| 江 宁,宗 丹,朱向帜.LASP1在鼻咽癌组织中的表达及其临床预后价值分析[J].中国肿瘤,2018,27(12):949-955. |
| LASP1在鼻咽癌组织中的表达及其临床预后价值分析 |
| Expression and Prognostic Value of LASP1 in Nasopharyngeal Carcinoma |
| 投稿时间：2018-09-29 |
| DOI：10.11735/j.issn.1004-0242.2018.12.A010 |
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| 中文关键词: 鼻咽肿瘤 LASP1 免疫组化 预后 总生存 |
| 英文关键词:nasopharyngeal neoplasms LASP1 immunohistochemistry prognosis overall survival |
| 基金项目:国家自然科学基金（81602381、81702693、81672989）； |
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| 中文摘要: |
| 摘 要：［目的］ 探讨LASP1在鼻咽癌组织中的表达与预后的关系，及其在鼻咽癌中的功能。［方法］ 免疫组化法检测79例鼻咽癌患者组织标本中LASP1蛋白的表达。Western Blot和Real-time PCR检测鼻咽癌细胞株中LASP1表达。Transwell小室实验明确体外LASP1对细胞迁移和侵袭能力的影响。Kaplan-Meier法分析LASP1表达与患者预后的关系，Cox比例风险回归模型分析LASP1表达在鼻咽癌患者预后预测中的价值。［结果］ LASP1在鼻咽癌组织（0.087±0.103）表达显著高于癌旁组织（0.016±0.010）（t=2.154，P=0.034）。LASP1在N2~3期（χ2=38.406，P<0.001）与Ⅳ期（χ2=4.595，P=0.043）患者表达较N0~1和Ⅱ~Ⅲ期患者更高。LASP1高表达与低表达两组患者总生存（overall survival，OS）、无远处转移生存（distant metastasis free survival，DMFS）和无局部复发生存（relapse free survival，RFS）分别为(114.5±8.5)个月 vs (137.5±4.6)个月(P=0.038）、(112.3±9.1)个月vs (140.3±3.8)个月（P=0.009）和(108.6±9.4)个月 vs (134.6±5.3)个月（P=0.029）。LASP1高表达（HR=4.437，95%CI：1.148~17.415，P=0.031）和TNM分期（HR=5.512，95%CI：1.075~28.254，P=0.041)是患者生存的独立预测因素。LASP1在鼻咽癌细胞株中表达（1.47±0.35）较正常鼻咽上皮细胞株（0.90±0.11）也显著升高（t=4.488，P<0.001）。过表达LASP1的鼻咽癌细胞株与对照组相比，Transwell小室细胞侵袭［（238.7±36.2） vs （48.7±11.6）］、迁移［（571.0±15.7） vs （91.6±20.3）］能力显著增强（P<0.01）。采用特异性shRNA敲低LASP1表达，鼻咽癌细胞体外侵袭［（168.7±14.6） vs （64.3±7.4）］和迁移［（205.0±9.8） vs （79.0±10.5）］能力受到抑制（P<0.01）。［结论］ LASP1在鼻咽癌组织和细胞中过表达，与鼻咽癌患者分期相关，且LASP1高表达是患者预后不良因素。体外功能实验表明LASP1发挥促进肿瘤侵袭和迁移功能。提示LASP1在鼻咽癌进展中发挥重要作用，可作为鼻咽癌诊治新的分子靶点。 |
| 英文摘要: |
| Abstract：［Purpose］ To explore the expression and prognostic value of LASP1 in nasopharyngeal carcinoma（NPC），and to identify the function of LASP1 in NPC. ［Methods］ Immunohistochemistry was adopted to determine LASP1 expression in 79 primary tumor samples and adjacent tissues from NPC patients. Western Blot and real time PCR were used to determine LASP1 expression in NPC cell lines. Transwell migration and invasion assay were used to determine the effect of LASP1 on cell migration and invasion in vitro. Kaplan-Meier plots were performed to investigate the prognostic relevance of LASP1 in univariate analysis. Multivariate analysis was performed by Cox proportional hazards models. ［Results］ LASP1 overexpressed in tumor tissues(0.087±0.103) compared with adjacent tissues(0.016±0.010)(t=2.154，P=0.034). The high expression of LASP1 was more frequent in patients with N2~3 (χ2=38.406，P<0.001) and stage Ⅳ(χ2=4.595，P=0.043) di-sease compared with N0~1 and stage Ⅱ~Ⅲ disease. The overall survival(OS)，distant metastasis free survival(DMFS) and relapse free survival(RFS) of patients with high and low expresson of LASP1 were(114.5±8.5) months vs (137.5±4.6) months(P=0.038)，(112.3±9.1) months vs (140.3±3.8) months(P=0.009)，and (108.6±9.4) months vs (134.6±5.3) months(P=0.029). High expression of LASP1(HR=4.437， 95%CI：1.148~17.415，P=0.031) and TNM staging(HR=5.512，95%CI： 1.075~28.254，P=0.041) were independent prognostic factor for OS in NPC patients. LASP1 was significantly up-regulated in NPC cell lines(1.47±0.35) in comparison with immortalized nasopharnx epithelial cells(0.90±0.11)(t=4.488，P<0.001). In comparison with control group，NPC cells with LASP1 over-expressed showed increased invasion(238.7±36.2 vs 48.7±11.6) and migration(571.0±15.7 vs 91.6±20.3)(P<0.01） potency. Moreover，LASP1 knockdown assay with specific sh-RNA significantly inhibited its invasion(168.7±14.6 vs 64.3±7.4) and migration(205.0±9.8 vs 79.0±10.5) in vitro(P<0.01). ［Conclusion］ LASP1 overexpression is observed in NPC cell lines and primary tumor of NPC patients，which is correlated with advanced disease and inferor survival. In vitro functional assays show that LASP1 promote tumor migration and invasion. It suggests that LASP1 plays crucial role in tumor progression and maybe serve as a therapeutic target in NPC. |
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