This study was to investigate whether the expression of a disintegrin and metalloproteinase-9 (ADAM9) is correlated with the expression of hepatoma-derived growth factor (HDGF) in surgically resected non-small cell lung cancer (NSCLC), to evaluate the significance of HDGF and ADAM9 as novel molecular staging biomarkers, prognostic biomarkers and predictive biomarkers for postoperative adjuvant chemotherapy in surgically resected stage I NSCLC, to provide essential consistence proof to the possible novel pathway of HDGF–ADAM9 pathway.
Sixty-three cases of resected stage I NSCLC with mediastinal N2 lymph node dissection were immunohistochemically analyzed for HDGF and ADAM9 protein expression. Multivariate analysis and survival analysis were conducted.
HDGF and ADAM9 were observed highly expressed in NSCLC compared with normal control lung tissues (P < 0.05). HDGF high expression cases showed significantly lower survival rate (55.6 vs. 84.7 %, P = 0.009). HDGF high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.015). ADAM9 high expression cases showed significantly lower survival rate (56.9 vs. 88.7 %, P = 0.015). ADAM9 high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.021). Pearson’s correlation analysis revealed that ADAM9 expression was correlated positively and significantly with HDGF expression in 63 cases of stage I NSCLC (r = 0.547, P = 0.000).
These results clearly demonstrate that ADAM9 high expression is correlated positively and significantly with HDGF high expression, which provides essential evidence for the novel HDGF–ADAM9 pathway, through which HDGF promotes invasion and metastasis of NSCLC cells; HDGF and ADAM9 are novel molecular staging biomarkers, prognostic biomarkers, which might become useful predictive biomarkers for the selection of postoperative adjuvant chemotherapy treatment in surgically resected stage I NSCLC.
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The authors wish to thank C. Guan for technical assistance of immunohistochemistry staining, Dr. Y. Han and Dr. A. He for immunostaining evaluation and discussion. The authors appreciate Mr. Philip Whatley for copyediting the manuscript. This study was supported in part by IASLC/CRFA Prevention Fellowship, grants from The Education Department of Liaoning Province (No. 20060991) and from the Nature Science Foundation of Liaoning Province, China (No. 20102285), and Fund for Scientific Research of The First Hospital of China Medical University (No. FSFH1210).
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The authors have no potential conflicts of interest.
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Zhang, J., Chen, N., Qi, J. et al. HDGF and ADAM9 are novel molecular staging biomarkers, prognostic biomarkers and predictive biomarkers for adjuvant chemotherapy in surgically resected stage I non-small cell lung cancer. J Cancer Res Clin Oncol 140, 1441–1449 (2014). https://doi.org/10.1007/s00432-014-1687-2
- Lung cancer
- Prognostic biomarker
- Molecular staging biomarker