Synaptonemal complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer patients with lymph node metastasis

Haruhisa Kitano, Joon Yong Chung, Kyung Hee Noh, Young Ho Lee, Tae Woo Kim, Seok Hyung Lee, Soo Heang Eo, Hyung Jun Cho, Chel Hun Choi, Shuhei Inoue, Jun Hanaoka, Junya Fukuoka, Stephen M. Hewitt

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6 Citations (Scopus)

Abstract

Background: The interaction of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGF receptor-3 is considered to be a major driver of lymphangiogenesis, however the mechanism of this process remains unclear. We aimed to investigate the possible lymphangiogenic significance of synaptonemal complex protein 3 (SCP3) in non-small cell lung cancer (NSCLC). Methods: The expression of SCP3, VEGF-C, and VEGF-D were measured and examined a correlation between SCP3 and VEGF-C or VEGF-D in various human lung cancer cell lines. Subsequently, we assessed SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D expression in archival tumor tissues from 89 NSCLC patients with lymph node (LN) metastasis by combined immunohistochemistry with quantitative digital image analysis. Results: Positive correlations between SCP3 and VEGF-C expression (R2 = 0.743) and VEGF-D expression (R2 = 0.932) were detected in various human lung cancer cell lines. The high expression of SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D were detected in 24 (27.0%), 22 (24.7%), 27 (30.3%), 27 (30.3%), and 24 cases (27.0%), respectively. Notably, SCP3 positively correlated with VEGF-C and VEGF-D expression (for both, P < 0.001) and negatively correlated with VEGF-A and VEGF-B expression (P = 0.029 and P = 0.026, respectively). In multivariate analysis of patients with LN metastasis, SCP3 expression predicted worse overall survival (hazard ratio = 1.86, P = 0.008). Conclusions: SCP3 is associated with lymphangiogenesis and provides insight into the SCP3-VEGF-C/VEGF-D axis based cancer therapy strategy.

Original languageEnglish
Article number138
JournalJournal of Translational Medicine
Volume15
Issue number1
DOIs
Publication statusPublished - 2017

Keywords

  • Lymph node metastasis
  • Lymphangiogenesis
  • Non-small cell lung cancer
  • SCP3
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Kitano, H., Chung, J. Y., Noh, K. H., Lee, Y. H., Kim, T. W., Lee, S. H., Eo, S. H., Cho, H. J., Choi, C. H., Inoue, S., Hanaoka, J., Fukuoka, J., & Hewitt, S. M. (2017). Synaptonemal complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer patients with lymph node metastasis. Journal of Translational Medicine, 15(1), [138]. https://doi.org/10.1186/s12967-017-1241-5