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  P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11568

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    P2.06-025 - Prognostic impact of CXCL16 and CXCR6 in two non-small cell lung cancer cohorts: combined high stromal and tumor cell CXCL16 expression yields an improved survival (ID 2194)

    09:30 - 09:30  |  Author(s): S.M. Hald
    • Abstract

    Background
    The chemokine CXCL16 and its receptor CXCR6 are expressed on a variety of immune cells, and have been shown to influence angiogenesis. Hence, these markers are potentially interesting markers in NSCLC treatment. The expression of CXCR6 and CXCL16 has been examined in a variety of human cancers; however no studies have investigated their influence on prognosis in non-small cell lung cancer (NSCLC). We therefore wanted to explore their prognostic significance in NSCLC, in addition to examining associations with our previously investigated immunologic and angiogenic markers.

    Methods
    Resected tumor tissue from consecutive unselected stage I-IIIA NSCLC patients (1990-2005) were collected in two different cohorts; Nordland Central Hospital, NCH (n = 176), and University Hospital of North Norway, UNN (n = 159). Tissue microarrays were constructed from duplicate cores of neoplastic epithelial and stromal areas of each specimen. Immunohistochemistry was used to evaluate the expression of CXCR6 and CXCL16. Correlation analyses with well-known adaptive immunological (CD4, CD8, CD20), innate immunological (CD68, CD56, CD1A) and angiogenic (vascular endothelial growth factors and receptors, platelet derived growth factors and receptors and fibroblast growth factor-2 and receptor-1) markers were done. Disease-specific survival was used as endpoint, and survival analyses were performed in each cohort separately and in the combined total population.

    Results
    In univariate analysis, ↑stromal cell CXCL16 expression was a significant positive prognostic factor in the combined patient cohort (P = 0.016), supporting the similar trends in each cohort separately (NCH, P = 0.045; UNN, P = 0.137). Interestingly, the combinations (Figure 1) increased (↑stromal and ↑cancer cell), mixed (↑↓ and ↓↑) and reduced (↓stromal ↓cancer cell) CXCL16 expression patterns showed 5-year survival rates of 71%, 58% and 48%, respectively (P = 0.016). CXCR6 was expressed in cancer cells, but did not show any significant prognostic impact. There were no strong correlations between CXCR6/CXCL16 and immunological or angiogenic markers. In the multivariate analysis, combined ↓cancer and ↓stromal cell CXCL16 expression was an independent negative prognostic factor in the total cohort when compared to ↑stromal and ↑cancer cell expression (hazard ratio: 2.41; 95% confidence interval: 1.14 – 5.12, P = 0.022). Figure 1

    Conclusion
    We have shown that combined ↑cancer and ↑stromal cell CXCL16 expression is an independent positive prognostic factor in NSCLC. Further studies are warranted to elucidate the biological mechanism underlying this finding.