A novel molecular staging protocol for non-small cell lung cancer

被引:55
作者
Miyake, M [1 ]
Adachi, M
Huang, CL
Higashiyama, M
Kodama, K
Taki, T
机构
[1] Kitano Hosp, Tazuke Kofukai Med Res Inst, Dept Thorac Surg, Osaka 530, Japan
[2] Kitano Hosp, Tazuke Kofukai Med Res Inst, Dept Oncol 5, Osaka 530, Japan
[3] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Surg, Osaka 537, Japan
关键词
MRP-1/CD9; KA11/CD82; K-ras; p53; lung cancer; metastasis; prognosis; TM4SF;
D O I
10.1038/sj.onc.1202556
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A molecular staging protocol using reliable markers is of importance in predicting the prognosis of patients with non-small cell lung cancer (NSCLC) and for instituting their appropriate post-surgical treatment. We analysed tumor tissues from 187 NSCLC patients. The DNA and mRNA mere extracted from frozen specimens, and then polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to investigate mutations of p53 from exons 5-8, and mutations of K-ras at exon 1, To determine MRP-1/CD9 gene and KA11/CD82 gene expression, which have been postulated to be metastasis suppressor genes, we have applied quantitative RT-PCR, A Cox multivariate regression analysis showed that nodal status, MRP-1/CD9 and K-ras status were significant factors for prognosis (P<0.0001, P=0.0083 and P=0.0004, respectively). Based on these results, me classified the patients into three groups according to their MRP-1/CD9 and K-ras status. Patients with both MRP-1/CD9 positive and wild Ii-ras tumors were defined as group A, patients with either reduced MRP-1/CD9 or mutant Kr as tumors were defined as group B and patients with both reduced MRP-1/CD9 and mutant Ii-ras tumors were designated as group C, This new classification was significantly correlated with the tumor status and pathological stage (P=0.0098 and P=0.0017, respectively). The overall survival rate of the group A patients was significantly better than the group B patients (59.6% vs 27.9%, P=0.0001) and also that of group B patients mas better than the group C patients (27.9% vs 20.0%, P=0.0378), This tendency was also found in patients with 110 node-negative NSCLCs (A vs B vs C=75.8% vs 34.9%,fs 0.0%, P<0.0001), A Cox multivariate regression analysis in NSCLC patients demonstrated that an evaluation for both MRP-1/CD9 expression and K-ras mutations had a significant prognostic effect as well as nodal status (P<0.0001).
引用
收藏
页码:2397 / 2404
页数:8
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