C,ZHAO Y,et al.Parkin targets HIF-1alpha for ubiquitination and degradation to inhibit breast tumor progression[J].Nat Commun,2017,8(1):1823.
[10]LI X D,ZI H,FANG C,et al.Association between HIF1Ars11549465 polymorphism and risk of prostate cancer:a metaanalysis[J].Oncotarget,2017,8(27):44910-44916.
[11]ZHANG H,LU C,FANG M,et al.HIF-1alpha activates hypoxiainduced PFKFB4 expression in human bladder cancer cells[J].Biochem Biophys Res Commun,2016,476(3):146-152.
[12]WANG N,DONG C R,JIANG R,et al.Overexpression of HIF-1alpha,metallothionein and SLUG is associated with high TNM stage and lymph node metastasis in papillary thyroid carcinoma[J].Int J Clin Exp Pathol,2013,7(1):322-330.
[13]KOPEREK O,AKIN E,ASARI R,et al.Expression of hypoxiainducible factor 1 alpha in papillary thyroid carcinoma is associated with desmoplastic stromal reaction and lymph node metastasis[J].Virchows Arch,2013,463(6):795-802.
[14]TESAROVA P,KALOUSOVA M,ZIMA T,et al.HMGB1,S100proteins and other RAGE ligands in cancer-markers,mediators and putative therapeutic targets[J].Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub,2016,160(1):1-10.
[15]VENEREAU E,de LEO F,MEZZAPELLE R,et al.HMGB1 as biomarker and drug target[J].Pharmacol Res,2016,111:534-544.
[16]QIU Y,CHEN Y,ZENG T,et al.High-mobility group box-B1(HMGB1)mediates the hypoxia-induced mesenchymal transition of osteoblast cells via activating ERK/JNK signaling[J].Cell Biol Int,2016,40(11):1152-1161.
[17]CHENG Y,XIONG J,CHEN Q,et al.Hypoxia/reoxygenationinduced HMGB1 translocation and release promotes islet proinflammatory cytokine production and early islet graft failure through TLRs signaling[J].Biochim Biophys Acta,2017,1863(2):354-364.