Changes of activated circulating endothelial cells and survivin in patients with non-small cell lung cancer after antiangiogenesis therapy.
BACKGROUND
Although antiangiogenesis therapy plays an important role in anti-neoplastic treatment with its recognized efficacy and slight adverse effect, there is no prospective clinical trial to define ideal markers for predicting efficacy of antiangiogenic therapy. This study was undertaken to investigate the changes of activated circulating endothelial cells (aCECs) and survivin after anti-angiogenesis therapy and their significance in predicting the efficacy of the therapy.


METHODS
Patients of non-small cell lung cancer (NSCLC) treated with chemotherapy with or without Endostar were observed. The amount of activated CECs was detected by flow cytometry, and the expression of survivin mRNA was determined by real-time polymerase chain reaction (PCR).


RESULTS
After treatment, the amount of activated CECs decreased significantly in clinical benefit cases (P = 0.021 in chemotherapy alone, P = 0.001 in chemotherapy plus Endostar), increased in disease progressive cases (P = 0.015 in chemotherapy alone, but P = 0.293 in chemotherapy with Endotatar). After therapy, the expression of survivin mRNA decreased in clinical benefit cases (P = 0.001) and increased in disease progressive cases (P = 0.018). A positive correlation was found between activated CECs and survivin in the chemotherapy group pre- and post-therapy (P = 0.001 and 0.021, respectively), but only in the chemotherapy with Endostar group pre-therapy (P = 0.030) rather than post-therapy. A positive correlation was found between the decreased activated CECs after therapy and time to progression (TTP) (r = 0.322, P = 0.012); a negative correlation was found between the amount of survivin mRNA in serum post-therapy and TTP (r = -0.291, P = 0.048).


CONCLUSIONS
Activated CECs and survivin may be ideal markers forecasting efficacy and prognosis of NSCLC. The former can reflect more sensitively antiangiogenic efficacy and the latter is more sensitive to shrinkage or swelling of tumors. Their combination can evaluate more accurately the efficacy of antiangiogenic therapy of NSCLC.
Wang
Jing
J
Tianjin Lung Cancer Center, Key Laboratory of Cancer Prevention and Therapy, Department of Thoracic Oncology, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China.
Huang
Chun
C
Wei
Xi-yin
XY
Qi
Da-liang
DL
Gong
Li-qun
LQ
Mu
Hai-yu
HY
Yao
Qiang
Q
Li
Kai
K
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D043169:Endostatins / Q000627:therapeutic use; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
D020533:Angiogenesis Inhibitors; C107489:BIRC5 protein, human; D043169:Endostatins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; D000077022:Survivin; C522911:endostar protein