Expressions of sonic hedgehog, patched, smoothened and Gli-1 in human intestinal stromal tumors and their correlation with prognosis

Yoshizaki, Ayumi; Nakayama, Toshiyuki; Naito, Shinji; Wen, Chun-Yang; Sekine, Ichiro

doi:10.3748/wjg.v12.i35.5687

Cited by 27 publications

(35 citation statements)

References 30 publications

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“…Recent years, the prognostic value of hedgehog components in some tumor types was reported (22)(23)(24)(25)(26). In the present study, we clearly show that many genes of hedgehog signaling upregulated in clinical ICC samples.…”

Section: Discussionsupporting

confidence: 69%

The Prognostic Significance and Therapeutic Potential of Hedgehog Signaling in Intrahepatic Cholangiocellular Carcinoma

Tang

Tan

Jiang

et al. 2013

Clinical Cancer Research

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Purpose: The correlation of the hedgehog signaling pathway with the progression, prognosis, and therapeutics of intrahepatic cholangiocellular carcinoma (ICC) has not been well documented. The study aimed to investigate the expression, prognostic significance, and therapeutic value of hedgehog components in ICC.Experimental Design: Two independent cohorts of 200 patients with ICC were enrolled. By real-time PCR and immunohistochemistry assay, hedgehog components expression was evaluated. The prognostic values of hedgehog proteins were identified and verified. Cyclopamine or siRNA-targeting Gli was used to block the hedgehog signaling. Cell proliferation and apoptosis were observed by CCK8, cell cycle, and annexin V staining assays. In vivo murine tumor model was used to evaluate the role of hedgehog in ICC.Results: In ICC tissues, the Gli1 nuclear immune-intensity was associated with intrahepatic metastasis and the expression of Gli2 was associated with intrahepatic metastasis, venous invasion, and Unio Internationale Contra Cancrum (UICC) pT characteristics. In survival analysis, high Gli1 or Gli2 expressers had an unfavorable overall survival (OS) prognosis and a shorter disease-free survival (DFS) than those with low expression. In multivariate analysis, Gli1 expression was found to be an independent prognostic factor of OS, which was validated by another independent cohort. Furthermore, blocking the hedgehog signaling by cyclopamine or siRNA-targeting Gli1 resulted in apoptosis and growth inhibition in ICC cells.Conclusions: This study shows, for the first time, activation of hedgehog pathway associated with the progression and metastasis in ICC, which may provide prognostic and therapeutic values for this tumor.

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Section: Discussionsupporting

confidence: 69%

The Prognostic Significance and Therapeutic Potential of Hedgehog Signaling in Intrahepatic Cholangiocellular Carcinoma

Tang

Tan

Jiang

et al. 2013

Clinical Cancer Research

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“…In other malignancies PTCH1 expression was correlated with high grade and advanced stage tumors suggesting that HH signaling may differentially affect tumor biology depending on the tissue context [9,41]. We also showed that SMO was overexpressed in NSCLC consistently with studies in other tumors [39,41,42]. Its expression differed among NSCLC types, being higher in squamous cell carcinomas similarly to PTCH1.…”

Section: Discussionsupporting

confidence: 68%

Overexpression of hedgehog pathway molecules and FOXM1 in non-small cell lung carcinomas

et al. 2009

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“…These data further implicate the Hh signaling pathway in prostate cancer progression. Reduced SHH is of interest because many clinical and scientific studies have reported that elevated SHH levels correlate with poor survival in patients or animals in various tumor types, including prostate cancer (17,(47)(48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

Protease nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma

McKee

Xu²,

Cao³

et al. 2012

J. Clin. Invest.

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Expressions of sonic hedgehog, patched, smoothened and Gli-1 in human intestinal stromal tumors and their correlation with prognosis

Abstract: These results suggest that the Hh signaling pathway may play an important role in myogenic differentiation and the malignant potential of human intestinal stromal tumors.

Cited by 27 publications

References 30 publications

The Prognostic Significance and Therapeutic Potential of Hedgehog Signaling in Intrahepatic Cholangiocellular Carcinoma

The Prognostic Significance and Therapeutic Potential of Hedgehog Signaling in Intrahepatic Cholangiocellular Carcinoma

Overexpression of hedgehog pathway molecules and FOXM1 in non-small cell lung carcinomas

Protease nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma

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