张琳梅,高岭,李少明,陈诚
ZHANG Linmei,GAO Lin,LI Shaoming,CHEN Cheng

• 1:西安医学院口腔医学院
• 2:青岛大学附属医院口腔颌面外科
• 3:西安交通大学口腔医院口腔综合科

摘要(Abstract)：

目的:探讨口腔鳞状细胞癌(OSCC)组织中冷诱导RNA结合蛋白(CIRP)和Toll样受体4(TLR4)的表达与患者临床病理特征及预后的关系。方法:选取确诊的40例OSCC患者癌组织标本作为研究组、瘤周正常组织作为对照组;收集患者的临床病理特征,采用免疫组织化学染色检测CIRP和TLR4蛋白的表达;电话随访患者或其家属,收集死亡患者的生存时间,采用Kaplan-Meier法分析死亡患者CIRP和TLR4表达对预后的影响。结果:研究组CIRP和TLR4蛋白阳性检出率均明显高于对照组,差异均有高度统计学意义(P<0.01);癌组织CIRP蛋白高、低表达组的患者TNM分期、临床分期、组织病理学分期及淋巴结转移的差异均有统计学意义(P<0.05),癌组织TLR4高、低表达组患者的性别、TMN分期、临床分期、组织病理学分级以及淋巴结转移的差异均有统计学意义(P<0.05);随访结果显示,癌组织CIRP高表达患者术后的生存率明显低于低表达患者(χ~2=6.651,P=0.009),癌组织TLR4高表达患者术后的生存率明显低于TLR4低表达患者(χ~2=8.473,P=0.004)。结论:CIRP与TLR4在OSCC癌组织中呈高表达,并与患者TNM分期、临床分期、组织病理学分期、淋巴结转移以及较差的生存率有关联。
Objective: To investigate the expression of cold induced RNA combined protein(CIRP) and Toll-like receptor 4(TLR4) of oral squamous cell carcinoma(OSCC) and its relationship with clinic-pathological features and prognosis. Methods: Selecting 40 cases of OSCC patients sample as experiment group, peritumoral-normal tissue as control group; collecting clinic-pathological features of patients, adopting Immunohistochemical staining to evaluate the expression of CIRP and TLR4; phone call follow-up on patients or family to collect survival time of deceased patients. Adopting Kaplan-Meier assay to analyze effect of CIRP and TLR4 of deceased patients on prognosis. Results: The positive detection rate of CIRP and TLR 4 in the experiment group was higher than that of the control group, differences were highly statistically significant(P<0.01); the differences of TNM staging, clinical staging, histopathological staging and lymph node metastasis of of CIRP protein high and low expression groups were statistically significant(P<0.05); the differences of gender, TNM staging, clinical staging, histopathological staging and lymph node metastasis of of TLR4 high and low expression groups were statistically significant(P<0.05). The overall survival rate of patients with high CIRP expression was lower than that of patients with low expression(χ~2=6.651,P=0.009), overall survival rate of patients with high TLR4 expression was lower than that of patients with low expression(χ~2=8.473,P=0.004). Conclusion: CIRP and TLR4 showed high expression in OSCC patients, which was correlated with TNM staging, clinical staging, histopathological staging and lymph node metastasis as well as poor survival rate.

关键词(KeyWords)： Toll样受体4;口腔鳞状细胞癌;免疫组织化学;病理学,临床;冷诱导RNA结合蛋白;肿瘤预后
toll-like receptor 4;oral squamous cell carcinoma;immunohistochemistry;pathology,clinical;cold inducible RNA binding protein;prognosis

Abstract:

Keywords:

基金项目(Foundation): 陕西省教委基金(19JK0764)

作者(Author): 张琳梅,高岭,李少明,陈诚
ZHANG Linmei,GAO Lin,LI Shaoming,CHEN Cheng

DOI: 10.19367/j.cnki.1000-2707.2020.01.018

参考文献(References)：

• [1] LAMM D L.Cancer statistics[J].Ca A Cancer Journal for Clinicians,2010,40(5):318-319.
• [2] FUNK G,KARNELL L H,ROBINSON R,et al.Presentation,treatment,and outcome of oral cavity Cancer:A national cancer data base report[J].Head & Neck,2002,24(2):165-180.
• [3] PAVLOVA N N,THOMPSON C B.The emerging hallmarks of cancer metabolism[J].Cell Metabolism,2016,23(1):27-47.
• [4] JOSE B,GRACIA S,YOLANDA J.Oral Cancer:clinical features[J].Oral Oncology,2010,46(6):414-417.
• [5] TANG A T,CHOI J P,KOTZIN J J,et al.Endothelial TLR4 and the microbiome drive cerebral cavernous malformations[J].Nature,2017,545(7654):305.
• [6] YEH D W,HUANG L R,CHEN Y W,et al.Interplay between inflammation and stemness in cancer cells:the role of toll-Like receptor signaling[J].Journal of Immunology Research,2016,2016(6):1-14.
• [7] KHAN M M,YANG W L,BRENNER M,et al.Cold-inducible RNA-binding protein (CIRP) causes sepsis-associated acute lung injury via induction of endoplasmic reticulum stress[J].Scientific Reports,2017,7:41363.
• [8] QIANG X,YANG W L,WU R,et al.Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis[J].Nature Medicine,2013,19(11):1489.
• [9] JANG H H,LEE H N,KIM S Y,et al.Expression of RNA-binding Motif Protein 3 (RBM3) and Cold-inducible RNA-binding protein (CIRP) is associated with improved clinical outcome in patients with colon cancer[J].Anticancer Research,2017,37(4):1779-1785.
• [10]MALUMBRE S,MARCO S.Cyclin-dependent kinases[J].Genome Biology,2014,15(6):122.
• [11]陈志英,何常,朱璐宏.食管鳞癌细胞中程序性细胞死亡因子4与核转录因子的表达[J].贵州医科大学学报,2018,43(9):1042-1045,1054.
• [12]GOSWAMI K K,GHOSH T,GHOSH S,et al.Tumor promoting role of anti-tumor macrophages in tumor microenvironment[J].Cellular Immunology,2017,316:1-10.
• [13]於宇,崔久嵬.从肿瘤微环境角度解析肿瘤免疫治疗的现状与未来[J].中国肿瘤生物治疗杂志,2017,24(7):693-699.
• [14]LEE H W,CHOI H J,HA S J,et al.Recruitment of monocytes/macrophages in different tumor microenvironments[J].Biochimica Et biophysica Acta,2013,1835(2):170-179.
• [15]YOSHIMURA T.The production of monocyte chemoattractant protein-1 (MCP-1)/CCL2 in tumor microenvironments[J].Cytokine,2017,98:71-78.
• [16]BARRY K C,HSU J,BROZ M L,et al.A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments[J].Nature Medicine,2018,24(8):1178-1191.
• [17]YU Z,PRAKASH K,TAKAHIRO I,et al.Down-regulating cold shock protein genes impairs cancer cell survival and enhances chemosensitivity[J].Journal of Cellular Biochemistry,2010,107(1):179-188.
• [18]TANG Z H,PENG J,REN Z,et al.New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-κB pathway[J].Atherosclerosis,2017,262:113.
• [19]YIN H,HUANG L,OUYANG T,et al.Baicalein improves liver inflammation in diabetic db/db mice by regulating HMGB1/TLR4/NF-κB signaling pathway[J].International Immunopharmacology,2018,55:55-62.
• [20]WANG W,ZHAN E,YU Y,et al.MiR-216a exerts tumor-suppressing functions in renal cell carcinoma by targeting TLR4[J].American Journal of Cancer Research,2018,8(3):476.
• [21]CHANG Z L.Important aspects of Toll-like receptors,ligands and their signaling pathways[J].Inflammation Research,2010,59(10):791-808.
• [22]KELLY M G,ALVERO A B,RUI C,et al.TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer[J].Cancer Research,2006,66(7):3859.
• [23]MOLTENI M,MARABELLA D,ORLANDII C,et al.Melanoma cell lines are responsive in vitro to lipopolysaccharide and express TLR-4[J].Cancer Letters,2006,235(1):75-83.
• [24]GUOXIN R,JINGZHOU H,RUNXIANG W,et al.Rapamycin inhibits Toll-like receptor 4-induced pro-oncogenic function in head and neck squamous cell carcinoma[J].Oncology Reports,2014,31(6):2804.
• [25]张海涛,薛菁晖,张志文.冷休克蛋白与肿瘤的研究进展[J].中华临床医师杂志(电子版),2013,7(5):151-152.
• [26]ANA A C,CALLEJAS F B,JOSEP C,et al.Cold-inducible RNA-binding protein bypasses replicative senescence in primary cells through extracellular signal-regulated kinase 1 and 2 activation[J].Molecular & Cellular Biology,2009,29(7):1855.
• [27]WANG A C,SU Q B,WU F X,et al.Role of TLR4 for paclitaxel chemotherapy in human epithelial ovarian cancer cells[J].European Journal of Clinical Investigation,2010,39(2):157-164.

文章评论(Comment)：