Overexpression of Ang-2 mRNA in non-small cell lung cancer: association with angiogenesis and poor prognosis.
Overexpressed Angiopoietin-2 (Ang-2) derived mainly from cancer cells was reported to promote tumor angiogenesis. The aim of this study was to evaluate the expression of Ang-2 in non-small cell lung cancers (NSCLCs). We investigated Ang-2 expression in 77 patients with NSCLC who underwent curative tumor resection by means of reverse transcription-polymerase chain reaction (RT-PCR). We also determined whether or not expression of Ang-2 mRNA correlates with immunohistochemical assays of Ang-2 protein and microvessel density (MVD) level. The level of Ang-2 mRNA expression was presented by the relative yield of each gene to the S14 mRNA, respectively. Ang-2 mRNA expression in NSCLC was significantly greater than that in non-cancerous normal lung (p=0.0178). The Ang-2 mRNA expression was significantly associated with lymph node metastasis, stage, Ang-2 protein, and microvessel density (MVD) level (p=0.0009 for lymph node metastasis; p=0.0002 for stage; p<0.0001 for Ang-2 protein; p<0.0001 for MVD). With regard to prognosis, the overall and stage I survival rates for patients in the high Ang-2 mRNA expression group were significantly poorer when compared with the low Ang-2 mRNA expression group (p<0.0001 for overall; p=0.0201 for stage I). Furthermore, expression of Ang-2 mRNA was an independent predictor of prognosis by multivariate analysis (p=0.0028). These data indicate that Ang-2 may contribute to tumor angiogenesis and progression and that Ang-2 gene expression can serve as a useful prognostic marker in NSCLC.
Takanami
Iwao
I
Department of Surgery, Teikyo University School of Medicine, Tokyo 173, Japan. takanami@med.teikyo-u.ac.jp
D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism*; D018287:Carcinoma, Large Cell / Q000098:blood supply / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011379:Prognosis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014157:Transcription Factors
D042702:Angiopoietin-2; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C051065:THRSP protein, human; D014157:Transcription Factors