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目的探索p53和kras作为肺癌早期基因诊断指标的可行性。方法选择北京协和医院呼吸内科41例有细胞学证据的原发性肺癌患者和15例临床诊断为肺结核或COPD的非肺癌患者痰标本,从中提取基因组DNA,以PCRSSCP银染法检测p53第5~8外显子突变。以北京协和医院病理科kras阳性肺癌细胞株提取的DNA作为阳性对照,以正常人血标本DNA作为阴性对照,用PCRSSP银染法检测kras第12位密码子的三种特异突变,即GGT→CGT/GTT/GAT。结果p53突变在肺癌组为22例,检出率为533%;非肺癌组为1例,检出率67%。在p53突变高龄肺癌患者(≥60岁)检出率高于低龄患者(<60岁),但与患者是否吸烟、性别、病理分型和疾病分期均无关。kras突变只在3例肺腺癌标本中检出,且均为GTT突变,灵敏度73%,特异度100%,说明单以kras作为肺癌的诊断指标不可取,灵敏度太低。实验中未发现p53和kras同时突变的病例。以p53作为肺癌诊断指标,其灵敏度为537%,特异度为933%、阳性似然比805、正确诊断指数047。联合p53和kras作为肺癌诊断或早期诊断的指标,则灵敏?
Objective To explore the feasibility of p53 and kras as early diagnostic markers of lung cancer. Methods A total of 41 primary lung cancer patients with cytological evidence and 15 non-lung cancer patients with clinically diagnosed pulmonary tuberculosis or COPD were selected from the Department of Respiratory Medicine, Peking Union Medical College Hospital. Genomic DNA was extracted from the lungs and PCR-SSCP-silver staining was used to detect p53. Exon 5-8 mutations. The DNA extracted from kras positive lung cancer cell line in pathology department of Peking Union Medical College Hospital was used as positive control, normal human blood sample DNA was used as negative control, and PCRSSPsilver staining was used to detect the three kinds of kras 12th codons. Specific mutations, namely GGT→CGT/GTT/GAT. Results There were 22 cases of p53 mutation in lung cancer group, the detection rate was 53. 3%, and 1 case in non-lung cancer group. The detection rate was 6.7%. The detection rate of older lung cancer patients (≥60 years old) with p53 mutation was higher than that of younger patients (<60 years old), but it was not related to whether the patient was smoking, gender, pathological type, and disease stage. The kras mutation was only detected in 3 lung adenocarcinoma specimens, and all were GTT mutations, with a sensitivity of 7.3% and a specificity of 100%, indicating that k-ras alone was not suitable for the diagnosis of lung cancer, and the sensitivity was too low. . No cases of simultaneous p53 and k-ras mutations were found in the experiment. Using p53 as a diagnostic marker for lung cancer, the sensitivity was 53.7%, the specificity was 93. 3%, the positive likelihood ratio was 805, and the correct diagnosis index was 047. Combined with p53 and k ras as indicators of lung cancer diagnosis or early diagnosis, then sensitive?