直肠癌患者HPV感染及APC、K-ras基因突变检测及其意义  

Detection of HPV infection and gene mutation of adenomatous polyposis coli and K-ras and its significance in patients suffering from rectal cancer

作　　者：王海江[1] 杨新辉[1] 范川文[1] 库热西[2] 赵泽亮[1] 赵为民[1] 孙振强[1] 

机构地区：[1]新疆医科大学附属肿瘤医院腹外科,乌鲁木齐830011 [2]新疆医科大学地方病分子生物学实验室,乌鲁木齐830054

出　　处：《肿瘤》2010年第8期682-686,共5页Tumor

基　　金：十一五国家科技支撑计划项目(编号:2006BAI02A06);新疆维吾尔自治区卫生厅青年科技人才专项基金(编号:2007Y38)

摘　　要：目的:通过检测直肠癌患者中人乳头状瘤病毒(human papilloma virus,HPV)感染,结肠腺瘤样息肉病(adenomatouspolyposis coli,APC)及K-ras基因突变的情况,探讨它们与直肠癌生物学行为之间的相关性,以及三者之间的相关性。方法:采用PCR法检测HPVDNA在直肠癌组织及正常结直肠黏膜组织中的表达;PCR-单链构象多态性(single-strand conformationpolymorphism,SSCP)银染法检测APC基因突变密集区(mutation cluster region,MCR)和K-ras基因第1外显子的突变情况。结果:75例直肠癌组织中检测到55例HPVDNA为阳性(73.3%),而在正常黏膜组织中未检测到HPVDNA的存在。HPV感染与患者年龄和淋巴结转移存在相关性,而与患者族别、肿瘤大小、肿瘤类型、组织学类型、Duke分期及浸润深度无关;APC基因突变43例(57.3%),K-ras基因突变34例(45.3%),均与患者年龄、组织学类型、侵袭深度、淋巴结转移及Duke分期无相关性;其中APC基因突变与患者性别存在相关性(P<0.05)。在有HPV感染的55例直肠癌中,同时伴有APC基因突变31例(56.4%),K-ras基因突变24例(43.6%);在HPV阴性的20例直肠癌中,APC基因突变12例(60.0%),K-ras基因突变10例(50.0%);在有APC基因突变的43例直肠癌组织中,同时伴有K-ras基因突变19例(44.2%),而无APC基因突变的32例直肠癌中,K-ras基因突变15例(46.9%),HPV感染、APC和K-ras基因突变三者间无相关性。结论:HPV感染可能是导致直肠癌恶性表型的重要因素;而APC和K-ras基因突变是直肠癌发生常见的早期分子事件。Objective：To detect human papilloma virus （HPV） infection and adenomatous polyposis coli （APC） and K-ras mutation and elucidate their relationship with biological behavior of rectal cancer and the correlation between each other. Methods：The expression of HPV DNA in rectal cancer tissues and normal colonrectal tissues was detected using PCR method. The mutations in the MCR of APC gene and the exon-1 of K-ras were detected by PCR-SSCP method. All results were analyzed combined with the clinical pathological data. Results：The positive expression of HPV DNA was detected in 55 out of 75 （73.3%） rectal cancer tissues but was not detected in normal mucosa tissues. HPV infection was related to the age of patients and lymph node metastasis, but not with the ethnic of pa- tients, tumor size, gross type, histological classification, Duke＇ s stage, and the depth of in,Jasion. APC gene mutation was detected in 43 （57.3%） cases and K-ras gene mutation was found in 34 （45.3%）. Both of them were not related with the age of patients, histological classification, the depth of invasion, lymph node metastasis, and Duke＇ s stage. APC gene mutation was related with the gender of patients （P 〈 0.05 ）. In 55 cases of HPV-infected rectal cancer tissues 31 （56.4%） specimens had APC mutation and 24 （43.6%） cases had K-ras mutation. In 20 HPV-negative rectal tissues 12 （60%） cases had APC mutation and 10 （50.0%） cases had K-ras mutation. In 43 cases with APC mutation, 19 （44.2%） cases showed K-ras mutation. In 32 tissues without APC mutation 15 （46.9%） cases showed K-ras mutation. There was no correlation among HPV infection, APC mutation, and K-ras mutation. Conclusion：Our findings suggest that HPV infection was an important factor in the development of the neoplastic phenotype of rectal cancer. APC and K-ras mutations were the early molecular events that frequently occurred in colon carcinogenesis.

关 键 词：直肠肿瘤 多肽现象 单链构象 乳头状瘤病毒 人 腺瘤性息肉病 结肠 K-RAS基因 

分 类 号：R735.37[医药卫生—肿瘤]