TROP2基因mRNA在左半结肠癌和右半结肠癌组织中的表达及其临床意义

Expression of TROP2 mRNA in left-sided and right-sided colon cancer and its clinical significance

目的探讨TROP2基因在左半结肠和右半结肠癌组织中的表达及其临床意义。方法选择2001年6月至2005年4月间在北京大学临床肿瘤学院接受根治性手术切除的Ⅱ、Ⅲ期结肠癌患者80例，其中右半结肠癌（RSCC）和左半结肠癌（LSCC）各40例。应用实时定量RT-PCR的方法检测TROP2 mRNA在癌组织和正常组织中的表达，并分析其与患者临床病理变量的关系及其对预后的影响。结果TROP2基因mRNA在左、右半结肠癌组织中的表达均显著高于自身正常结肠黏膜（P〈0.01）；然而，TROP2在LSCC中的表达明显高于RSCC（P=0.009）。LSCC中的TROP2高表达病例明显多于RSCC（67.5％：32.5％，P=0.002）；高表达组患者的癌相关病死率是低表达组的4倍（40％：10％，P=0.002）。Kaplan-Meier法分层分析显示，LSCC患者TROP2高表达者的中位生存时间明显短于低表达者（45.9个月：63.1个月，P=0.032）；而RSCC患者TROP2表达对生存时间没有影响（P=0.235）。多因素分析发现，肿瘤浸润深度和脉管癌栓是RSCC的独立预后因子；肿瘤浸润深度、淋巴结转移和脉管癌栓是LSCC的独立预后因子，TROP2高表达具有临界显著性（RR：6.244；95％CI：0.755.51.636；P=0.089）。结论TROP2与不良预后变量密切相关。TROP2基因在LSCC中的表达明显高于RSCC；TROP2高表达是LSCC患者潜在的独立预后因子；LSCC和RSCC可能是存在显著分子差异的两个不同的疾病。

Objective To investigate the expression of TROP2 in the left-sided and right-sided colon cancer and its clinical significance. Methods A total of eighty patients, who received radical resection of colon cancer between June 2001 and April 2005 and were staged as Ⅱ and Ⅲ, were identified, including forty with left-sided colon cancer（LSCC） and forty with right-sided colon cancer （RSCC）. The expression of TROP2 was detected by real-time quantitative RT-PCR in paired cancer and normal tissue. Subsequently, the relationship between TROP2 expession and clinicopathological variables as well as the effect on the patients＇ prognosis were analyzed. Results The expression of TROP2 mRNA in the cancer tissue was significantly higher than that in normal tissue （P〈0.01, paired Wilcoxon test）. However, its expression in LSCC was markedly higher than that in RSCC with significant difference （P=0.009, Mann-Whitney U test）. The patients with TROP2 high expression were found more frequently in LSCC than in RSCC （67.5% vs 32.5%, P=0.002, X^2 test）. Cancer-related mortality of the patients with TROP2 high expression was four times as high as low expression （40% vs 10%, P=0.002, X^2 test）. From the stratified survival analysis through Kaplan-Meier curve, the TROP2 high expression group had a significantly poorer median survival time than the low expression group for the patients with KSCC （45.9：63.1 months, P=0.032, log-rank test）. By contrast, for the patients with RSCC, TROP2 expression had no marked effect on the survival time （P=0.235, log-rank test）. In multivariable analysis, for the cohort of the present study, serosal invasion and lymphatic/vascular invasion were the independent prognostic factors of RSCC. Serosal invasion, lymph node metastasis and lymphatic/vascular invasion were the independent prognostic factors of LSCC. TROP2 high expression showed marginal significance （RR：6.244, 95% CI：0.755-51.636, P=0.089）. Conclusion （1）TROP2 is a differentially expressed gene between RSCC and I-SCC. （2）TROP2 high expression is closely related to the factors indicating poor prognosis. （3）TROP2 has distinct clinical significance to the patients with different tumor sites. TROP2 high expression is potentially an independent prognostic factor of LSCC. （4）LSCC and RSCC seem to be two distinct diseases with significant molecular heterogeneity.