title: The effects of sonic hedgehog signaling pathway components on non-small-cell lung cancer progression and clinical outcome.
abstract: BACKGROUND
  Researchers in recent studies have reported that the sonic hedgehog (Shh) signaling pathway plays a crucial role during tumorigenesis, angiogenesis and cellular differentiation. We investigated the clinical and pathological significances of the Shh pathway and of its lymphangiogenic components in non-small-cell lung cancer (NSCLC), namely, Shh, glioma-associated oncogene homolog zinc finger protein 1 (Gli1), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and vascular endothelial growth factor D (VEGF-D).
  
  
  METHODS
  The expression of Shh, Gli1, LYVE-1 and VEGF-D in primary NSCLC tissue from 40 patients was examined using immunohistochemical assays, and relationships between expression and clinicopathological data, such as age, gender, histology, tumor size, nodal stage, visceral pleural invasion, lymphatic thromboembolism, recurrence and overall survival were investigated.
  
  
  RESULTS
  Of the 40 specimens examined, 25 (62.5%), 20 (50.0%), 11 (27.5%) and 20 (50.0%) were positive for Shh, Gli1, LYVE-1 or VEGF-D expression, respectively. The expression of Gli1 and LYVE-1 were significantly associated (P = 0.011), and Shh and LYVE-1 expression was related to visceral pleural invasion and lymphatic thromboembolism, respectively (P < 0.05). Shh expression levels compared on survival curves were statistically significant in univariate logrank analysis (P = 0.020). However, other clinicopathological factors did not reveal any statistical significance in univariate and multivariate analyses.
  
  
  CONCLUSIONS
  To our knowledge, this the first report of the relationship between components of the Shh signaling pathway and prognosis in NSCLC. The expression of Shh, Gli1 and LYVE-1 was found to be associated with clinicopathological factors and survival. Thus, the overexpression of the Shh signaling pathway could serve as a predictor of malignant behavior, including lymphangiogenesis, in NSCLC.
authors.forename: Jinwook
authors.initials: J
authors.lastname: Hwang
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kang
authors.forename: Young A
authors.initials: YA
authors.lastname: Yoo
authors.forename: Yu Hua
authors.initials: YH
authors.lastname: Quan
authors.affiliation: Division of Oncology/Hematology, Departments of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, 97 Guro-dong kil, Guro-ku, Seoul 152-703, Republic of Korea. kimhyunkoo@korea.ac.kr.
authors.forename: Hyun Koo
authors.initials: HK
authors.lastname: Kim
authors.forename: Sang Cheul
authors.initials: SC
authors.lastname: Oh
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D042583:Lymphangiogenesis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate; D013923:Thromboembolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C119248:LYVE1 protein, human; D012333:RNA, Messenger; C509239:SHH protein, human; D014157:Transcription Factors; D042643:Vascular Endothelial Growth Factor D; D033921:Vesicular Transport Proteins; D000071676:Zinc Finger Protein GLI1