Correlation between CXCR4/CXCR7/CXCL12 chemokine axis expression and prognosis in lymph-node-positive lung cancer patients

Masakazu Katsura, Fumihiro Shoji, Tatsuro Okamoto, Shinichiro Shimamatsu, Fumihiko Hirai, Gouji Toyokawa, Yosuke Morodomi, Tetsuzo Tagawa, Yoshinao Oda, Yoshihiko Maehara

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13 Citations (Scopus)

Abstract

The CXCR4/CXCR7/CXCL12 chemokine axis plays important roles in the migration of tumor cells during cancer development by modulating site-specific distant metastasis including to regional lymph nodes. We investigated the correlation of these chemokine expressions to prognosis in lymph-node-positive non-small-cell lung cancer (NSCLC) patients. A total of 140 surgically resected specimens of primary site (PS) and metastatic lymph nodes (MLN) of NSCLC involving hilar and/or mediastinal lymph nodes (N1-2) were collected. CXCR4, CXCR7 and CXCL12 expressions were evaluated. Cox regression analysis was performed to determine whether these chemokines were independent prognostic factors in N1-2 NSCLC. High expression of CXCR4 in PS and CXCL12 in MLN was associated with poor overall survival (OS) (P =.025 and.033, respectively). Significant correlations between CXCR4 expression in PS and CXCL12 expression in MLN were observed (P =.040). There was significant difference in OS between 2 groups according to expressions of CXCR4 in PS and CXCL12 in MLN (P =.0033). Expression of CXCL12 in MLN was identified as an independent prognostic factor (HR 1.79, 95% CI 1.08-3.04, P =.023). CXCL12 in MLN was mainly expressed by tumor cells compared with stromal cells (56% vs 25%, respectively, P <.0001). CXCR4/CXCL12 may play roles in tumor progression in MLN and is associated with poor prognosis of lymph-node-positive NSCLC patients.

Original languageEnglish
Pages (from-to)154-165
Number of pages12
JournalCancer Science
Volume109
Issue number1
DOIs
Publication statusPublished - Jan 2018

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Katsura, M., Shoji, F., Okamoto, T., Shimamatsu, S., Hirai, F., Toyokawa, G., Morodomi, Y., Tagawa, T., Oda, Y., & Maehara, Y. (2018). Correlation between CXCR4/CXCR7/CXCL12 chemokine axis expression and prognosis in lymph-node-positive lung cancer patients. Cancer Science, 109(1), 154-165. https://doi.org/10.1111/cas.13422