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
相关论文
共 32 条
[21]   CORRELATION OF EXPRESSION OF H/LE(Y)/LE(B) ANTIGENS WITH SURVIVAL IN PATIENTS WITH CARCINOMA OF THE LUNG [J].
MIYAKE, M ;
TAKI, T ;
HITOMI, S ;
HAKOMORI, S .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (01) :14-18
[22]  
Miyake M, 1996, CANCER RES, V56, P1244
[23]   Revisions in the International System for Staging Lung Cancer [J].
Mountain, CF .
CHEST, 1997, 111 (06) :1710-1717
[24]   MOLECULAR-STRUCTURE OF THE HUMAN CYTOPLASMIC BETA-ACTIN GENE - INTERSPECIES HOMOLOGY OF SEQUENCES IN THE INTRONS [J].
NAKAJIMAIIJIMA, S ;
HAMADA, H ;
REDDY, P ;
KAKUNAGA, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (18) :6133-6137
[25]  
ROSELL R, 1993, ONCOGENE, V8, P2407
[26]   Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer [J].
Roth, JA ;
Nguyen, D ;
Lawrence, DD ;
Kemp, BL ;
Carrasco, CH ;
Ferson, DZ ;
Hong, WK ;
Komaki, R ;
Lee, JJ ;
Nesbitt, JC ;
Pisters, KMW ;
Putnam, JB ;
Schea, R ;
Shin, DM ;
Walsh, GL ;
Dolormente, MM ;
Han, CI ;
Martin, FD ;
Yen, N ;
Xu, K ;
Stephens, LC ;
McDonnell, TJ ;
Mukhopadhyay, T ;
Cai, D .
NATURE MEDICINE, 1996, 2 (09) :985-991
[27]  
SAMBROOK J, 1989, LAB MANUAL, V3, pE3
[28]   THE RAS ONCOGENES INCREASE THE INTRINSIC RESISTANCE OF NIH-3T3 CELLS TO IONIZING-RADIATION [J].
SKLAR, MD .
SCIENCE, 1988, 239 (4840) :645-647
[29]   K-RAS ONCOGENE ACTIVATION AS A PROGNOSTIC MARKER IN ADENOCARCINOMA OF THE LUNG [J].
SLEBOS, RJC ;
KIBBELAAR, RE ;
DALESIO, O ;
KOOISTRA, A ;
STAM, J ;
MEIJER, CJLM ;
WAGENAAR, SS ;
VANDERSCHUEREN, RGJRA ;
VANZANDWIJK, N ;
MOOI, WJ ;
BOS, JL ;
RODENHUIS, S .
NEW ENGLAND JOURNAL OF MEDICINE, 1990, 323 (09) :561-565
[30]   SOMATIC GENETIC CHANGES IN LUNG-CANCER AND PRECANCEROUS LESIONS [J].
SUNDARESAN, V ;
HEPPELLPARTON, A ;
COLEMAN, N ;
MIOZZO, M ;
SOZZI, G ;
BALL, R ;
CARY, N ;
HASLETON, P ;
FOWLER, W ;
RABBITTS, P .
ANNALS OF ONCOLOGY, 1995, 6 :27-32