血清K-ras基因突变检测联合CA19-9测定在胰腺癌诊断中的应用

Significance of Detection of K-ras Gene Mutations and CA19-9 in Serum for Diagnosis of Pancreatic Carcinoma

背景与目的:胰腺癌早期诊断困难,常用的肿瘤标记物如CA19-9,虽敏感度较高但特异性较差,胰腺癌中常有K-ras基因的突变,而且特异性较高,我们通过检测血清DNA中K-ras基因的突变以及测定血清CA19-9的含量,以探讨两者联合检测在胰腺癌诊断中的临床意义。方法:取39例胰腺癌患者的血清,抽提DNA,采用突变富集聚合酶链反应-限制性片段长度多态性法检测K-ras基因第12密码子突变,同时应用放免法测定血清CA19-9的含量,并与17例其他胰腺疾病患者和21例健康者的血清检测结果作对照,分析两者联合应用的临床诊断价值。结果:在28例胰腺癌和2例其它胰腺疾病患者血清中检测到K-ras基因突变,阳性率分别为71.79%和11.76%;而血清CA19-9测定的阳性率则分别为71.79%和41.18%。平行法联合检测K-ras和CA19-9诊断胰腺癌时敏感性增至94.87%,系列法联合检测时特异性增至94.12%。21例健康对照者血清中K-ras基因与CA19-9均无异常。结论:联合血清K-ras基因突变检测与CA19-9测定可提高胰腺癌诊断的特异性和敏感性,具有一定的临床应用价值。

BACKGROUND &OBJECTIVE: The early diagnosis of pancreatic carcinoma is difficult. The serum tumor markers such as CA19 9 have a relatively high sensitivity but with low specificity. The oncogene K ras is frequently mutated in pancreatic carcinoma and with high specificity. The aim of this study was to assess the feasibility of detection of K ras mutation combined with serum content of CA19 9 as an approach for diagnosis of pancreatic carcinoma. METHODS: Serum DNA was extracted from 39 patients with pancreatic carcinoma. Mutation enriched polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) was used to determine codon 12 mutations of K ras. Serum content of CA19 9 was determined by radioimmunoassay. In addition, the sera from 17 patients with other pancreatic diseases and 21 healthy individuals were also analyzed as control. RESULTS: K ras gene mutations at codon 12 were detected in the sera of 71.79%(28/39) patients with pancreatic carcinoma and 11.76%(2/17) of patients with benign pancreatic tumors. The positive rates of CA19 9 were 71.79%and 41.18%, respectively. Parallel combined test increased the diagnostic sensitivity to 94.87%; and serial combined test increased the diagnostic specificity to 94.12%. Negative results of K ras gene and CA19 9 were obtained in all sera from healthy controls. CONCLUSION: Combined detection of K ras mutation and CA19 9 could increase the sensitivity and specificity in diagnosing pancreatic carcinoma, and would seem to be merited in clinic.