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J. Zhang



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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 - 09:30  |  Author(s): J. Zhang

      • Abstract

      Background
      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.

      Methods
      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.

      Results
      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).

      Conclusion
      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).

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    P1.07 - Poster Session 1 - Surgery (ID 184)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P1.07-013 - "Minimally invasive small incision, muscle- and rib-sparing thoracotomy, minimally invasive lung cancer radical surgery", cures "aging, cardiopulmonary dysfunction patients with lung cancer" (ID 1300)

      09:30 - 09:30  |  Author(s): J. Zhang

      • Abstract

      Background
      Developing "minimally invasive small incision, muscle- and rib-sparing thoracotomy (miMRST), minimally invasive lung cancer radical surgery", to cure aging, cardiopulmonary dysfunction patients with lung cancer, who could not tolerate traditional large-incision posterolateral thoracotomy. Typical cases will be discussed here.

      Methods
      Man, aged 64, left lower lobe lesions 1.0cm, localized in central, deep part, not suitable for needle-biopsy, nor for wedge resection; smoking for 44 years, with serious chronic bronchitis 15 years, asthma episodes per year; coronary heart disease 13 years, coronary stenting 10 years; anticoagulation 10 years; serious gastric ulcers, colorectal polyps 2 years. Consulted in hospitals in Shenyang and Beijing for months, advised for follow-up considering his current cardiopulmonary condition and no malignant evidence. Then referral to China Medical University Lung Cancer Center in Dec 26, 2012. Surgical resection was advised at once. Preoperative examination: pulmonary function test revealed airway dysfunction, low blood oxygen. Anti-inflammatory, antispasmodic strategy and preoperative pulmonary function exercise did not improve lung function as expected. The patient was discussed not suitable for regular thoracotomy, unable to tolerate the damage from traditional large-incision posterolateral thoracotomy. “miMRST, minimally invasive lung cancer radical surgery” was scheduled.

      Results
      About 10cm lateral chest incision was enough for most lung cancer resection and mediastinal lymph nodes dissection. Latissimus dorsi and serratus anterior muscles were protected, chest cavity entered through intercostals space, no rib cut. Widespread intrathoracic adhesions, localized severe adhesions, and undifferentiated lung fissures were confirmed. The lesion was found in left lower lobe, adjacent to pulmonary vessels not suitable for wedge resection; swollen lymph nodes adhered around pulmonary vessels were confirmed. Left lower lobe resection, and No.3A,4,5,6,7,8,9,10,11,12,12u,13,14 group regional and mediastinal lymph nodes and surrounding adipose tissue were dissected. When awake after surgery, operative lateral upper limb recovered freedom of movement; the patient got out of bed in the 2nd postoperative day with catheter unplugged in the same day; the chest tube pull out in the 3rd postoperative day; no complications happened. Pathological examination reported lung squamous cell carcinoma, no lymph nodes metastasis. The patient recovered much better and quickly than other patients who received lung cancer resection via traditional standard posterolateral thoracotomy.

      Conclusion
      "miMRST", "minimally invasive small incision, muscle- and rib-sparing thoracotomy, minimally invasive lung cancer radical surgery", shows advantage of small incision, less pain; less damage; quick recovery, better recovery; operative side upper extremity activities early, pulling out catheter early, get out of bed early, being out of ICU early, chest tube pulled out early; stopping antibiotics early, discharge early; no need using expensive rib nails because of no-rib-cut; no need using expensive thoracoscopic vessel staples; almost no complications; significantly less cost. "miMRST ", is minimally invasive thoracic surgery, very suitable for aging, cardiopulmonary dysfunction patients with lung cancer, who could not tolerate traditional large-incision posterolateral thoracotomy. "miMRST ", is also economical, no need using expensive thoracoscopic devices, to some degree, very suitable for lung cancer surgery in developing countries. (This study was partly supported by the Fund for Scientific Research of The First Hospital of China Medical University, No.FSFH1210).

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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
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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. Zhang

      • 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).