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.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
China Medical University Lung Cancer Center, The First Hospital of China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang, 110001, People's Republic of China, JunZhang@mail.cmu.edu.cn.
Jun
J
Zhang
Ning
N
Chen
Juan
J
Qi
Baosen
B
Zhou
Xueshan
X
Qiu
D051722:ADAM Proteins / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models
D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C051610:hepatoma-derived growth factor; D051722:ADAM Proteins; C098339:ADAM9 protein, human