Expression of gemcitabine- and cisplatin-related genes in non-small-cell lung cancer.
The aim of this study was to investigate the influence of histology and site of analysis (primary tumor versus lymph node) on the expression of genes involved in gemcitabine and cisplatin activity in non-small-cell lung cancer (NSCLC). Excision repair cross-complementing-1 (ERCC1), human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), 5'-nucleotidase (5'-NT), cytidine deaminase (CDA) and ribonucleotide-reductase regulatory subunits (RRM1 and RRM2) were analyzed by quantitative-reverse transcription-PCR in 88 microdissected samples from 69 chemonaive patients. The results showed different patterns of expression for all studied genes, suggesting a possible stratification of the patients. No difference was observed between primary tumor and lymph node metastasis, as well as in adenocarcinoma and squamous-cell carcinoma specimens, while we found a correlation between the CDA-A79C polymorphism and gene expression levels. These data suggest a similar genetic susceptibility to gemcitabine-cisplatin regimens for squamous cell and adenocarcinoma and support the use of both lymph node and primary tumor for the expression profiling of NSCLC.
Toffalorio
F
F
Clinical Pharmacology and New Drug Development Unit, European Institute of Oncology, Milan, Italy. francesca.toffalorio@ieo.it
Giovannetti
E
E
De Pas
T
T
Radice
D
D
Pelosi
G
G
Manzotti
M
M
Minocci
D
D
Spaggiari
L
L
Spitaleri
G
G
Noberasco
C
C
Catania
C
C
Boselli
S
S
Danesi
R
R
de Braud
F
F
D015720:5'-Nucleotidase / Q000235:genetics; D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism; D003842:Deoxycytidine Kinase / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D034741:RNA, Small Interfering / Q000494:pharmacology; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000093542:Gemcitabine
D004268:DNA-Binding Proteins; D033721:Equilibrative Nucleoside Transporter 1; D034741:RNA, Small Interfering; C438649:SLC29A1 protein, human; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C093713:ribonucleotide reductase M2; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D003842:Deoxycytidine Kinase; C071447:ERCC1 protein, human; D004720:Endonucleases; D015720:5'-Nucleotidase; D003564:Cytidine Deaminase; D002945:Cisplatin; D000093542:Gemcitabine