B7-H1和B7-H4在口腔鳞状细胞癌组织中的表达及临床意义
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摘要
目的:探讨口腔鳞状细胞癌(Oral Squamous Cell Carcinoma,OSCC)中B7-H1和B7-H4的表达及其临床意义,并为OSCC的临床诊断、治疗、判断预后及预防等提供依据。方法:采用免疫组织化学S-P法检测B7-H1及B7-H4在60例OSCC及20例非肿瘤患者正常口腔黏膜组织(NOM)中的表达情况,分析两者与OSCC临床病理特征的相关性。结果:B7-H1在OSCC组织中表达显著高于在NOM组织中表达(29例,48.3%v4例,20%,x~2=4.969,P<0.05);B7-H4在OSCC组织中表达亦显著高于在NOM组织中表达(31例,51.7%v5例,25%,x~2=4.310,P<0.05)。B7-H1与B7-H4在OSCC组织的表达都与TNM分期、淋巴结转移和肿瘤分化程度显著相关(P<0.05),而与年龄、性别及肿瘤直径大小等无关。OSCC组织中B7-H1和B7-H4的高表达呈显著性正相关性(x~2=5.613 P<0.05),60例组织中B7-H1和B7-H4共表达现象有11例(18.3%),NOM中未发现两者共表达现象。结论:B7-H1和B7-H4过表达与OSCC发生、发展及预后有关,可以作为预后指标。
Objective: To explore the expression of B7-H1 and B7-H4 in Oral Squamous Cell Carcinoma(OSCC) and its clinical significance, and provide the basis for clinical diagnosis, treatment, prognosis and prevention of OSCC. Methods: Using immunohistochemical S-P method to detect B7-H1 and B7-H4 in 60 patients with OSCC and 20 cases of tumor expression innormal oral mucosa tissues(NOM), and the correlation with clinical pathological characteristics of OSCC are analyzed. Results: The expression ofB7-H1 in OSCC was significantly higher than that in the NOM group(29 cases, 48.3% v4, 20%, x~2=4.969, P<0.05). The expression of B7-H4 in OSCC was also significantly higher than that in the NOM group(31 cases, 51.7% v5, 25%, x~2=4.310, P<0.05). The expression of B7-H1 and B7-H4 in OSCC was significantly correlated with TNM staging, lymph node metastasis and tumor differentiation(P<0.05), regardless of age, sex and tumor diameter. The high expression of B7-H1 and B7-H4 in OSCC tissues showed significant positive correlation(x~2=5.613 P<0.05). There were 11 cases(18.3%) in the total expression of B7-H1 and B7-H4 in the 60 cases, and no common expression was found in NOM. Conclusion: B7-H1 and B7-H4 overexpression are associated with the occurrence, development and prognosis of OSCC,which can be used as prognostic indicators.
Objective: To explore the expression of B7-H1 and B7-H4 in Oral Squamous Cell Carcinoma(OSCC) and its clinical significance, and provide the basis for clinical diagnosis, treatment, prognosis and prevention of OSCC. Methods: Using immunohistochemical S-P method to detect B7-H1 and B7-H4 in 60 patients with OSCC and 20 cases of tumor expression innormal oral mucosa tissues(NOM), and the correlation with clinical pathological characteristics of OSCC are analyzed. Results: The expression ofB7-H1 in OSCC was significantly higher than that in the NOM group(29 cases, 48.3% v4, 20%, x~2=4.969, P<0.05). The expression of B7-H4 in OSCC was also significantly higher than that in the NOM group(31 cases, 51.7% v5, 25%, x~2=4.310, P<0.05). The expression of B7-H1 and B7-H4 in OSCC was significantly correlated with TNM staging, lymph node metastasis and tumor differentiation(P<0.05), regardless of age, sex and tumor diameter. The high expression of B7-H1 and B7-H4 in OSCC tissues showed significant positive correlation(x~2=5.613 P<0.05). There were 11 cases(18.3%) in the total expression of B7-H1 and B7-H4 in the 60 cases, and no common expression was found in NOM. Conclusion: B7-H1 and B7-H4 overexpression are associated with the occurrence, development and prognosis of OSCC,which can be used as prognostic indicators.
引文
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[2]Abadjian,MZ,Edwards,et al.Imaging,the Tumor Microenvironment[J].Advances in experimental medicine and biology,2017,1036:229-257
[3]Gee MH,Han A,Lofgren SM,et al.Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes[J].Cell,2017
[4]Luo Q,Ye J,Zeng L,et al.Elevated expression of PD-1 on T cells correlates with disease activity in rheumatoid arthritis[J].Molecularmedicine reports,2018,17(2):3297-3305
[5]Ohaegbulam KC,Liu W,Jeon H,et al.Tumor-expressed immune checkpoint B7x promotes cancer progression and antigen-specific CD8 T cell exhaustion and suppressive innate immune cells[J].Oncotarget,2017,8(47):82740-82753
[6]Knutson SK,Warholic NM,Wigle TJ,et al.Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2[J].PNAS,2013,110(19):7922-7927
[7]Wang Q,Hu B,Hu X,et al.Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment[J].Cancer cell,2018,33(1):152
[8]Hansen JD,Du Pasquier L,Lefranc MP,et al.The B7 family of immunoregulatory receptors:a comparative and evolutionary perspective[J].Molecular immunology,2009,46(3):457-472
[9]Huang BY,Zhan YP,Zong WJ,et al.The PD-1/B7-H1 pathway modulates the natural killer cells versus mouse glioma stem cells[J].PloSone,2015,10(8):e0134715
[10]Zhao H,Cheng Y,Dong S,et al.Down regulation of miR-143 promotes radiation-Induced thymic lymphoma by targeting B7H1[J]Toxicology letters,2017,280:116-124
[11]Zhi Y,Mou Z,Chen J,et al.B7H1 Expression and Epithelial-ToMesenchymal Transition Phenotypes on Colorectal Cancer Stem-Like Cells[J].PloS one,2015,10(8):e0135528
[12]Shen JK,Cote GM,Choy E,et al.Programmed cell death lig and 1expression inosteosarcoma[J].Cancerimmunology research,2014,2(7):690-698
[13]Cunha LL,Marcello MA,Morari EC,et al.Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation[J].Endocrine-related cancer,2013,20(1):103-110
[14]Du W,Zhu J,Chen Y,et al.Variant SNPs at the microRNA complementary site in the B7-H1 3'-untranslated region increase the risk of non-small cell lung cancer[J].Molecularmedicine reports,2017,16(3):2682-2690
[15]Berghoff AS,Ricken G,Widhalm G,et al.PD1(CD279)and PD-L1(CD274,B7H1)expression in primary central nervous system lymphomas(PCNSL)[J].Clinicalneuropathology,2014,33(1):42-49
[16]Wang F,Ma J,Liu J,et al.Synthetic small peptides acting on B7H1enhance apoptosis in pancreatic cancer cells[J].Molecular medicine reports,2012,6(3):553-557
[17]Kline J.Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer[J].Currentopinion in investigationa drugs(London,England:2000),2010,11(12):1354-1359
[18]Tsiaousidou A,Lambropoulou M,Chatzitheoklitos E,et al.B7H4HSP27 and DJ-1 molecular markers as prognostic factors in pancreatic cancer[J].Pancreatology:official journal of the International Association of Pancreatology(IAP),2013,13(6):564-569
[19]Yuan L,Dong L,Yu G,et al.Aberrant expression of B7-H4 may contribute to the development of hepatocellular carcinoma[J].Molecularmedicine reports,2016,14(6):5015-5024
[20]Liu L,Li D,Chen S,et al.B7-H4 expression in human infiltrating ductal carcinoma-associated macrophages[J].Molecularmedicine reports,2016,14(3):2135-2142
[21]Hong B,Qian Y,Zhang H,et al.Expression of B7-H4 and hepatitis Bvirus X in hepatitis B virus-related hepatocellular carcinoma[J].Worldjournal of gastroenterology,2016,22(18):4538-4546
[22]Choi H,Zhu G,Sica GL,et al.Genomic orgnaizationn and expression analysis of B7-H4,an immune inhibitory molecule of the B7family[J].J Immunol,2003,171(9):4650-4655
[23]Storniolo AM,Enas NH,Brown CA,et al.An investigational new drug treatment program for patients with gemcitabine:results for over3000 patients with pancreatic carcinoma[J].Cancer,1999,85:1261-1268
[24]Mugler,KC,Singh,M,Tringler,B,et al.B7-h4 expression in a range of breast pathology:correlation with tumor T-cell infiltration[J].Appl Immunohistochem Mol Morphol,2007,15:363-370
[25]Sun YP,Wang YS,Zhao JQ,et al.B7-H3 and B7-H4 expression in non-small-cell lung cancer[J].Lung Cancer,2006,53:143-151
[26]Krambeck AE,Thompson RH,Dong H,et al.B7-H4 expression in renal cell carcinoma and tumor vasculature:associations with cancer progression and survival[J].Proc Natl Acad Sci USA,2006,103:10391-10396
[27]Tsiaousidou A,Tsaroucha AK,Lambropoulou M,et al.Increased B7H4 tissue expression correlates with high CA199 serum levels and a worse prognosis of pancreatic adenocarcinoma[J].Clinicaland experimental medicine,2016,16(3):351-356
[28]Galazka K,Oplawski M,Windorbska W,et al.Theimmunohistochemical analysis of antigens such as RCAS1 and B7H4 in the cervical cancer nest and within the fibroblasts and macrophages infiltrating the cancer microenvironment[J].American journal of reproductive immunology(New York,N.Y.:1989),2012,68(1):85-93
[29]Sun Q,Li F,Li H,et al.Amniotic fluid stem cells provide considerable advantages in epidermal regeneration:B7H4 creates a moderate inflammation microenvironment to promote wound repair[J].Scientific reports,2015,5:11560