A large-scale study of MT1-MMP as a marker for isolated tumor cells in peripheral blood and bone marrow in gastric cancer cases.
BACKGROUND
Recently, a marker for predicting metastasis or recurrence precisely in solid cancers has been focused on instead of the identification of isolated tumor cells detected by epithelial genes in circulating system. We identified a candidate marker in gastric cancer by microarray and validated it through a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay.


METHODS
To identify metastasis-related genes, we performed cDNA microarray analysis of total RNA from whole bone marrow blood from six cases with metastasis and three cases without metastasis. We determined clinical significance of the identified gene by microarray analysis with quantitative real-time RT-PCR in bone marrow and peripheral blood from 810 cases of gastric cancer.


RESULTS
We focused on membrane type 1 matrix metalloproteinase (MT1-MMP) as a candidate marker to predict distant metastasis among identified genes. MT1-MMP-positive expression in peripheral blood was associated with incidence of peritoneal dissemination, lymphatic permeation, vascular permeation, and lymph node metastasis. MT1-MMP-positive expression in bone marrow was also significantly related to the incidence of distant metastasis and peritoneal dissemination.


CONCLUSIONS
The expression of MT1-MMP in peripheral blood from gastric cancer cases was a powerful indicator of distant metastasis especially for peritoneal dissemination. The presence of MT1-MMP-expressing cells in bone marrow indicated higher risk for distant metastasis in gastric cancer cases.
Mimori
Koshi
K
Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, Japan.
Fukagawa
Takeo
T
Kosaka
Yoshimasa
Y
Ishikawa
Kenji
K
Iwatsuki
Masaaki
M
Yokobori
Takehiko
T
Hirasaki
Shigeo
S
Takatsuno
Yasushi
Y
Sakashita
Hiroyuki
H
Ishii
Hideshi
H
Sasako
Mitsuru
M
Mori
Masaki
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001853:Bone Marrow / Q000201:enzymology* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010534:Peritoneal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14