Expression of mucin-4 in bladder cancer and its mechanism
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摘要:
目的 探讨黏蛋白-4（mucin-4）在膀胱癌中的表达及作用机制。 方法 选取广东省两家三甲医院2016年1月~2017年6月期间收集的膀胱癌标本115例，同时选取距离肿瘤边缘>2 cm的癌旁组织作为对照。SYBR green实时荧光定量 PCR法和Western blot检测mucin-4在膀胱癌、癌旁组织中的相对表达量，并分析mucin-4与临床相关参数的关系，同时观察mucin-4过对T24细胞（膀胱癌细胞系）增殖、凋亡的影响。 结果 膀胱癌组织mucin-4的相对表达水平高于正常膀胱组织，差异具有统计学意义（P<0.05）。mucin-4的表达水平与膀胱癌的肿瘤大小、有无淋巴结转移以及TNM分期有关（P<0.05）；肿瘤直径大于5 cm组mucin-4的表达水平高于肿瘤直径小于5 cm组；有淋巴结转移的膀胱癌组mucin-4的表达水平高于无淋巴结转移的膀胱癌组；Ⅲ+Ⅳ期膀胱癌组mucin-4的表达水平明显高于Ⅰ+Ⅱ期膀胱癌，差异具有统计学意义（P<0.05）。mucin-4的表达水平与膀胱癌患者的年龄、性别无关（P>0.05）。上调mucin-4的表达，可以诱导膀胱癌细胞（T24细胞系）的增殖，抑制凋亡；下调mucin-4的表达，可以诱导膀胱癌细胞（T24细胞系）的凋亡，抑制增殖。 结论 mucin-4在膀胱癌的发生发展中起着重要作用，其表达水平对膀胱癌的严重程度及预后情况具有一定的参考价值。 Abstract:Objective To study the expression of mucin-4 in bladder cancer and its mechanism. Methods A total of 120 cases of bladder cancer admitted to our hospital from January 2015 to December 2016 were selected as experimental group and adjacent tissues 2cm around the tumor were selected as the control group. The relative expression of mucin-4 in bladder cancer and adjacent tissues was analyzed by SYBR green real-time quantitative PCR and western blot test. The relative expression of mucin-4 in bladder cancer carcinoma was analyzed and the relationship between mucin-4 and clinical features was analyzed. Results The relative expression level of mucin-4 in bladder cancer tissues was significantly higher than that in normal bladder tissues (P<0.05). The expression level of mucin-4 was associated with tumor size, lymph node metastasis, and TNM stage of bladder cancer (P<0.05). The expression level of mucin-4 in tumor tissues with diameter greater than 5 cm was higher than that in tumor group with diameter less than 5 cm. The expression level of mucin-4 in bladder transition group was higher than that in bladder transition group without lymph node metastasis. The expression level of mucin-4 in bladder tumor at III + IV stage was significantly higher than that at I + II stage (P<0.05). The expression level of mucin-4 was not related to the age and sex of bladder cancer patients (P>0.05). Mucin-4 overexpression induced the proliferation of bladder cancer cells (T24 cell line) and inhibited apoptosis, while mucin-4 knockout inhibited the proliferation of bladder cancer cells (T24 cell line) and induced apoptosis. It is suggested that mucin-4 can promote the proliferation of bladder cancer cells and inhibit apoptosis. Conclusion Mucin-4 plays an important role in the development and progression of bladder cancer, and its expression level has certain reference value for the severity and prognosis of bladder cancer. -
Key words:
- bladder cancer /
- mucin-4 /
- metastasis
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图 1 mucin-4在膀胱癌组织组织和癌旁组织的表达
*P<0.05 vs 正常组织; A: 目的基因QRT-PCR扩增产物电泳图像; B: mucin-4的相对表达量.
图 2 mucin-4过表达或者敲除时T24细胞增殖和凋亡情况（×40)
A, B: mucin-4过表达或者敲除时T24凋亡情况;C, D: mucin-4过表达或者敲除时T24增殖情况; P<0.05 vs 对照组
表 1 mucin-4的表达水平与膀胱癌临床相关参数的关系
变量 例数（%） mucin-4相对表达量 P 年龄（岁） <60 35（30.4%） 1.417 >0.05 ≥60 80（69.6%） 1.422 性别 男性 50（43.5%） 1.124 >0.05 女性 65（56.5%） 1.121 肿瘤大小（cm） ≥5 16（13.9%） 1.354 <0.05 <5 99（86.1%） 1.101 有无淋巴结转移 有 60（52.2%） 1.485 <0.05 无 55（47.8%） 1.131 TNM分期 Ⅰ+Ⅱ期 44（38.3%） 1.645 <0.05 Ⅲ+Ⅳ期 71（62.7%） 0.961 
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