Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings.
Peritoneal wash cytology plays a pivotal role in the decision for gastric cancer treatment because advanced gastric cancer often turns out incurable with peritoneal metastasis. Molecular detection of minimal cancer cells from peritoneal washings may overcome the sensitivity boundary of conventional cytology and contribute to the prediction of the disease outcome. To select marker candidates out of ten thousands of genes, we performed microarray analyses in 12 gastric cell lines and 8 peritoneal washings of early stage cases. With 40 candidates selected by the above expression profiling, RT-PCR in 16 representative peritoneal wash samples was performed to identify genes specific to cytology positive samples. The finally selected five genes, CK20, FABP1, MUC2, TFF1, and TFF2, were then evaluated for their utility as a marker for minimal residual disease in 99 peritoneal wash samples. Nested RT-PCR using the five genes showed positive results highly specific to incurable cases (91-100%). With a high specificity, the combination of these five genes succeeded in identifying 6 out of 20 (30%) additional patients with all types of early recurrence that could not be predicted by the conventional method. The six newly identified recurrences included four non-peritoneal ones, showing that RT-PCR using the five genes without a real-time quantitative PCR technique contributes to the detection of minimal residual disease.
Mori
Kazuhiko
K
Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Aoyagi
Kazuhiko
K
Ueda
Tetsuya
T
Danjoh
Inaho
I
Tsubosa
Yasuhiro
Y
Yanagihara
Kazuyoshi
K
Matsuno
Yoshihiro
Y
Sasako
Mitsuru
M
Sakamoto
Hiromi
H
Mafune
Ken ichi
Ki
Kaminishi
Michio
M
Yoshida
Teruhiko
T
Terada
Masaaki
M
Sasaki
Hiroki
H
D001202:Ascitic Fluid / Q000166:cytology; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D003581:Cytodiagnosis; D017931:DNA Primers / Q000235:genetics; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D053554:Keratin-20; D055262:Mucin-2; D009077:Mucins / Q000235:genetics; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D009479:Neuropeptides; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics; D010533:Peritoneal Lavage; D011506:Proteins; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D002352:Carrier Proteins; D017931:DNA Primers; C493319:FABP1 protein, human; C107608:FABP7 protein, human; C493320:Fabp1 protein, mouse; C493321:Fabp1 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005819:Genetic Markers; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; C489975:Krt20 protein, mouse; C524625:MUC2 protein, human; C524626:Muc2 protein, mouse; C524628:Muc2 protein, rat; D055262:Mucin-2; D009077:Mucins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D009479:Neuropeptides; D010455:Peptides; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C051838:TFF1 protein, human; C000604007:TFF2 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins