Reduced expression of SMAD4 in gliomas correlates with progression and survival of patients

He, Shiming; Zhao, Zhenwei; Wang, Yuan; Zhao, Ji-pei; Wang, Liang; Hou, Fang; Gao, Guodong

doi:10.1186/1756-9966-30-70

Cited by 27 publications

(20 citation statements)

References 16 publications

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“…Further, a recent study demonstrated that decreased levels of both SMAD4 mRNA and protein in glioma compared to normal (P < 0.001). There was a gradual decrease in SMAD4 expression levels from grade I to grade IV glioma [22]. The survival rate of SMAD4-positive patients was higher than that of SMAD4-negative patients and demonstrated that the loss of SMAD4 was a significant and independent prognostic indicator in glioma.…”

Section: Discussionmentioning

confidence: 91%

Prognostic implication of the loss of TGFBR2 expression in oral carcinoma

Sivadas¹,

Saakshi²,

Iype³

et al. 2015

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Oral squamous cell carcinoma (OSCC) is a disease that strikes many worldwide, accounting for more than 145,000 deaths annually. This study examined the role of Transforming Growth Factor Beta (TGFβ) signalling alterations in oral carcinogenesis and also its influence on the disease prognosis. In presented study, we evaluated the protein-level alterations of core TGFβ signalling members in 20 potentially malignant oral disorders (PMDs) - leukoplakia and submucous fibrosis and 87 oral cancer samples by western blotting. Further, we analysed the association between these alterations and prognosis of oral carcinoma. For statistical analyses, univariate test like Student's 't'-test to compare expression level of various genes and logrank test has been used to compare the Kaplan-Meier survival curves. The multivariate model such as Cox's proportional hazard regression was used to verify the independent influence of each variable on the survival endpoints. A gradual decrease in the expression of TGFβ signalling members like SMAD2, SMAD4, TGFBR1 and TGFBR2 have been noted from normal to PMD in oral cancers. The bio-activeforms, SMAD2/3 also showed a similar trend. SMAD3 protein was downregulated significantly in the PMD stage itself. Thus an inverse correlation was observed between expression of TGFβ members and oral cancer progression.Furthermore, oral cancer patients showing TGFBR2 downregulation exhibited poor disease-free survival (p=0.005) and poor overall survival (p=0.012).Thus, assessing the TGFBR2 protein levels can serve as one of the prognostic marker for oral cancer.

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Section: Discussionmentioning

confidence: 91%

Prognostic implication of the loss of TGFBR2 expression in oral carcinoma

Sivadas¹,

Saakshi²,

Iype³

et al. 2015

neo

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“…Here, we demonstrated that M146-exo decreased EGFR and NF-κB protein in 9L glioma cells in vitro . miR-146b has also been identified to inhibit SMAD4, the loss of which is a independent indicator of poor outcome in glioma [7, 10]. Therefore, it is likely that concurrent inhibition of factors in addition to EGFR underpins the anti-tumor effect of M146-exo.…”

Section: Discussionmentioning

confidence: 99%

Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth

et al. 2013

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Exosomes are 30–150 nm vesicles secreted by a wide range of mammalian cells that can contain microRNA (miRNA). To test if marrow stromal cell (MSC) exosomes could be used as a vehicle for delivery of anti-tumor miRNAs, we transfected MSCs with a miR-146b expression plasmid, and harvested exosomes released by the MSCs. Intra-tumor injection of exosomes derived from miR-146-expressing MSCs significantly reduced glioma xenograft growth in a rat model of primary brain tumor.

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“…Previous studies demonstrated that SMAD4 was considered as a tumor suppressor and was frequently mutated or homozygously deleted in pancreatic cancer and colorectal cancer [11], [12], [13]. Loss expression of SMAD4 was associated with poor clinical outcomes in patients with pancreatic, colon, and brain cancers[14], [15], [16]. Although mutation and homozygous deletion of SMAD4 were rare in head and neck squamous cell carcinoma (HNSCC)[17], knockout SMAD4 could lead to spontaneous oral squamous cell carcinoma development in an animal model[18], suggesting the tumor suppressor role of SMAD4 in oral tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

The Combination of SMAD4 Expression and Histological Grade of Dysplasia Is a Better Predictor for the Malignant Transformation of Oral Leukoplakia

et al. 2013

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Oral leukoplakia (OL) is the most common premalignancy in the oral cavity and can progress to oral squamous cell carcinoma (OSCC). SMAD4 is a tumor suppressor implicated in multiple cancer types including OSCC. To assess the role of SMAD4 in oral leukoplakia malignant transformation, the authors investigated SMAD4 expression patterns in OL and OSCC using a highly specific antibody and correlated the patterns with the risk of malignant transformation oral leukoplakia. Immunohistochemistry and a quantitative imaging system were used to measure SMAD4 expression in OL from 88 OL patients, including 22 who later went through malignant transformation, and their OSCC counterpart. Forty-three (48.9%) of the 88 OL patients had strong SMAD4 expression. SMAD4 expression had no significant correlation with patients' clinicopathological parameters. Interestingly, 17 (39.5%) of the 43 OL lesions with strong SMAD4 expression went through malignant transformation whereas only 5 (11.1%) of the 45 OL lesions with weak SMAD4 expression did so (p = 0.002). The SMAD4 expression in OL was much higher than that in their OSCC counterpart. Kaplan-Meier analysis revealed that the combination of SMAD4 expression and histological grade of dysplasia (p = 0.007) is a better predictor for the malignant transformation of oral leukoplakia. In the multivariate analysis, both SMAD4 expression and grade of dysplasia were identified as independent factors for OL malignant transformation risk (p = 0.013 and 0.021, respectively). It was concluded that high SMAD4 expression may be indicative of an early carcinogenic process in OL and serve as an independent biomarker in assessing malignant transformation risk in patients with OL, and the combination of SMAD4 expression and histological grade of dysplasia is a better predictor for the malignant transformation of oral leukoplakia.

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Reduced expression of SMAD4 in gliomas correlates with progression and survival of patients

Cited by 27 publications

References 16 publications

Prognostic implication of the loss of TGFBR2 expression in oral carcinoma

Prognostic implication of the loss of TGFBR2 expression in oral carcinoma

Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth

The Combination of SMAD4 Expression and Histological Grade of Dysplasia Is a Better Predictor for the Malignant Transformation of Oral Leukoplakia

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