TMPRSS4在胃癌中的表达及其临床意义
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摘要
目的探讨TMPRSS4在胃癌中的表达及其临床意义。方法采用实时PCR方法检测30例相对正常胃黏膜和30例胃癌组织的TMPRSS4表达,同时采用免疫组织化学方法检测30例相对正常胃黏膜、18例胃腺瘤、122例原发胃癌及22例远处转移灶组织中TMPRSS4的表达,并结合临床病理因素进行相关性统计分析。结果实时PCR检测结果显示,TMPRSS4表达在胃癌组织中显著高于相对正常胃黏膜,差异有统计学意义(P=0.035)。免疫组织化学检测结果,TMPRSS4表达在原发胃癌及远处转移组织中显著高于非癌组织,随着临床分期的增长其表达呈逐渐升高趋势,差异有统计学意义(P <0.01)。TMPRSS4高表达与肿瘤大小、淋巴脉管浸润、肿瘤浸润深度、淋巴结转移、远处转移及TNM分期密切相关(P <0.05)。多变量Cox回归分析显示,TMPRSS4高表达是影响胃癌患者预后的独立因素(HR=2.72,P=0.005)。线性回归分析显示,原发肿瘤的TMPRSS4表达与远处转移灶的TMPRSS4表达呈正相关(β=0.307,R2=0.143,P=0.025)。结论 TMPRSS4高表达可作为评估胃癌进展的新型生物学指标,具有肿瘤生物学特性的TMPRSS4可能参与肿瘤转移的调控。
Objective To investigate the expression and clinical significance of TMPRSS4 expression in gastric cancer. Methods TMPRSS4 expression was evaluated in 30 normal mucosal and 30 gastric cancer tissue samples using real-time quantitative polymerase chain reaction(PCR) and in 30 cases of normal mucosa,18 cases of gastric dysplasia,122 cases of primary gastric cancer,and 22 cases of distant metastatic site using immunohistochemistry. The correlations between TMPRSS4 expression level and clinicopathologic factors were analyzed. Results Real-time quantitative PCR revealed that TMPRSS4 expression was significantly higher in gastric cancer tissues than that in normal mucosal tissues(P = 0.035). Immunohistochemistry showed significantly more TMPRSS4 expression in primary gastric cancer and distant metastasis tissues than that in noncancerous tissues,and a gradual increase was seen with increasing clinical staging(P < 0.01). TMPRSS4 overexpression was associated with tumor size,lymphovascular invasion,tumor invasion depth,lymph node metastasis,distant metastasis,and tumor,node,metastasis(TNM) stage(P < 0.05). Multivariate Cox regression analysis with the adjustment for TNM stage revealed that TMPRSS4 expression was an independent poor prognostic factor(HR = 2.72,P = 0.005). The index score of TMPRSS4 expression of the primary tumor showed a significant linear correlation with that of distant metastatic site(β = 0.307,R2 = 0.143,P = 0.025). Conclusion TMPRSS4 overexpression is a novel biomarker for estimating gastric cancer progression. The tumor biological context of TMPRSS4 may affect and participate in tumor metastasis.
Objective To investigate the expression and clinical significance of TMPRSS4 expression in gastric cancer. Methods TMPRSS4 expression was evaluated in 30 normal mucosal and 30 gastric cancer tissue samples using real-time quantitative polymerase chain reaction(PCR) and in 30 cases of normal mucosa,18 cases of gastric dysplasia,122 cases of primary gastric cancer,and 22 cases of distant metastatic site using immunohistochemistry. The correlations between TMPRSS4 expression level and clinicopathologic factors were analyzed. Results Real-time quantitative PCR revealed that TMPRSS4 expression was significantly higher in gastric cancer tissues than that in normal mucosal tissues(P = 0.035). Immunohistochemistry showed significantly more TMPRSS4 expression in primary gastric cancer and distant metastasis tissues than that in noncancerous tissues,and a gradual increase was seen with increasing clinical staging(P < 0.01). TMPRSS4 overexpression was associated with tumor size,lymphovascular invasion,tumor invasion depth,lymph node metastasis,distant metastasis,and tumor,node,metastasis(TNM) stage(P < 0.05). Multivariate Cox regression analysis with the adjustment for TNM stage revealed that TMPRSS4 expression was an independent poor prognostic factor(HR = 2.72,P = 0.005). The index score of TMPRSS4 expression of the primary tumor showed a significant linear correlation with that of distant metastatic site(β = 0.307,R2 = 0.143,P = 0.025). Conclusion TMPRSS4 overexpression is a novel biomarker for estimating gastric cancer progression. The tumor biological context of TMPRSS4 may affect and participate in tumor metastasis.
引文
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[5] LEE Y,KO D,MIN HJ,et al. TMPRSS4 induces invasion and proliferation of prostate cancer cells through induction of Slug and cyclin D1[J]. Oncotarget,2016,7(31):50315-50332. DOI:10.18632/oncotarget.10382.
[6] LI XM,LIU WL,CHEN X,et al. Overexpression of TMPRSS4 promotes tumor proliferation and aggressiveness in breast cancer[J]. Int J Mol Med,2017,39(4):927-935. DOI:10.3892/ijmm.2017.2893.
[7] KIM S,KANG HY,NAM EH,et al. TMPRSS4 induces invasion and epithelial-mesenchymal transition through upregulation of integrin alpha5 and its signaling pathways[J]. Carcinogenesis,2010,31(4):597-606. DOI:10.1093/carcin/bgq024.
[8] NAM EH,LEE Y,ZHAO XF,et al. ZEB2-Sp1 cooperation induces invasion by upregulating cadherin-11 and integrinα5 expression[J].Carcinogenesis,2014,35(2):302-314. DOI:10.1093/carcin/bgt340.
[9] MIN HJ,LEE Y,ZHAO XF,et al. TMPRSS4 upregulates uPA gene expression through JNK signaling activation to induce cancer cell invasion[J]. Cell Signal,2014,26(2):398-408. DOI:10.1016/j.cellsig.2013.08.002.
[10] LUO ZY,WANG YY,ZHAO ZS,et al. The expression of TMPRSS4and Erk1 correlates with metastasis and poor prognosis in Chinese patients with gastric cancer[J]. PLoS One,2013,8(7):e70311.DOI:10.1371/journal.pone. 0070311.
[11]王焕景,智发朝,赵芯梅,等. TMPRSS4基因沉默对胰腺癌SW1990细胞生长及侵袭的影响[J].中华胰腺病杂志,2011,11(3):187-189. DOI:10.3760/cma.j.issn.1674-1935.2011.03.012.
[2] JUNG H,LEE KP,PARK SJ,et al. TMPRSS4 promotes invasion,migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition[J]. Oncogene,2008,27(18):2635-2647. DOI:10.1038/sj.onc.1210914.
[3] YUAN H,CHEN Z,BAI S,et al. Molecular mechanisms of lncRNA SMARCC2/miR-551b-3p/TMPRSS4 axis in gastric cancer[J]. Cancer Lett,2018,418:84-96. DOI:10.1016/j.canlet.2018.01.032.
[4] KIM S,LEE JW. Membrane proteins involved in epithelial-mesenchymal transition and tumor invasion:studies on TMPRSS4 and TM4SF5[J]. Genomics Inform,2014,12(1):12-20. DOI:10.5808/GI.2014.12.1.12.
[5] LEE Y,KO D,MIN HJ,et al. TMPRSS4 induces invasion and proliferation of prostate cancer cells through induction of Slug and cyclin D1[J]. Oncotarget,2016,7(31):50315-50332. DOI:10.18632/oncotarget.10382.
[6] LI XM,LIU WL,CHEN X,et al. Overexpression of TMPRSS4 promotes tumor proliferation and aggressiveness in breast cancer[J]. Int J Mol Med,2017,39(4):927-935. DOI:10.3892/ijmm.2017.2893.
[7] KIM S,KANG HY,NAM EH,et al. TMPRSS4 induces invasion and epithelial-mesenchymal transition through upregulation of integrin alpha5 and its signaling pathways[J]. Carcinogenesis,2010,31(4):597-606. DOI:10.1093/carcin/bgq024.
[8] NAM EH,LEE Y,ZHAO XF,et al. ZEB2-Sp1 cooperation induces invasion by upregulating cadherin-11 and integrinα5 expression[J].Carcinogenesis,2014,35(2):302-314. DOI:10.1093/carcin/bgt340.
[9] MIN HJ,LEE Y,ZHAO XF,et al. TMPRSS4 upregulates uPA gene expression through JNK signaling activation to induce cancer cell invasion[J]. Cell Signal,2014,26(2):398-408. DOI:10.1016/j.cellsig.2013.08.002.
[10] LUO ZY,WANG YY,ZHAO ZS,et al. The expression of TMPRSS4and Erk1 correlates with metastasis and poor prognosis in Chinese patients with gastric cancer[J]. PLoS One,2013,8(7):e70311.DOI:10.1371/journal.pone. 0070311.
[11]王焕景,智发朝,赵芯梅,等. TMPRSS4基因沉默对胰腺癌SW1990细胞生长及侵袭的影响[J].中华胰腺病杂志,2011,11(3):187-189. DOI:10.3760/cma.j.issn.1674-1935.2011.03.012.