STC2: a predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma.
BACKGROUND
We sought to identify genes associated with the progression and metastasis of esophageal squamous-cell cancer by comparing the expression profiles of normal, primary cancer, and metastatic cancer cells isolated with laser microdissection.


METHODS
Oligo microarray analysis identified several lymph node-specific, metastasis-related genes. STC2 (stanniocalcin 2), which was overexpressed in esophageal cancer cases, was chosen for further characterization. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry were used to explore the clinicopathologic significance of STC2 expression status in 70 cases. Additionally, the functional role of STC2 in esophageal cancer was studied by the attenuation of STC2 in an esophageal cancer cell line.


RESULTS
Laser microdissection and oligo microarray analysis identified 63 candidate genes. Among them, STC2 showed higher expression in cancer tissue than in corresponding normal tissue (P < 0.001). STC2 expression was significantly correlated with lymph node metastasis, lymphatic invasion, and distant metastasis (P = 0.005, 0.007, and 0.038, respectively). Patients whose tumors had high STC2 expression had a worse 5-year survival rate than patients whose tumors had a low STC2 expression level (P = 0.016). STC2 transfected cells had a significantly higher proliferation rate than control cells (P < 0.001). Additionally, STC2 transfected cells were more invasive in vitro (P < 0.001) than control cells. These findings were validated by means of RNA interference assays.


CONCLUSIONS
We identified lymph node-specific, metastasis-related genes in esophageal cancer cells. One of these, STC2, may be associated with lymph node metastasis, making it a potential prognostic marker for esophageal cancer patients.
Kita
Yoshiaki
Y
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Mimori
Koshi
K
Iwatsuki
Masaaki
M
Yokobori
Takehiko
T
Ieta
Keisuke
K
Tanaka
Fumiaki
F
Ishii
Hideshi
H
Okumura
Hiroshi
H
Natsugoe
Shoji
S
Mori
Masaki
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; C114997:STC2 protein, human