LMTK3、miR–449b–5p在膀胱癌中表达及与临床病理特征的关系

沈宁博; 但汉威

LMTK3、miR–449b–5p在膀胱癌中表达及与临床病理特征的关系

Expression of LMTK3 and miR-449b-5p in bladder cancer and their relationship with clinicopathological characteristics

摘要

摘要:
目的： 探讨狐猴酪氨酸激酶3（LMTK3）、miR–449b–5p在膀胱癌中表达及其与临床病理特征的关系。
方法： 选取97例膀胱癌病人作为研究对象，采用实时荧光定量PCR测定膀胱癌及其癌旁组织中LMTK3 mRNA、miR–449b–5p表达水平，采用免疫组织化学法检测LMTK3的表达，分析膀胱癌组织LMTK3、miR–449b–5p表达与病人临床病理特征的关系。使用TargetScan数据库分析LMTK3与miR–449b–5p是否存在结合位点。分析膀胱癌组织LMTK3与miR–449b–5p的相关性、LMTK3及miR–449b–5p表达与膀胱癌病人预后的关系、影响膀胱癌病人预后不良的危险因素。
结果： 与癌旁组比较，膀胱癌组织中LMTK3 mRNA水平、阳性表达率均明显升高（P ＜ 0.01），miR–449b–5p水平明显降低（P ＜ 0.01）。浸润深度≥5 cm、有神经浸润、组织学分级G3级、有淋巴结转移、有脉管浸润的膀胱癌组织中LMTK3阳性表达率均高于浸润深度＜5 cm、无神经浸润、组织学分级G1及G2级、无淋巴结转移、无脉管浸润的膀胱癌组织（P ＜ 0.05 ~ P ＜ 0.01）。根据膀胱癌组织中miR–449b–5p表达水平分为miR–449b–5p低表达组和miR–449b–5p高表达组，结果显示，浸润深度≥5 cm、有神经浸润、组织学分级G3级、有淋巴结转移、有脉管浸润的膀胱癌组织中miR–449b–5p表达水平均明显低于浸润深度＜5 cm、无神经浸润、组织学分级G1及G2级、无淋巴结转移、无脉管浸润的膀胱癌组织（P ＜ 0.01）。TargetScan数据库分析显示，LMTK3与miR–449b–5p存在结合位点。膀胱癌组织中miR–449b–5p表达水平与LMTK3表达呈明显负相关关系（r = –0.384，P ＜ 0.01）。Kaplan–Meier分析显示，LMTK3阳性表达者总生存率低于LMTK3阴性者（P ＜ 0.05），miR–449b–5p低表达者总生存率明显低于miR–449b–5p高表达者（P ＜ 0.01）；LMTK3阳性表达者无进展生存率低于阴性者（P ＜ 0.05），miR–449b–5p低表达者无进展生存率明显低于miR–449b–5p高表达者（P ＜ 0.01）。多因素COX分析表明，LMTK3阳性、miR–449b–5p低表达是影响膀胱癌病人预后不良的危险因素（P ＜ 0.05）。
结论： LMTK3、miR–449b–5p的表达与膀胱癌的发生发展有关，且与浸润深度、病理分级、TNM分期、淋巴结转移等密切相关。

Abstract:
Objective To investigate the expression of lemur tyrosine kinase 3 (LMTK3) and miR-449b-5p in bladder cancer and their relationship with clinicopathological characteristics.
Methods Ninety-seven patients with bladder cancer were selected as the study subjects. The expression levels of LMTK3 mRNA and miR-449b-5p in bladder cancer and its adjacent tissue were detected by real-time fluorescent quantitative PCR, the expression of LMTK3 was detected by immunohistochemistry, and the relationship between the expression of LMTK3 and miR-449b-5p in bladder cancer tissues and the clinicopathological characteristics of patients was analyzed. TargetScan database was used to analyze whether LMTK3 and miR-449b-5p having binding sites. The correlation between LMTK3 and miR-449b-5p in bladder cancer tissues, the relationship between the expression of LMTK3 and miR-449b-5p and the prognosis of bladder cancer patients, and the risk factors affecting the poor prognosis of bladder cancer patients were analyzed.
Results Compared with the adjacent tissue group, the level of LMTK3 mRNA and the positive expression rate in bladder cancer tissue were significantly increased (P ＜ 0.01), and the level of miR-449b-5p was significantly decreased (P ＜ 0.01). The positive expression rate of LMTK3 in bladder cancer tissue with invasion depth ≥ 5 cm, having nerve invasion, histological grade G3, having lymph node metastasis and vascular invasion was higher than that in bladder cancer tissue with invasion depth ＜ 5 cm, no nerve invasion, histological grade G1 and G2, no lymph node metastasis and vascular invasion (P ＜ 0.05 to P ＜ 0.01). According to the expression level of miR-449b-5p in bladder cancer tissues, the samples were divided into miR-449b-5p low expression group and miR-449b-5p high expression group, and the results showed that the expression level of miR-449b-5p in bladder cancer tissue with invasion depth ≥ 5 cm, having nerve invasion, histological grade G3, having lymph node metastasis and vascular invasion was significantly lower than that in bladder cancer tissue with invasion depth ＜ 5 cm, no nerve invasion, histological grade G1 and G2, no lymph node metastasis and vascular invasion (P ＜ 0.01). TargetScan database analysis showed that LMTK3 and miR-449b-5p had binding sites. The expression level of miR-449b-5p in bladder cancer tissue was significantly negatively correlated with the expression of LMTK3 (r = –0.384, P ＜ 0.01). Kaplan-Meier analysis showed that the total survival rate of patients with LMTK3 positive expression was lower than that of patients with LMTK3 negative expression (P ＜ 0.05), and the total survival rate of patients with miR-449b-5p low expression was significantly lower than that of patients with miR-449b-5p high expression (P ＜ 0.01); the progression-free survival rate of patients with LMTK3 positive expression was lower than that of patients with LMTK3negative expression (P ＜ 0.05), and the progression-free survival rate of patients with miR-449b-5p low expression was significantly lower than that of patients with miR-449b-5p high expression (P ＜ 0.01). Multivariate COX analysis showed that the positive expression of LMTK3 and low expression of miR-449b-5p were risk factors for poor prognosis in patients with bladder cancer (P ＜ 0.05).
Conclusions The expression of LMTK3 and miR-449b-5p is related to the occurrence and development of bladder cancer, and is closely correlated to the invasion depth, pathological grade, TNM staging, lymph node metastasis and so on.

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