Yuan Hang, Tu Shi-Liang, He Xu-Jun
Department of Colon and Rectal Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
Zhonghua Wai Ke Za Zhi. 2013 Jun 1;51(6):547-51.
To study p53 up-regulated modulator of apoptosis (PUMA) and bcl-2 interacting mediator of cell death (BIM) of the BH3-only protein family expression in colorectal cancer tissues and its relationship with colorectal cancer invasion, metastasis and prognosis.
Immunohistochemical staining (EnVision) was used to detect PUMA/BIM expression in 30 cases of normal mucosa, 30 cases of colorectal adenoma and 142 cases of colorectal cancer tissues.
PUMA in colorectal cancer tissues was positive expressed (82.4%), which was significantly lower than in the normal mucosa colorectal adenomas (96.7%) and normal mucosa tissues (96.7%) (both χ(2) = 3.93, P < 0.05). Positive expression rate of BIM in colorectal cancer tissues (62.7%) was significantly lower than that in colorectal adenomas and normal mucosa (96.7% and 90.0%) (χ(2) = 8.42 and 13.29, P < 0.01). PUMA and BIM in colorectal cancer tissues were positively correlated (r = 0.747, P = 0.000). PUMA expression was related to tumor differentiation (χ(2) = 11.87), invasion depth (χ(2) = 11.59), lymph node metastasis (χ(2) = 12.82), TNM stage (χ(2) = 33.47) and P-gp expression (χ(2) = 18.30), all P < 0.05, but not related to the patients' age, gender, tumor size, tumor histological type and GST-π expression (P > 0.05). BIM expression was related to tumor differentiation (χ(2) = 16.19), lymph node metastasis (χ(2) = 14.95), TNM stage (χ(2) = 52.66) and P-gp expression (χ(2) = 10.60) (P < 0.05), but not related to patients' age, sex, tumor size, tumor histological type, invasion depth and GST-π expression (P > 0.05). 1-, 3-, 5-year survival rates of the positive expression of PUMA/BIM in patients with colorectal cancer were significantly higher than that of PUMA/BIM in patients with negative expression (χ(2) = 6.10 and 27.6, P < 0.05). Cox multivariate analysis showed that lymph node metastasis (RR = 0.238), TNM stage (RR = 7.895), PUMA (RR = 1.691) and BIM (RR = 0.440) could be used as independent prognostic indicators (P < 0.05).
PUMA and BIM expressions in colorectal cancer are related to the tumor invasion, metastasis and prognosis. Low expressions of PUMA and BIM were related to the late period and poor prognosis of colorectal cancer patients.
研究仅含BH3结构域蛋白家族中凋亡p53上调调节因子(PUMA)和细胞死亡bcl-2相互作用介质(BIM)在结直肠癌组织中的表达及其与结直肠癌侵袭、转移和预后的关系。
采用免疫组织化学染色(EnVision法)检测30例正常黏膜、30例结直肠腺瘤和142例结直肠癌组织中PUMA/BIM的表达。
结直肠癌组织中PUMA阳性表达率为82.4%,明显低于正常黏膜(96.7%)和结直肠腺瘤(96.7%)(χ² = 3.93,P < 0.05)。结直肠癌组织中BIM阳性表达率(62.7%)明显低于结直肠腺瘤和正常黏膜(分别为96.7%和90.0%)(χ² = 8.42和13.29,P < 0.01)。结直肠癌组织中PUMA与BIM呈正相关(r = 0.747,P = 0.000)。PUMA表达与肿瘤分化(χ² = 11.87)、浸润深度(χ² = 11.59)、淋巴结转移(χ² = 12.82)、TNM分期(χ² = 33.47)及P-糖蛋白表达(χ² = 18.30)均有关,P均 < 0.05,但与患者年龄、性别、肿瘤大小、肿瘤组织学类型及谷胱甘肽S-转移酶-π(GST-π)表达无关(P > 0.05)。BIM表达与肿瘤分化(χ² = 16.19)、淋巴结转移(χ² = 14.95)、TNM分期(χ² = 52.66)及P-糖蛋白表达(χ² = 10.60)有关(P < 0.05),但与患者年龄、性别、肿瘤大小、肿瘤组织学类型、浸润深度及GST-π表达无关(P > 0.05)。结直肠癌患者中PUMA/BIM阳性表达者1年、3年、5年生存率明显高于PUMA/BIM阴性表达者(χ² = 6.10和27.6,P < 0.05)。Cox多因素分析显示,淋巴结转移(RR = 0.238)、TNM分期(RR = 7.895)、PUMA(RR = 1.691)和BIM(RR = 0.440)可作为独立的预后指标(P < 0.05)。
结直肠癌中PUMA和BIM表达与肿瘤侵袭、转移及预后有关。PUMA和BIM低表达与结直肠癌患者晚期及预后不良有关。