The effects of sonic hedgehog signaling pathway components on non-small-cell lung cancer progression and clinical outcome

World Journal of Surgical Oncology

Young Ho Choi³  Sang Cheul Oh¹  Hyun Koo Kim³  Yu Hua Quan³  Young A Yoo¹  Myoung Hee Kang¹  Jinwook Hwang² 

[1] 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;Department of Thoracic and Cardiovascular Surgery, Korea University Ansan Hospital, Korea University College of Medicine, 123 Jeokgeum-ro, Danwon-gu, Ansan, Gyeonggi-do 425-707, Republic of Korea;Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, Korea University College of Medicine, 97 Guro-dong kil, Guro-ku, Seoul 152-703, Republic of Korea

关键词: VEGF-D;    Sonic hedgehog;    Prognosis;    NSCLC;    LYVE-1;    Hedgehog pathway;    Gli1;   

Others  :  1148206
DOI  :  10.1186/1477-7819-12-268

 received in 2014-03-22, accepted in 2014-08-06,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Hwang et al.; licensee BioMed Central Ltd.

【 图 表 】

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