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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.

Background: Stanniocalcins are glycoprotein hormones that were originally found in the endocrine gland of bony fish. Microarray expression data from 32 paired samples of gastric cancer and normal mucosa in a public microarray database showed that the expression level of Stanniocalcin 2 was higher in gastric cancer than in normal gastric mucosa. The clinical significance of Stanniocalcin 2 expression has been observed for several cancers. However, the relationship between Stanniocalcin 2 and clinicopathological factors in gastric cancer has not yet been investigated., Materials and Methods: We examined the clinical significance of Stanniocalcin 2 in gastric cancer in 108 gastric cancer samples using real-time reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical studies were conducted with paraffin sections. The suppression analysis of Stanniocalcin 2 using siRNA was done to determine Stanniocalcin 2's biological roles., Results: The level of Stanniocalcin 2 in cancer tissues was higher than in normal tissues (P = .0002). The high Stanniocalcin 2 expression group (n = 54) had more progressive lymph node metastasis (P = .07) and venous invasion (P = .028) than the low-expression group (n = 54). High Stanniocalcin 2 expression was an independent prognostic factor in gastric cancer patients (P = .02). Moreover, siRNA suppression of Stanniocalcin 2 in a gastric cancer cell line inhibited cellular proliferation (P < .05)., Conclusions: The high expression level of Stanniocalcin 2 in gastric cancer tissues could be a very powerful marker of poor prognosis. Therefore, Stanniocalcin 2 is a promising candidate for a molecular target for the treatment of gastric cancer.

Laser microdissection (LMD) and microarray were used to identify genes associated with colorectal cancer. Stanniocalcin 2 (STC2) expression and clinicopathological significance in 139 clinical colorectal cancer samples were specifically investigated using real-time quantitative reverse transcription-polymerase chain reaction. A number of genes upregulated in colorectal cancer cells compared to normal colorectal epithelial cells were identified including STC2. STC2 gene expression in cancer tissue was higher than in corresponding normal colorectal epithelial tissue in 124 of 139 cases (89.2%, p < 0.01). Tumors with high STC2 expression showed higher frequencies of lymph node metastasis, lymphatic invasion, tumor depth, tumor size and AJCC Stage classification (p < 0.01). Patients with high STC2 expression also showed significantly worse overall survival rates than those with low STC2 expression (p < 0.01). Furthermore, STC2 gene appeared to be associated with colorectal cancer progression and may be a useful prognostic indicator for colorectal cancer.

Background: Human prominin-1 (PROM1, CD133) was used as a marker to detect stem cells (progenitor cells) and cancer stem cells (tumor-initiating cells) in various tissues. The purpose of this study was to investigate the biological and genetic characteristics of tumor-initiating cells in colon cancer with both in vitro and in vivo analyses., Methods: The CD133 expression of 12 colon cancer cell lines was evaluated. CD133+ cells were isolated by flow cytometry and examined for in vivo tumor formation, in vitro proliferation, colony formation, and invasion ability. Additionally, we used microarray analysis to compare gene expression profiles between CD133+ and CD133- isolated cells., Results: CD133+ cells were found in 5 of 12 colon cancer cell lines. Isolated CD133+ cells from the HT29 colon cancer cell line exhibited a higher tumorigenic potential than CD133- cells in the in vivo tumor formation assay. Furthermore, it was shown that CD133+ cells are more proliferative and have higher colony-forming and invasive abilities than CD133- cells in vitro. Microarray analysis found differential gene expression correlating with CD133 expression., Conclusions: It was confirmed that CD133+ cells in colon cancer are useful markers for the detection of tumor-initiating cells. Intimate biological and genetic features of CD133+ cells in colon cancer cell lines were also revealed. The biological characteristics of CD133+ cells and differentially expressed genes in these cells will help elucidate more details of tumor-initiating cells in colon cancer.