弥漫大B细胞淋巴瘤中HK-II、TNFAIP3异常表达与肿瘤细胞恶性特征的相关性
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摘要
目的:研究弥漫大B细胞淋巴瘤(DLBCL)中己糖激酶-Ⅱ(HK-Ⅱ)、肿瘤坏死因子α诱导蛋白3基因(TNFAIP3)异常表达与肿瘤细胞恶性特征的相关性。方法:选择2016年3月～2018年3月期间在我院手术切除的DLBCL患者作为DLBCL组,同期手术切除且经病理证实为淋巴结反应性增生的患者作为对照组,收集病灶后测定HK-Ⅱ、TNFAIP3、增殖基因、侵袭基因的表达量。结果:DLBCL组患者病灶内HK-Ⅱ的mRNA表达量明显高于对照组,TNFAIP3的mRNA表达量明显低于对照组;DLBCL组淋巴瘤分期Ⅲ～Ⅳ期、淋巴瘤分组B组患者病灶内HK-Ⅱ的mRNA表达量明显高于I～Ⅱ期患者、A组患者,TNFAIP3的mRNA表达量明显低于I～Ⅱ期患者、A组患者;DLBCL组患者病灶内CyclinD2、PDE4B、BCL2、XIAP、CCL5、CXCR4、MMP26的mRNA表达量明显高于对照组且与HK-II呈正相关、与TNFAIP3呈负相关,Caspase-3、TIMP4的mRNA表达量明显低于对照组且与HK-Ⅱ呈负相关、与TNFAIP3呈正相关。结论:DLBCL中HK-Ⅱ的高表达以及TNFAIP3的低表达与肿瘤病理进程、肿瘤细胞增殖及侵袭密切相关。
Objective:To study the correlation of the abnormal expression of hexokinase-Ⅱ(HK-Ⅱ)and tumor necrosis factor alpha-induced protein 3(TNFAIP3)and the malignant features of tumor cells in diffuse large B-cell lymphoma(DLBCL).Methods:DLBCL patients who underwent surgical resection in our hospital between March 2016 and March 2018 were selected as the DLBCL group,and the patients who underwent surgical resection and were pathologically confirmed as reactive hyperplasia of lymph nodes during the same period were selected as the control group.The lesions were collected to measure the expression levels of HK-Ⅱ,TNFAIP3,proliferation genes and invasion genes.Results:HK-Ⅱ mRNA expression level in the lesions of the DLBCL group was significantly higher than that of the control group while TNFAIP3 mRNA expression level was significantly lower than that of the control group;In DLBCL group,HK-Ⅱ mRNA expression levels in the lesions of patients with lymphoma stageⅢ-Ⅳ and lymphoma group B were significantly higher than those of the patients with lymphoma stage I-Ⅱand lymphoma group A while TNFAIP3 mRNA expression levels were significantly lower than those of the patients with lymphoma stage I-Ⅱ and lymphoma group A;In the lesions of the DLBCL group,CyclinD2,PDE4 B,BCL2,XIAP,CCL5,CXCR4 and MMP26 mRNA expression levels were significantly higher than those of the control group,and were positively correlated with HK-Ⅱ and negatively correlated with TNFAIP3;while Caspase-3 and TIMP4 mRNA expression levels were significantly lower than those of the control group,and were negatively correlated with HK-Ⅱ and positively correlated with TNFAIP3.Conclusions:The high expression of HK-Ⅱand the low expression of TNFAIP3 in DLBCL are closely related to the pathological process of tumor as well as the proliferation and invasion of tumor cells.
Objective:To study the correlation of the abnormal expression of hexokinase-Ⅱ(HK-Ⅱ)and tumor necrosis factor alpha-induced protein 3(TNFAIP3)and the malignant features of tumor cells in diffuse large B-cell lymphoma(DLBCL).Methods:DLBCL patients who underwent surgical resection in our hospital between March 2016 and March 2018 were selected as the DLBCL group,and the patients who underwent surgical resection and were pathologically confirmed as reactive hyperplasia of lymph nodes during the same period were selected as the control group.The lesions were collected to measure the expression levels of HK-Ⅱ,TNFAIP3,proliferation genes and invasion genes.Results:HK-Ⅱ mRNA expression level in the lesions of the DLBCL group was significantly higher than that of the control group while TNFAIP3 mRNA expression level was significantly lower than that of the control group;In DLBCL group,HK-Ⅱ mRNA expression levels in the lesions of patients with lymphoma stageⅢ-Ⅳ and lymphoma group B were significantly higher than those of the patients with lymphoma stage I-Ⅱand lymphoma group A while TNFAIP3 mRNA expression levels were significantly lower than those of the patients with lymphoma stage I-Ⅱ and lymphoma group A;In the lesions of the DLBCL group,CyclinD2,PDE4 B,BCL2,XIAP,CCL5,CXCR4 and MMP26 mRNA expression levels were significantly higher than those of the control group,and were positively correlated with HK-Ⅱ and negatively correlated with TNFAIP3;while Caspase-3 and TIMP4 mRNA expression levels were significantly lower than those of the control group,and were negatively correlated with HK-Ⅱ and positively correlated with TNFAIP3.Conclusions:The high expression of HK-Ⅱand the low expression of TNFAIP3 in DLBCL are closely related to the pathological process of tumor as well as the proliferation and invasion of tumor cells.
引文
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12 Suzuki O,Abe M,Hashimoto Y.Caspase-dependent drug-induced apoptosis is regulated by cell surface sialylation in human B-cell lymphoma[J].Oncol Lett,2015,10(2):687-690.
13章敬成,刘繁荣,胡慧仙,等.趋化因子CCL5与糖尿病相关的弥漫大B细胞淋巴瘤关系的实验研究[J].中国实验血液学杂志,2015,23(5):1325-1330.
14 Xu ZZ,Shen JK,Zhao SQ,et al.Clinical significance of chemokine receptor CXCR4and mammalian target of rapamycin(mTOR)expression in patients with diffuse large B-cell lymphoma[J].Leuk Lymphoma,2018,59(6):1451-1460.
15 AricòA,Giantin M,Gelain ME,et al.The role of vascular endothelial growth factor and matrix metalloproteinases in canine lymphoma:in vivo and in vitro study[J].BMC Vet Res,2013,3(9):94.
16冯永怀,吴柳松,苏俊,等.MMP-26、TIMP-4和MMP-9在弥漫大B细胞淋巴瘤中的表达及意义[J].中国实验血液学杂志,2013,21(5):1167-1172.
2 Shimono J,Miyoshi H,Kiyasu J,et al.Clinicopathological analysis of polyploid diffuse large B-cell lymphoma[J].PLoS One,2018,13(4):e0194525.
3许壁榆,邵霞,张义炜,等.shRNA干扰己糖激酶II基因表达对人淋巴瘤细胞恶性生物学行为的影响[J].肿瘤,2017,37:313-323,432.
4王玲玲,杨文秀,李逸,等.TNFAIP3siRNA对弥漫大B细胞淋巴瘤OCI-LY1细胞NF-κB活性及增殖的影响[J].临床与实验病理学杂志,2016,32(4):405-412.
5 Ollila TA,Olszewski AJ.Extranodal diffuse large B cell lymphoma:molecular features,prognosis,and risk of central nervous system recurrence[J].Curr Treat Options Oncol,2018,19(8):38.
6 Gao X,Li J,Wang Y,et al.Clinical characteristics and prognostic significance of EBER positivity in diffuse large B-cell lymphoma:A meta-analysis[J].PLoSOne,2018,13(6):e0199398.
7黄文涛,张惠箴,周晓燕,等.弥漫大B细胞淋巴瘤中CyclinD2的表达及其临床意义[J].临床与实验病理学杂志,2018,34(1):27-31.
8 Zlamalikova L,Moulis M,Salek D,et al.Expression of D-type cyclins in mantle cell and diffuse large B-cell lymphomas[J].Oncol Rep,2016,35(5):2673-2680.
9高倩,李艳艳,申亚男,等.PDE4B基因过表达对弥漫大B细胞淋巴瘤患者的预后价值[J].中华疾病控制杂志,2017,21(5):510-513.
10 Teoh CS,Lee SY,Chiang SK,et al.Impact of double expression of C-MYC/BCL2protein and cell of origin subtypes on the outcome among patients with diffuse large B-cell lymphoma:a single asian center experience[J].Asian Pac J Cancer Prev,2018,19(5):1229-1236.
11宋斌,陈雁,胡平,等.弥漫型大B细胞淋巴瘤患者XIAP与Survivin蛋白的表达及其相关性[J].现代肿瘤医学,2017,25(23):3831-3834.
12 Suzuki O,Abe M,Hashimoto Y.Caspase-dependent drug-induced apoptosis is regulated by cell surface sialylation in human B-cell lymphoma[J].Oncol Lett,2015,10(2):687-690.
13章敬成,刘繁荣,胡慧仙,等.趋化因子CCL5与糖尿病相关的弥漫大B细胞淋巴瘤关系的实验研究[J].中国实验血液学杂志,2015,23(5):1325-1330.
14 Xu ZZ,Shen JK,Zhao SQ,et al.Clinical significance of chemokine receptor CXCR4and mammalian target of rapamycin(mTOR)expression in patients with diffuse large B-cell lymphoma[J].Leuk Lymphoma,2018,59(6):1451-1460.
15 AricòA,Giantin M,Gelain ME,et al.The role of vascular endothelial growth factor and matrix metalloproteinases in canine lymphoma:in vivo and in vitro study[J].BMC Vet Res,2013,3(9):94.
16冯永怀,吴柳松,苏俊,等.MMP-26、TIMP-4和MMP-9在弥漫大B细胞淋巴瘤中的表达及意义[J].中国实验血液学杂志,2013,21(5):1167-1172.