Clinical value of signal transducers and activators of transcription 3 (STAT3) gene expression in human osteosarcoma.
The dysregulation of signal transducers and activators of transcription 3 (STAT3) has been reported to be associated with tumor progression, angiogenesis and metastasis. The purpose of this study was to analyze the clinical value of STAT3 expression in human osteosarcoma. First, semi-quantitative RT-PCR was performed to detect the expression of STAT3 mRNA in normal bone tissues, chondroma tissues and osteosarcoma tissues. Then, immunohistochemistry was performed to detect the expression of STAT3 protein in 76 osteosarcoma tissues and the relationship of STAT3 protein expression with clinicopathologic factors or prognosis of osteosarcoma patients. RNA interference (RNAi) technology was employed to inhibit STAT3 expression. MTT and flow cytometric assays were performed to analyze the effect of STAT3 inhibition on proliferation and apoptosis of osteosarcoma cells. Finally, the expression of STAT3-related target genes were also determined. Results showed that osteosarcoma tissues showed significantly higher expression levels of STAT3 mRNA than normal bone or chondroma tissues (P<0.05). Immunohistochemistry showed that the staining of STAT3 protein was mainly located in cytoplasm of osteosarcoma cells in osteosarcoma tissue samples. The high level of STAT3 protein was associated with poor tumor differentiation and presentation of metastasis (P=0.039 and 0.022). Moreover, the 5-year overall and relapse-free survival rates for osteosarcoma patients with high STAT3 expression were lower than those for patients with low STAT3 expression. In addition, the status of STAT3 protein expression was an independent prognostic factor for both disease-free survival (P=0.0235) and overall survival (P=0.0032). RNAi-mediated STAT3 inhibition could induce proliferation inhibition and apoptosis enhancement in osteosarcoma cells, which might be associated with inhibition of some anti-apoptosis genes. Overall, STAT3 plays crucial roles in osteosarcoma development and might become a potential molecular target for gene therapy of human osteosarcomas.
Wang
Yu-Cai
YC
Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 710038, China. fanqing_2008@yahoo.com.cn
Zheng
Lian-He
LH
Ma
Bao-An
BA
Zhou
Yong
Y
Zhang
Ming-Hua
MH
Zhang
Dian-Zhong
DZ
Fan
Qing-Yu
QY
D000328:Adult; D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002812:Chondroma / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
D012333:RNA, Messenger; D050796:STAT3 Transcription Factor