Gli1, a potential regulator of esophageal cancer stem cell, is identified as an independent adverse prognostic factor in esophageal squamous cell carcinoma

Yang, Zheng; Cui, Yan; Ni, Weidong; Kim, Seokhyung; Xuan, Yanhua

doi:10.1007/s00432-016-2273-6

Cited by 42 publications

(38 citation statements)

References 25 publications

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“…They further showed that GLI-1 expression correlated directly with important cancer stem cell markers, including SOX9 and CD44 that are involved in epithelial-tomesenchymal transition (EMT). 16,17 Interestingly, Yang and colleagues found a positive GLI-1 expression in 28.3% of all cases, which correlated with the expression pattern of SMO (35.6%). In our cohort we have also demonstrated a direct correlation between SMO and GLI-1 expression, but in contrast to Yang, GLI-1 expression was no significant indicator of worse overall or disease-free survival.…”

Section: Discussionmentioning

confidence: 92%

“…demonstrated that high GLI‐1 expression was associated with inferior outcome. They further showed that GLI‐1 expression correlated directly with important cancer stem cell markers, including SOX9 and CD44 that are involved in epithelial‐to‐mesenchymal transition (EMT) . Interestingly, Yang and colleagues found a positive GLI‐1 expression in 28.3% of all cases, which correlated with the expression pattern of SMO (35.6%).…”

Section: Discussionmentioning

confidence: 96%

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Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

et al. 2019

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AimsBecause the hedgehog signalling pathway plays a major role in many types of cancer and can nowadays be targeted by specific compounds, we aimed to investigate the role of this pathway in squamous cell carcinoma of the head and neck.Methods and resultsNinety‐eight treatment‐naive head and neck cancer specimens were immunohistologically stained for SMO, GLI‐1, p53 and p16 expression and correlated with clinicopathological factors. Immunoreactivity for SMO and GLI‐1 was found in 20 (20.4%) and 52 (53.1%) cases of tumours, respectively. SMO expression correlated with GLI‐1 expression (ρ = 0.258, P = 0.010) in univariate and multivariate analysis (P = 0.007, t = 2.81). In univariate analysis, high SMO expression was associated with shorter overall survival (HR = 0.56; 95% CI = 0.32–0.98; P = 0.044) and disease‐free survival (HR = 0.53; 95% CI = 0.30–0.95; P = 0.034). In multivariate cox regression analysis SMO expression showed a trend towards an independent predictor for shorter overall survival (HR = 0.57; 95% CI = 0.30–1.05; P = 0.072) and disease‐free survival (HR = 0.53; 95% CI = 0.28–1.02; P = 0.056). In head and neck cancer patients with low tumour p16 expression, SMO expression was an independent factor for overall survival (HR = 0.49; 95% CI = 0.24–0.98; P = 0.043) and disease‐free survival (HR = 0.45; 95% CI = 0.22‐0.96; P = 0.037).ConclusionAlthough it needs to be confirmed in larger cohorts, our results suggest that targeting SMO might be a potentially therapeutic option in patients with head and neck cancer. In line, molecular pathological analyses including mutation analysis in the hedgehog pathway might point to additional therapeutic leads.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

et al. 2019

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“…IHC staining and evaluation of the IHC analysis on CRC tissue microarray samples was performed as previously described [8]. The primary antibody include anti-TNC (1:100, Abcam, UK), anti-SOX2 (1:100, Abcam, UK), anti-CD44 (1:80, Millipore, USA), anti-CD133 (1:100, NOVUS, USA), anti-LSD1 (1:250, Sigma, USA), anti-SOX9 (1:100, Abnova, USA), anti-p21 (1:100, Millipore, USA), anti-cyclinD1 (1:100, Millipore, USA), anti-p27 (1:100, Millipore, USA), anti-CDK4 (1:100, Millipore, USA), anti-p16 (1:100, Millipore, USA), anti-SMO (1:250, Santa, USA), and anti-GLI1 (1:100, Abcam, UK).…”

Section: Immunohistochemical (Ihc) Staining Proceduresmentioning

confidence: 99%

“…Western blot analysis were carried out according to the standard procedures [8] for anti-TNC (1:1000, Abcam, UK), anti-LSD1 (1:2000, Sigma, USA), anti-SOX2 (1:1000, Abcam, UK), anti-CD44 (1:1000, Millipore, USA), anti-CD133 (1:1000, NOVUS, USA), anti-SOX9 (1:1000, Abnova, USA), anti-GLI1 (1:1000, Abcam, UK), and anti-β-actin (1:500, Bioss, China).…”

Section: Western Blotting Analysismentioning

confidence: 99%

Tenascin-C predicts poor outcomes for patients with colorectal cancer and drives cancer stemness via Hedgehog signaling pathway

et al. 2020

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Background: Tenascin-C (TNC) is an extracellular matrix protein that is widely expressed in the stromal fibroblasts of various cancers. However, the roles of TNC in colorectal cancer (CRC) cells remain unclear. Methods: The expression of TNC, cancer stem cell-like (CSC) and cell cycle markers, and Hedgehog (HH) signaling pathway genes were assessed in 100 paraffin embedded clinical CRC patient tissues using immunohistochemistry. The interaction between TNC and CSC marker or HH related genes in CRC cells were detected by immunofluorescence. Cell cycle distribution was measured by flow cytometry. Migration and invasion were evaluated by transwell assays. The expressions of TNC, CSC marker, and HH related proteins were analyzed by western blot. Results: TNC expression was markedly upregulated in CRC tissues, and was associated with worse clinical outcomes. TNC overexpression was positively associated with CSC marker LSD1, cell cycle markers CDK4 and p16, and HH signaling pathway related genes SMO and GLI1 in clinical CRC tissue samples. TNC silencing downregulated the expression of the CSC marker LSD1, and the proliferation, migration, and invasion of CRC cells. Interestingly, the GLI1 inhibitor GANT61 strongly inhibited the expression of TNC in CRC cells. Conclusions: TNC may drive tumor progression and is involved in CSC properties via the HH signaling pathway. TNC has potential value in the evaluation of poor prognosis in CRC.

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“…Others have evaluated the predictive role of ubiquitin‐specific protease 22 (USP22) and found USP22 overexpression in approximately 50% of ESCC patients, which was associated with poorer 5‐year survival rates . Glioma‐associated oncogene homolog 1 (Gli1), CD44, and SOX9 expression have been linked to worse clinical outcome and poor prognosis of overall survival ( P = 0.005) and disease‐free survival ( P = 0.003) in ESCC . Testing of 328 ESCC and adjacent normal tissues showed that TRAP1‐positive patients had higher mortality and shorter overall survival, indicating that TRAP1 might be a protein predictive marker for poor prognosis, High ZBP‐89 expression in ESCC patients was correlated with shorter overall survival, compared with low ZBP‐89 expression level, and high expression of BRF2 protein was closely associated with tumor progression, angiogenesis, and poor survival of ESCC patients .…”

Section: Potential Protein Biomarkers For the Prognosis Of Esccmentioning

confidence: 99%

Tissue protein biomarker candidates to predict progression of esophageal squamous cell carcinoma and precancerous lesions

Wang

Smith

Wei

2018

Annals of the New York Academy of Sciences

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Esophageal squamous cell carcinoma (ESCC) is one of the most predominant malignancies worldwide. The 5-year survival rate is still relatively low due to few symptoms presenting with the early disease, diagnosis at middle to late stage, and high risk of recurrence after therapy. Novel protein biomarkers for early detection and treatment of ESCC have the potential to reduce incidence and mortality rates, and significantly prolong the 5-year survival rate. To date, several ESCC biomarkers are being investigated for screening, diagnosis, and treatment to decrease the disease burden. This review summarizes recent developments in candidate protein biomarkers for early diagnosis, predictors for precancerous disease progression, and prognosis of ESCC. Protein biomarkers that enable identification of the different pathologic grades of ESCC will need to be identified. ESCC biomarkers have the potential to improve screening and treatment strategies; multicenter prospective studies with large sample sizes will be required to confirm the usefulness of these candidate biomarkers.

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Gli1, a potential regulator of esophageal cancer stem cell, is identified as an independent adverse prognostic factor in esophageal squamous cell carcinoma

Abstract: Targeting Gli1, a potential diagnostic marker of ESCC stem cells, will have a profound therapeutic and prognostic value.

Cited by 42 publications

References 25 publications

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

Tenascin-C predicts poor outcomes for patients with colorectal cancer and drives cancer stemness via Hedgehog signaling pathway

Tissue protein biomarker candidates to predict progression of esophageal squamous cell carcinoma and precancerous lesions

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