136例OSCC队列中肿瘤细胞的HIPK2表达情况及临床病理观察
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摘要
目的:确定同源结构域相互作用蛋白激酶-2(HIPK2)表达与口腔鳞状细胞癌(OSCC)的临床病理参数和预后的关系。方法:136例OSCC患者的石蜡包埋组织样品通过免疫组织化学方法检查HIPK2表达情况。评估HIPK2表达与OSCC临床病理特征和预后因素之间的关系。结果:OSCC中HIPK2的表达水平与淋巴结转移显著相关(P <0. 001)。HIPK2高水平表达的患者中位总生存时间(14,2～56个月)明显低于HIPK2低水平表达患者(43,4～93个月)(P <0. 001)和HIPK2中水平表达患者(38,2～81个月)(P <0. 001)。此外,HIPK2低表达组(39,2～93个月)(P <0. 001)和HIPK2中表达组(36,2～59个月)(P <0. 001)的中位无进展生存时间均比HIPK2高表达组(11,1～54个月)显著升高。以高HIPK2表达组为参考,低、中HIPK2表达组5年总生存期(OS)的相对危险度分别为0. 197(P <0. 001)和0. 271(P <0. 001),而低、中表达组的5年无复发生存期(RFS)的相对危险度分别为0. 371(P=0. 003)和0. 451(P=0. 014)。结论:HIPK2蛋白表达水平升高是OSCC结局的预测因素,并可能成为其潜在的治疗靶点。
Objective: To determine the association of homeodomain-interacting protein kinase-2(HIPK2) expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma(OSCC) patients. Methods: HIPK2 expression was examined using immunohistochemistry in paraffin-embedded tissue samples from 136 OSCC patients. Evaluate the association between HIPK2 expression and the clinicopathologic characteristics,prognostic factors in OSCC. Results: The expression of HIPK2 in OSCC was significantly associated with lymph node metastasis(P < 0. 001). The median overall survival of HIPK2 patients with high-level expression(14,2-56 months) was significantly lower than that of patients with low HIPK2 expression(43,4-93 months)(P < 0. 001) and medium HIPK2 levels(38,2-81 months)(P < 0. 001). In addition,the median progression-free survival time in HIPK2 low expression group(39,2-93 months)(P < 0. 001) and HIPK2 medium expression group(36,2-59 months)(P < 0. 001) was higher than that in the HIPK2 high expression group(11,1-54 months). Setting the high HIPK2 expression group as a reference,the relative risk of 5-year overall survival(OS) in the low and medium HIPK2 expression groups was 0. 197(P < 0. 001) and 0. 271(P < 0. 001),respectively. The relative risk of 5-year recurrence-free survival(RFS) in the low and middle expression groups was low,with degrees 0. 371(P = 0. 003) and0. 451(P = 0. 014),respectively. Conclusion: HIPK2 protein expression could be a predictive factor of outcome in OSCC and a promising therapeutic target.
Objective: To determine the association of homeodomain-interacting protein kinase-2(HIPK2) expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma(OSCC) patients. Methods: HIPK2 expression was examined using immunohistochemistry in paraffin-embedded tissue samples from 136 OSCC patients. Evaluate the association between HIPK2 expression and the clinicopathologic characteristics,prognostic factors in OSCC. Results: The expression of HIPK2 in OSCC was significantly associated with lymph node metastasis(P < 0. 001). The median overall survival of HIPK2 patients with high-level expression(14,2-56 months) was significantly lower than that of patients with low HIPK2 expression(43,4-93 months)(P < 0. 001) and medium HIPK2 levels(38,2-81 months)(P < 0. 001). In addition,the median progression-free survival time in HIPK2 low expression group(39,2-93 months)(P < 0. 001) and HIPK2 medium expression group(36,2-59 months)(P < 0. 001) was higher than that in the HIPK2 high expression group(11,1-54 months). Setting the high HIPK2 expression group as a reference,the relative risk of 5-year overall survival(OS) in the low and medium HIPK2 expression groups was 0. 197(P < 0. 001) and 0. 271(P < 0. 001),respectively. The relative risk of 5-year recurrence-free survival(RFS) in the low and middle expression groups was low,with degrees 0. 371(P = 0. 003) and0. 451(P = 0. 014),respectively. Conclusion: HIPK2 protein expression could be a predictive factor of outcome in OSCC and a promising therapeutic target.
引文
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[17]Kwon MJ,Kang SY,Nam ES,et al.HIPK2 overexpression and its prognostic role in human papillomavirus-positive tonsillar squamous cell carcinoma[J].Biomed Res Int,2017,2017(6):1056427.
[18]郑荟,魏光伟.HIPK2抑制非小细胞肺癌上皮间质转化及迁移侵袭的作用及机制[J].山东大学学报(医学版),2016,54(11):7-12.Zheng H,Wei GW.Mechanism function of HIPK2 in epithelialmesenchymal transition and migration of non-small cell lung cancer[J].J Shandong Univ(Health Sci),2016,54(11):7-12.
[2]Su SC,Lin CW,Liu YF,et al.Exome sequencing of oral squamous cell carcinoma reveals molecular subgroups and novel therapeutic opportunities[J].Theranostics,2017,7(5):1088-1099.
[3]Pan H,Gu L,Liu B,et al.Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma[J].PLoS One,2017,12(2):e0168900.
[4]Kuwano Y,Nishida K,Akaike Y,et al.Homeodomain-interacting protein kinase-2:a critical regulator of the DNA damage response and the epigenome[J].Int J of Mol Sci,2016,17(10):Pii:E1638.
[5]Feng Y,Zhou L,Sun X,et al.Homeodomain-interacting protein kinase 2(HIPK2):a promising target for anti-cancer therapies[J].Oncotarget,2017,8(12):20452-20461.
[6]Chang X,Zhen X,Liu J,et al.The antihelmenthic phosphate niclosamide impedes renal fibrosis by inhibiting homeodomain-interacting protein kinase 2 expression[J].Kidney Int,2017,92(3):612-624.
[7]Donninger H,Calvisi DF,Barnoud T,et al.NORE1A is a Ras senescence effector that controls the apoptotic/senescent balance of p53 via HIPK2[J].J Cell Biol,2015,208(6):777-789.
[8]Reuven N,Adler J,Porat Z,et al.The tyrosine kinase c-abl promotes homeodomain-interacting protein kinase 2(HIPK2)accumulation and activation in response to DNA damage[J].J Biol Chem,2015,290(27):16478-16488.
[9]Zhang Z,Wen P,Li F,et al.HIPK2 inhibits cell metastasis and improves chemosensitivity in esophageal squamous cell carcinoma[J].Exp Ther Med,2018,15(1):1113-1118.
[10]Kobir FML,Delnnocentes P,Agarwal P,et al.Estrogen receptor-α,progesterone receptor,and c-erbB/HER-family receptor mRNAdetection and phenotype analysis in spontaneous canine models of breast cancer[J].J Vet Sci,2017,18(2):149-158.
[11]李佳垚,吴洁,邱玲.下调HIPK2基因表达促进顺铂诱导的肾小管上皮细胞HKC凋亡[J].基础医学与临床,2017,37(7):1031-1036.Li JY,Wu J,Qiu L.Down-regulation of HIPK2 promotes cisplatin-induced apoptosis in human kidney tubular epithelial cells[J].Basic Clin Med,2017,37(7):1031-1036.
[12]Bokhari AA,Baker TM,Dorjbal B,et al.Nestin suppression attenuates invasive potential of endometrial cancer cells by downregulating TGF-βsignaling pathway[J].Oncotarget,2016,7(43):69733-69748.
[13]Conrad E,Polonio-Vallon T,Meister M,et al.HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylationcontrolled mechanism[J].Cell Death Differ,2016,23(1):110-122.
[14]Zhao YX,Zhang GY,Wang AY,et al.Role of Homeodomain-interacting protein kinase 2 in the pathogenesis of tissue fibrosis in keloid-derived keratinocytes[J].Ann Plast Surg,2017,79(6):546-551.
[15]Huang R,Zhang Y,Han B,et al.Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124-2HG[J].Autophagy,2017,13(10):1722-1741.
[16]Tan M,Gong H,Zeng Y,et al.Downregulation of homeodomaininteracting protein kinase-2 contributes to bladder cancer metastasis by regulating Wnt signaling[J].J Cell Biochem,2014,115(10):1762-1767.
[17]Kwon MJ,Kang SY,Nam ES,et al.HIPK2 overexpression and its prognostic role in human papillomavirus-positive tonsillar squamous cell carcinoma[J].Biomed Res Int,2017,2017(6):1056427.
[18]郑荟,魏光伟.HIPK2抑制非小细胞肺癌上皮间质转化及迁移侵袭的作用及机制[J].山东大学学报(医学版),2016,54(11):7-12.Zheng H,Wei GW.Mechanism function of HIPK2 in epithelialmesenchymal transition and migration of non-small cell lung cancer[J].J Shandong Univ(Health Sci),2016,54(11):7-12.