Author of

• 11481

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  P2.02 - Poster Session 2 - Novel Cancer Genes and Pathways (ID 148)

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

  • 11488

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    P2.02-007 - HDGF, ADAM9 involved in a novel pathway of cell growth and invasion of non-small cell lung cancer cells, may become novel molecular staging biomarkers, prognostic and predictive biomarkers of NSCLC (ID 1297)

    11:12 - 11:29  |  Author(s): J. Qi
    • Abstract

    Background
    Our recent studies revealed that hepatoma-derived growth factor (HDGF) was highly expressed in non-small cell lung cancer (NSCLC) cells, when HDGF targeted-silenced by siRNA strategy, anchorage-independent growth of NSCLC cells can be significantly inhibited, the ability of NSCLC cells to invade across BD Matrigel membrane barrier can also be significantly inhibited, clearly suggested HDGF’s important role in cell growth, invasion and metastasis of NSCLC. However, the molecular mechanism is still undiscovered. Here, we reported that HDGF-ADAM9…may be the novel pathway for HDGF promotes growth and invasion of NSCLC cells. The expression of HDGF, ADAM9 in human resected NSCLC tissues will be detected, and the co-relationship, coordination of HDGF and ADAM9 will be evaluated to provide evidence, to elucidate the logic possibility of the HDGF-ADAM9…pathway.

    Methods
    siRNAs targeting HDGF were designed, used for specifically silencing HDGF in NSCLC cells. In vitro and in vivo cell growth and invasion assay were conducted. cDNA microarray and Western blot were used to explore the novel pathway, the possible molecular mechanism, by which HDGF promotes growth and invasion of NSCLC cells. Immunohistochemical SP method was used to detect the expression of HDGF and down-stream modulated genes in NSCLC tissues. Multivariate analysis and survival analysis were conducted to evaluate the clinical significance, the co-relationship, the possible coordination of HDGF and down-stream genes.

    Results
    Western blot revealed that HDGF protein expression in NSCLC cells were down-regulated more than 90% after silenced by targeted siRNA; anchorage-independent growth of A549 and H226 cells were inhibited significantly (P=0.000, 0.003, respectively); the ability of invading across BD Matrigel membrane barrier were inhibited significantly (P=0.004, 0.000, respectively). cDNA microarray revealed that a panel of genes, including AXL, GLO1, and ADAM9, were significantly down-regulated when HDGF was silenced by siRNA, suggested the possible pathways in which HDGF was involved. The expression of HDGF and ADAM9 were Immunohistochemically detected in 63 cases of completely resected stage Ⅰ NSCLC, found highly expressed in NSCLC when compared with normal control lung tissues (P=0.003, 0.001, respectively); highly expressed HDGF and ADAM9 were found correlated with significantly declined 5-year survival rates (P=0.009, 0.015, respectively). HDGF expression was revealed correlated positively and significantly with ADAM9 expression in these resected stage Ⅰ NSCLC (Pearson r=0.547, P=0.000).

    Conclusion
    These results clearly revealed that HDGF may promote cell growth and invasion of NSCLC cells via ADAM9 pathway, HDGF-ADAM9…should be a novel pathway of lung cancer invasion and metastasis. High expression of HDGF and ADAM9 correlate with shortened survival time, predict lower 5-year survival rates, suggesting that HDGF and ADAM9 are novel biomarkers for predicting prognosis in resected stage Ⅰ NSCLC, revealing their significance as novel molecular staging biomarkers. HDGF and ADAM9 may also become useful predictive biomarkers for the selection of adjuvant chemotherapy treatment of NSCLC to improve personalized postoperative treatment in resected stage Ⅰ non-small cell lung cancer. (This study was partly supported by grant from the Nature Science Foundation of Liaoning Province, China, No.20102285; and the Fund for Scientific Research of The First Hospital of China Medical University, No.FSFH1210).