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R.M. Bremnes



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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
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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): R.M. Bremnes

      • 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.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-014 - Positive prognostic impact of miR-210 in non-small cell lung cancer (ID 1537)

      09:30 - 09:30  |  Author(s): R.M. Bremnes

      • Abstract

      Background
      As non-small cell lung cancer (NSCLC) is a leading cause of cancer death, new prognostic and predictive markers are highly warranted. miR-210 is an essential regulator of the hypoxia pathway. The biological and prognostic importance of miR-210 has not been thoroughly studied in NSCLC. We aimed to explore miR-210 expression in both cancer and tumor stromal cells in a large representative NSCLC patient cohort to assess its impact on disease-specific survival (DSS).

      Methods
      Tissue micro arrays (TMAs) were constructed, representing both cancer cells and tumor stromal cells from 335 unselected patients diagnosed with stage I-IIIA NSCLC. In situ hybridization was used to evaluate the expression of miR-210.

      Results
      In univariate analyses, high cancer cell (p=0.039) and high stromal cell expression (p=0.008) of miR-210 were both significantly associated with an improved DSS. Co-expression of miR-210 in cancer and stromal cells combined was also a positive prognostic factor for DSS (p=0.010). In multivariate analysis, miR-210 in stromal cells (p=0.011), and miR-210 co-expressed in cancer and stromal cells (p=0.011) were independent prognosticators for DSS.

      Conclusion
      High expression of miR-210 in tumor stromal cells, and high miR-210 co-expressed in cancer cells and tumor stromal cells mediates an independent favorable prognostic impact in NSCLC. miR-210 may be a candidate marker for prognostic stratification and therapeutic interventions in NSCLC.