Home » Key Scientific Articles » High expression of a disintegrin and metalloproteinase-9 predicts a shortened survival time in completely resected stage I non-small cell lung cancer.

High expression of a disintegrin and metalloproteinase-9 predicts a shortened survival time in completely resected stage I non-small cell lung cancer.

Zhang J, Qi J, Chen N, Fu W, Zhou B, He A.

Oncol Lett. 2013 May;5(5):1461-1466.

Department of Molecular Targeted Therapeutics, China Medical University Lung Cancer Center, The First Hospital of China Medical University, Shenyang, P.R. China ; Department of Thoracic Surgery 1, China Medical University Lung Cancer Center, The First Hospital of China Medical University, Shenyang, P.R. China.

 

Abstract

 

The aim of this study was to investigate the abnormal expression of a disintegrin and metalloproteinase-9 (ADAM9) in human resected non-small celllung cancer (NSCLC) tissue, in order to evaluate the significance of ADAM9 expression in surgically resected NSCLC. Sixty-four cases of completelyresected stage I NSCLC with mediastinal N2 lymph node dissection were immunohistochemically analyzed for ADAM9 protein expression. Survival, univariate and multivariate analyses were conducted to assess the significance of ADAM9 expression and its correlation with other clinicopathological characteristics. ADAM9 was observed to be significantly more highly expressed in NSCLC tissue compared with normal control lung tissue (P=0.001). The 5-year survival rate for patients with NSCLC tissues highly expressing ADAM9 was significantly lower when compared with NSCLC tissues of patients exhibiting low expression of ADAM9 (56.9 vs. 88.9%, P= 0.012). Multivariate analysis identified that high expression of ADAM9 is an independent factor of shortened survival time in resected stage I NSCLC (HR, 3.385; 95% CI, 1.224-9.360; P=0.019). These results clearly demonstrate that ADAM9 is highly expressed in NSCLC and highly expressed ADAM9 correlates with shortened survival time, suggesting that ADAM9 is a novel biomarker for predicting prognosis in resected stage I NSCLC. ADAM9 may also become a useful predictive biomarker for the selection of adjuvant chemotherapy treatment of NSCLC.

 

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Additional Information: 

Dr. Jun Zhang is from China Medical University Lung Cancer Center, the First Hospital of China Medical University (CMU), Shenyang, China.

Besides developing minimally invasive video-assisted thoracoscopy surgery (VATS) for lung cancer patients in the First Hospital of CMU, Dr. Jun Zhang has been developing “Minimally invasive small incision (10cm), muscle- and rib-sparing thoracotomy (miMRST),  minimally invasive lung cancer radical surgery”, to provide a “minimally invasive” lung cancer surgery, but not as expensive as VATS is; a “minimally invasive” thoracotomy, meanwhile being able to ensure mediastinal lymph nodes and surrounding adipose  tissues being dissected completely as traditional large-incision posterolateral thoracotomy  does. “miMRST”, is suitable for most lung cancer cases, but costs less.

Dr. Jun Zhang’s laboratory research interests are to develop translational research work, to investigate the molecular mechanism of cell growth, invasion and metastasis of lung cancer cells. Recently, Dr. Jun Zhang and his team are focusing on that hepatoma-derived growth factor (HDGF) promotes cell growth and invasion of non-small cell lung cancer (NSCLC) cells. When HDGF siRNA-silenced, anchorage-independent growth of NSCLC cells could be significantly inhibited, and the ability of NSCLC cells to invade across a BD Matrigel membrane barrier could also be significantly inhibited, which clearly suggested HDGF’s important role in cell growth, invasion and metastasis of NSCLC. PEI-mediated siRNA-targeting-HDGF treatment (administered intra-peritonea) could significantly inhibit growth and invasion of subcutaneous xenograft NSCLC tumors, suggested HDGF’s importance as a valuable target for molecular targeted therapy to improve NSCLC treatment.

Interestingly, HDGF and down-stream genes, such as a disintegrin and metalloproteinase-9 (ADAM9), were found highly expressed in human surgically resected NSCLC, correlated with worse prognosis, predictive to the necessity of postoperative adjuvant chemo-radiation. Dr. Jun Zhang and his team are designing prospective studies to confirm HDGF and ADAM9’s clinical significance as novel prognostic biomarkers, molecular staging biomarkers, and importantly, as novel predictive biomarkers for the decision of postoperative adjuvant chemo-radiation, helping improve personalized postoperative treatment in resected NSCLC.

 

High expression of a disintegrin