结直肠癌DNA依赖蛋白激酶催化亚单位、P16表达的临床病理意义

Clinicopathological significance of expressions of DNA dependent protein kinase catalytic subunit and P16 in colorectal carcinoma

目的研究结直肠癌DNA依赖蛋白激酶催化亚单位（DNA-PKcs）及P16表达的临床病理学特征并探讨与患者预后的关系。方法采用免疫组化PV6000二步法检测359例结直肠癌及35例癌旁正常组织DNA-PKcs及P16表达的状况并分析其与临床病理指标及预后的关系；提取16例新鲜结直肠癌手术标本的总蛋白并进行定量，通过Western印迹杂交法检测结直肠癌组织与癌旁正常组织中DNA-PKcs蛋白表达。结果免疫组化及Western印迹杂交法结果均显示，DNA-PKcs在结直肠癌组织中的表达显著高于在癌旁正常组织中的表达（均P〈0．05）；结直肠癌DNA-PKcs的阳性率为63．5％（228／359）。P16在结直肠癌组织中的表达显著高于癌旁正常组织（P〈0．05）；P16的阳性率为53．2％（191／359）。P16及DNA-PKcs的阳性表达均与患者的TNM分期、淋巴结转移情况以及腹腔和远处转移情况相关（均P〈0．05）。DNA-PKcs还与肿瘤的肠壁浸润深度及组织学分级呈正相关（均P〈0．05）。DNA-PKcs及P16阳性组患者的5年生存率均显著低于阴性组患者（均P〈0．05）。DNA-PKcs与P16在结直肠癌的表达呈正相关（r=0．149，P=0．036）。结论DNA-PKcs及P16在结直肠癌的发生和演化中可能发挥重要作用，并成为结直肠癌临床评价肿瘤生物学行为及判断预后的有用指标。

Objective To investigate the expression of DNA dependent protein kinase catalytic subunit （DNA-PKcs） and P16 （multiple tumor suppressor 1 ） genes in colorectal carcinoma and clinical significance thereof. Methods 359 specimens of colorectal carcinoma obtained during operation and 35 specimens of normal mucosa beside the carcinoma underwent immunohistochemical examination and Western blotting to detect the expression of DNA-PKcs and P16. Results The positive expression rates of DNA- PKcs and P16 of the colorectal carcinoma specimens were 63.5% （228/359） and 53.2% （191/359） respectively, both significantly higher than those of the para-cancer normal tissues （ both P 〈 0.05 ）. DNA- PKcs and P16 expression were both related to the clinical stage, lymphatic invasion, and distant metastasis （ all P 〈 0. 05 ）. The 5-year survival rates of the patients positive in DNA-PKcs and P16 expression were significantly lower than those of the patients negative in DNA-PKcs and P16 expression （ both P 〈 0.05 ）. The DNA-PKcs positive rate of the P16-positive patients was 78.6% , significantly higher than that of the P16-negativer patients （ 55. 3%, r = 0. 149, P = 0. 036 ）. Conclusion DNA-PKcs and P16 play a significant role in the carcinogenesis and evolution of colorectal carcinoma and may be used as one of the useful indicators for clinical assessment of tumor biological behavior and prognosis of colorectal carcinoma.