STC2: A predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma

Yoshiaki Kita, Koshi Mimori, Masaaki Iwatsuki, Takehiko Yokobori, Keisuke Ieta, Fumiaki Tanaka, Hideshi Ishii, Hiroshi Okumura, Shoji Natsugoe, Masaki Mori

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)261-272
Number of pages12
JournalAnnals of Surgical Oncology
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

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Lymph Nodes
Neoplasm Metastasis
Esophageal Neoplasms
Microdissection
Neoplasms
Microarray Analysis
Genes
Lasers
teleocalcin
Esophageal Squamous Cell Carcinoma
Lymphatic Metastasis
Squamous Cell Neoplasms
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Survival Rate
Immunohistochemistry
Cell Line

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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STC2 : A predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma. / Kita, Yoshiaki; Mimori, Koshi; Iwatsuki, Masaaki; Yokobori, Takehiko; Ieta, Keisuke; Tanaka, Fumiaki; Ishii, Hideshi; Okumura, Hiroshi; Natsugoe, Shoji; Mori, Masaki.

In: Annals of Surgical Oncology, Vol. 18, No. 1, 01.01.2011, p. 261-272.

Research output: Contribution to journalArticle

Kita, Y, Mimori, K, Iwatsuki, M, Yokobori, T, Ieta, K, Tanaka, F, Ishii, H, Okumura, H, Natsugoe, S & Mori, M 2011, 'STC2: A predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma', Annals of Surgical Oncology, vol. 18, no. 1, pp. 261-272. https://doi.org/10.1245/s10434-010-1271-1
Kita, Yoshiaki ; Mimori, Koshi ; Iwatsuki, Masaaki ; Yokobori, Takehiko ; Ieta, Keisuke ; Tanaka, Fumiaki ; Ishii, Hideshi ; Okumura, Hiroshi ; Natsugoe, Shoji ; Mori, Masaki. / STC2 : A predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma. In: Annals of Surgical Oncology. 2011 ; Vol. 18, No. 1. pp. 261-272.
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AU - Yokobori, Takehiko

AU - Ieta, Keisuke

AU - Tanaka, Fumiaki

AU - Ishii, Hideshi

AU - Okumura, Hiroshi

AU - Natsugoe, Shoji

AU - Mori, Masaki

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N2 - 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.

AB - 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.

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