IGF2R expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC.
BACKGROUND
Insulin-like growth factor (IGF) pathway has been suggested as a new molecular target for the treatment of cancer including Non-small cell lung cancer (NSCLC). We postulated that IGF-2 receptor (IGF2R) may be associated with treatment response and prognosis of NSCLC patients receiving chemotherapy.


METHODS
A total of 464 patients with inoperable advanced stage of NSCLC were enrolled. All patients received platinum-based chemotherapy. Meanwhile, the IGF2R expression in tumor samples was detected by Immunohistochemical analysis. The IGF2R expression was inhibited in several human NSCLC cell lines (H292, A549, NCI-H460, Calu-3 and NCI-H23) after small interfering RNA (siRNA) transfection and the cellular biology behavior were evaluated.


RESULTS
Of all NSCLC patients, 204 had high IGF2R expression and 260 had low IGF2R expression. The low IGF2R expression was significantly associated with the smoking status, higher tumor stage, and poorer differentiation status of these patients. Notably, we found that the low IGF2R expression was closely associated with the chemotherapy response in NSCLC patients. Patients with low IGF2R expressions had a poorer prognosis than those with high IGF2R expressions. IGF2R inhibition by si-RNA technique in NSCLC cell lines increased the proliferation, migration and invasion abilities, but reduced the apoptosis rate. IGF2R silencing significantly enhanced the chemo-resistance of NSCLC cell lines to cisplatin treatment.


CONCLUSIONS
The IGF2R expression in tumor is associated with the chemotherapy response and prognosis of Patients with advanced NSCLC.
Department of Pathology, The Third Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, China.
Zhennan
Z
Tian
Guodong
G
Yao
Hongtao
H
Song
Yang
Y
Zhou
Jingshu
J
Geng
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics*
D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2; D002945:Cisplatin