Abstract
BackgroundResearchers 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).MethodsThe 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.ResultsOf 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.ConclusionsTo 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.
Highlights
Researchers in recent studies have reported that the sonic hedgehog (Shh) signaling pathway plays a crucial role during tumorigenesis, angiogenesis and cellular differentiation
Normal potions of non-small-cell lung cancer (NSCLC) tissues and negative controls were negative for 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) (Figure 1)
The expression of Shh, Gli1, LYVE-1 and vascular endothelial growth factor (VEGF)-D proteins was found to be related with some clinicopathological factors (Table 5)
Summary
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). The early involvement of the lymphatic system in lung cancer is a probable cause of its poor prognosis, and the presence of lymph node metastasis (N station) is a clinically important prognostic factor that influences therapeutic strategies [5,6]. Tumor cells metastasize to intrapulmonary, mediastinal or extrathoracic lymph nodes [5]. The expression of sonic hedgehog (Shh) and glioma-associated oncogene homolog zinc finger protein 1 (Gli1) has been shown to affect lymphatic metastasis in cancer [10]. The same authors showed that Shh affects the invasion and motility of cancer cells [11]
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