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STC2: A Predictive Marker for Lymph Node Metastasis in Esophageal Squamous-Cell Carcinoma

  • Translational Research and Biomarkers
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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.

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Acknowledgment

Supported by CREST, Japan Science and Technology Agency; and the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (Grants 21679006, 20390360, 20590313, 20591547, 21591644, 21592014, 20790960, and 21791297). We express our appreciation to T. Shimooka, K. Ogata, M. Oda, M. Kasagi, Y. Nakagewa, S. Matsuzaki, M. Kawamoto, Y. Fukuyoshi, A. Harada, Dr. N. Haraguchi, Dr. M. Ohkuma, Dr. K. Sakashita, Dr. Y. Takatsuno, Dr. K. Motoyama, Dr. T. Yokoe, Dr. Z. Xiang, Dr. Y. Kosaka, Dr. S. Hirasaki, Dr. K. Ishikawa, Dr. Y. Nakamura, and Dr. H. Sakashita for their technical assistance and advice.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan

    Yoshiaki Kita MD, PhD, Koshi Mimori MD, PhD, Masaaki Iwatsuki MD, PhD, Takehiko Yokobori MD, PhD, Keisuke Ieta MD, PhD, Fumiaki Tanaka MD, PhD & Hideshi Ishii MD, PhD

  2. Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan

    Yoshiaki Kita MD, PhD, Hiroshi Okumura MD, PhD & Shoji Natsugoe MD, PhD

  3. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan

    Masaki Mori MD, PhD, FACS

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  1. Yoshiaki Kita MD, PhD
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  2. Koshi Mimori MD, PhD
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  3. Masaaki Iwatsuki MD, PhD
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  4. Takehiko Yokobori MD, PhD
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  5. Keisuke Ieta MD, PhD
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  6. Fumiaki Tanaka MD, PhD
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  7. Hideshi Ishii MD, PhD
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  8. Hiroshi Okumura MD, PhD
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  9. Shoji Natsugoe MD, PhD
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  10. Masaki Mori MD, PhD, FACS
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Corresponding author

Correspondence to Masaki Mori MD, PhD, FACS.

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Kita, Y., Mimori, K., Iwatsuki, M. et al. STC2: A Predictive Marker for Lymph Node Metastasis in Esophageal Squamous-Cell Carcinoma. Ann Surg Oncol 18, 261–272 (2011). https://doi.org/10.1245/s10434-010-1271-1

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  • DOI: https://doi.org/10.1245/s10434-010-1271-1

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