Tensin1蛋白与胃癌临床病理特征及预后的关系

Associations between Tensin1 protein and clinicopathological characteristics and prognoses of gastric cancer patients

  • 摘要: 目的:探讨Tensin1蛋白表达水平与胃癌临床病理特征及预后的关系。
    方法:采用回顾性病例对照研究方法。收集2011年7月31日至2013年12月31日江苏大学附属医院收治的163例胃癌患者的临床病理资料。收集患者的术后胃癌组织和对应癌旁组织病理学标本,石蜡切片包埋,并行免疫组织化学染色检测。观察指标:(1)胃癌组织和癌旁组织中Tensin1蛋白表达情况。(2)胃癌组织中Tensin1蛋白表达与患者临床病理因素的关系。(3)随访和生存情况。(4)胃癌患者的预后因素分析。采用电话方式进行随访,了解患者生存情况。随访时间截至2017年1月1日。偏态分布的计量资料采用M(范围)表示。计数资料采用双侧x2或配对x2检验。采用KaplanMeier法绘制生存曲线计算生存率,Log-rank检验进行生存分析。单因素及多因素分析采用COX比例风险模型。
    结果:(1)胃癌组织和癌旁组织中Tensin1蛋白表达情况:免疫组织化学染色检测显示Tensin1蛋白在胃癌组织和癌旁组织细胞中主要表达于细胞质。163例患者,胃癌组织中154例Tensin1蛋白表达阳性(66例高表达、88例低表达),9例表达阴性;癌旁组织中79例Tensin1蛋白表达阳性(37例高表达、42例低表达),84例表达阴性;两者Tensin1蛋白表达阳性比例和表达水平比较,差异均有统计学意义(x2=64.65,12.93,P<0.05)。(2)胃癌组织中Tensin1蛋白表达与患者临床病理因素的关系:胃癌患者术后发生和未发生肿瘤转移患者胃癌组织中Tensin1蛋白高表达率分别为31.34%(21/67)和46.88%(45/96),两者比较,差异有统计学意义(x2=3.95,P<0.05)。(3)随访和生存情况:163例患者术后均获得随访,随访时间为3.3~64.7个月,中位随访时间为28.7个月。66例胃癌组织中Tensin1蛋白高表达患者3年累积无病生存率和累积总体生存率分别为63.12%和74.22%;97例胃癌组织中Tensin1蛋白低表达+阴性表达患者3年累积无病生存率和累积总体生存率分别为47.30%和55.74%;两者上述指标比较,差异均有统计学意义(x2=4.58,4.11,P<0.05)。亚组生存分析结果显示:肿瘤最大直径≥5 cm、神经和(或)脉管侵犯、TNM分期Ⅲ期的胃癌组织中Tensin1蛋白高表达患者的3年累积无病生存率分别为45.98%、62.79%、52.75%;Tensin1蛋白低表达+阴性表达患者分别为18.11%、31.10%、32.80%,上述生存情况比较,差异均有统计学意义(x2=5.85,7.89,4.96,P<0.05); Tensin1蛋白高表达患者3年累积总体生存率分别为66.00%、75.75%、67.93%,Tensin1蛋白低表达+阴性表达患者分别为30.74%、40.15%、44.67%,上述生存情况比较,差异均有统计学意义(x2=7.59,9.62,4.32,P<0.05)。(4)胃癌患者的预后因素分析,单因素分析结果显示:肿瘤最大直径、组织学分级、神经和(或)脉管侵犯、术后TNM分期、术后辅助化疗及Tensin1蛋白表达水平是影响胃癌患者预后的相关因素(风险比=3.66,2.45,2.17,3.36,0.41,0.54,95%可信区间:2.09~6.41,1.43~4.19,1.17~4.04,1.52~7.41,0.23~0.72,0.31~0.96, P<0.05)。多因素分析结果显示:肿瘤最大直径≥5 cm、组织学分级为Ⅲ级是影响胃癌患者预后的独立危险因素(风险比=3.21,2.17,95%可信区间:1.63~6.32,1.18~3.99,P<0.05);术后辅助化疗和Tensin1蛋白高表达是影响胃癌患者预后的独立保护因素(风险比=0.50,0.44,95%可信区间:0.28~0.90,0.24~0.82,P<0.05)。
    结论:Tensin1蛋白高表达可能抑制胃癌转移,是胃癌独立的保护性预后因素。

     

    Abstract: Objective:To investigate the associations between expression of Tensin1 protein and clinicpathological characteristics and prognoses of gastric cancer (GC) patients.
    Methods:The retrospective casecontrol study was conducted. The clinicopathological data of 163 GC patients who were admitted to the Affiliated Hospital of Jiangsu University between July 31, 2011 and December 31, 2013 were collected. The GC tissues and adjacent normal tissues were taken to paraffin imbedding, and then were detected by immunohistochemistry. Observation indicator: (1) expressions of Tensin1 protein in GC tissues and adjacent normal tissues; (2) association between expression of Tensin1 protein in GC tissues and clinicopathological characteristics; (3) followup and survival situations; (4) prognostic factors analysis. Followup using telephone interview was performed to detect survival up to January 1, 2017. Measurement data with skewed distribution were described as M (range). Count data were analyzed using the chisquare test or pairing chisquare test. The survival curve and rate were respectively drawn and calculated using the KaplanMeier method, and Log-rank test was used for survival analysis. The univariate analysis and multivariate analysis were done using the COX roportional hazard model.
    Results:(1) Expressions of Tensin1 protein in GC tissues and adjacent normal tissues: immunohistochemistry showed that Tensin1 protein in GC tissues and adjacent normal tissues mainly expressed in cytoplasm. Of 163 patients, 154 (66 with high expression and 88 with low expression) and 9 had respectively positive and negative expressions of Tensin1 protein in GC tissues; 79 (37 with high expression and 42 with low expression) and 84 had respectively positive and negative expressions of Tensin1 protein in adjacent normal tissues, with statistically significant differences in positive expression ratio and expression levels (x2=64.65, 12.93, P<0.05). (2) Association between expression of Tensin1 protein in GC tissues and clinicopathological characteristics: high expression rate of Tensin1 protein in GC tissues were respectively 31.34%(21/67) in GC patients with tumor metastases and 46.88%(45/96) in GC patients without tumor metastasis, with a statistically significant difference (x2=3.95, P<0.05). (3) Followup and survival situations: all the 163 patients were followed up for 3.3-64.7 months, with a median time of 28.7 months. The 3year cumulative diseasefree survival rate and cumulative overall survival rate in GC tissues were 63.12%, 74.22% in 66 patients with high expression of Tensin1 protein and 47.30%, 55.74% in 97 patients with low and negative expressions of Tensin1 protein, showing statistically significant differences in above indicators (x2=4.58, 4.11, P<0.05). Survival analysis of subgroups showed that 3year cumulative diseasefree survival rate in GC tissues of patients with maximum tumor dimension ≥ 5 cm, nerve and / or vascular invasions and stage Ⅲ of TNM staging were 45.98%, 62.79%, 52.75% in patients with high expression of Tensin1 protein and 18.11%, 31.10%, 32.80% in patients with low and negative expressions of Tensin1 protein, with a statistically significant difference (x2=5.85, 7.89, 4.96, P<0.05). The 3year cumulative overall survival rate was respectively 66.00%, 75.75%, 67.93% in patients with high expression of Tensin1 protein and 30.74%, 40.15%, 44.67% in patients with low and negative expressions of Tensin1 protein, with statistically significant differences (x2=7.59, 9.62, 4.32, P<0.05). (4) Prognostic factors analysis: results of univariate analysis showed that maximum tumor dimension, histological grade, nerve and / or vascular invasions, postoperative TNM staging, postoperative adjuvant chemotherapy and expression of Tensin1 protein were related factors affecting prognoses of GC patients [hazard ratio (HR)=3.66, 2.45, 2.17, 3.36, 0.41, 0.54, 95% confidence interval (CI): 2.09-6.41, 1.43-4.19, 1.17-4.04, 1.52-7.41, 0.23-0.72, 0.31-0.96, P<0.05]. Results of multivariate analysis showed that maximum tumor dimension ≥ 5 cm and grade Ⅲ of histological grade were independent risk factors affecting prognoses of GC patients (HR=3.21, 2.17, 95%CI: 1.63-6.32, 1.18-3.99, P<0.05), and postoperative adjuvant chemotherapy and high expression of Tensin1 protein were independent protective factors affecting prognoses of GC patients (HR=0.50, 0.44, 95%CI: 0.28-0.90, 0.24-0.82, P<0.05).
    Conclusion:High expression of Tensin1 protein may inhibit GC metastasis, and it is also an independent protective factor affecting prognoses of GC patients.

     

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