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N. Chen

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-012 - A disintegrin and metalloproteinase-9 is highly expressed, correlated with lymph nodes metastasis, predicts worse prognosis and may help improving personalized postoperative treatment in resected non-small cell lung cancer (ID 1296)

      09:30 - 16:30  |  Author(s): N. Chen

      • Abstract

      Recently we found a disintegrin and metalloproteinase-9 (ADAM9) was highly expressed in resected stage Ⅰ non-small cell lung cancer (NSCLC), correlated with shorterned survival time. Here, we investigate the abnormal expression of ADAM9 in surgically resected advanced NSCLC, to elucidate the relationship between ADAM9 expression and lymph node metastasis, to further evaluate the significance of ADAM9 as a novel biomarker in predicting the prognosis, and predicting the necessity of personalized postoperative chemo-radiation for the resected NSCLC.

      One hundred and twenty eight cases of completely resected stage Ⅰ, Ⅱ and Ⅲ NSCLC with mediastinal N2 lymph nodes dissected were immunohistochemically analyzed for ADAM9 protein expression. Survival analysis were conducted to asses the significance of ADAM9 expression and the relationship with other clinicopathological characteristics.

      Of the 128 NSCLC, 64 were stage Ⅰ, 19 stage Ⅱ and 45 stage Ⅲ; 66.4% (85/128) was found with ADAM9 protein highly expressed (ADAM9+), significantly higher when compared with normal control lung tissues (P=0.000). The ADAM9+ rate in adenocarcinoma was higher than in squamous cell carcinoma (75.5% vs 41.2%) (P=0.000). ADAM9+ rates in stage Ⅱ and Ⅲ NSCLC were 84.2% and 77.8%, respectively, significantly higher than 53.1% in stage Ⅰ (P=0.006). Stratified, ADAM9+ rates in N1 and N2 cases were 76.2% and 80.6%, respectively, significantly higher than 56.3%, the ADAM9+ rate in N0 NSCLC (P=0.025). There was no difference found between ADAM9+ rates in T factor groups (P>0.05). The overall 5-year survival rate was 54.6% for this group of 128 completely resected NSCLC. The 5-year survival rate in ADAM9 low expression (ADAM9-) group (43 cases) was 68.8%, however, the 5-year survival rate was sharply decreased to 47.7% in ADAM9+ group (85 cases), the difference was statistically significant (P=0.039). Linear correlation analysis discovered that the ADAM9 expression showed a significantly negative correlation with the survival time of the 128 cases of resected NSCLC (R=-0.217, P=0.014). Patients who received postoperative chemo-radiation therapy (41 cases) had a higher 5-year survival rate of 69.5% when compared with those who received surgery only but without adjuvant chemo-radiation (87 cases) whose 5-year survival was 47.9% (P=0.017). When stratified, in the 85 ADAM9+ cases, the 5-year survival rate for those who received postoperative chemo-radiation therapy was 63.7%, higher than 40.4% who did not receive adjuvant chemo-radiation (P=0.037); however, in the ADAM9- cases, postoperative chemo-radiation did not improve the 5-year survival rate with a statistic significance (P=0.198).

      ADAM9 is highly expressed in human resected non-small cell lung cancer tissues, correlated with lymph nodes metastasis and pTNM stage; highly expressed ADAM9 predicts worse prognosis, suggesting that ADAM9 is a useful novel prognostic biomarker. Importantly, ADAM9 could become a novel useful predictive biomarker helping decide if postoperative chemo-radiation therapy should be selected or not; adjuvant chemo-radiation therapy might benefit ADAM9+ NSCLC much more, instead of ADAM9- NSCLC. (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).