Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Huang, Xin; Di, Xiao; Xu, Li; Zhong, Hongshan; Liao, Lian‐Di; Xie, Ze-Fen; Li, En‐Min

doi:10.3892/or_00000332

Cited by 14 publications

(6 citation statements)

References 22 publications

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“…In addition, its role in angiogenesis is supported by various data such as its high expression in the microvasculature of mouse glioma tumors (31), or its essential role in the sprouting of new blood vessels during zebrafish embryogenesis (34) and in many steps of human “ in vitro ” neovascularization (35). Interestingly, however, in the tumors analyzed in this work there was a good positive correlation between SDC2 levels and patient survival, data that has also been described in esophageal squamous cell carcinoma, prostate cancer, and pancreatic ductal adenocarcinoma, leading to the proposal that the expression levels of this molecule are of interest for diagnosis (36–38). These observations can be related to data suggesting a role for this PG as a metastasis inhibitor; thus a highly metastatic variant of Lewis lung carcinoma cells displays low SDC2 expression, and this molecule is able to suppress activation of matrix metalloproteinase-2 (39); Furthermore, it has been described that osteosarcoma cells that overexpress SDC2 are restricted in their migration and also exhibit enhanced apoptosis in vitro (40).…”

Section: Discussionsupporting

confidence: 57%

Neuroendocrine Tumors Show Altered Expression of Chondroitin Sulfate, Glypican 1, Glypican 5, and Syndecan 2 Depending on Their Differentiation Grade

et al. 2014

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Neuroendocrine tumors (NETs) are found throughout the body and are important as they give rise to distinct clinical syndromes. Glycosaminoglycans, in proteoglycan (PG) form or as free chains, play vital roles in every step of tumor progression. Analyzing tumor samples with different degrees of histological differentiation we determined the existence of important alterations in chondroitin sulfate (CS) chains. Analysis of the transcription of the genes responsible for the production of CS showed a decline in the expression of some genes in poorly differentiated compared to well-differentiated tumors. Using anti-CS antibodies, normal stroma was always negative whereas tumoral stroma always showed a positive staining, more intense in the highest grade carcinomas, while tumor cells were negative. Moreover, certain specific cell surface PGs experienced a drastic decrease in expression depending on tumor differentiation. Syndecan 2 levels were very low or undetectable in healthy tissues, increasing significantly in well-differentiated tumors, and decreasing in poorly differentiated NETs, and its expression levels showed a positive correlation with patient survival. Glypican 5 appeared overexpressed in high-grade tumors with epithelial differentiation, and not in those that displayed a neuroendocrine phenotype. In contrast, normal neuroendocrine cells were positive for glypican 1, displaying intense staining in cytoplasm and membrane. Low-grade NETs had increased expression of this PG, but this reduced as tumor grade increased, its expression correlating positively with patient survival. Whilst elevated glypican 1 expression has been documented in different tumors, the downregulation in high-grade tumors observed in this work suggests that this proteoglycan could be involved in cancer development in a more complex and context-dependent manner than previously thought.

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Section: Discussionsupporting

confidence: 57%

Neuroendocrine Tumors Show Altered Expression of Chondroitin Sulfate, Glypican 1, Glypican 5, and Syndecan 2 Depending on Their Differentiation Grade

et al. 2014

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“…Similarly, miR-9 was involved in suppression of inflammatory responses in atherosclerosis, wherein miR-9 inhibited the activation of the NLRP3 inflammasome, and thus attenuated atherosclerosisrelated inflammation through the JAK1/STAT signaling pathway (Wang et al, 2017). Moreover, the SDC2 gene plays a key role in the regulation of the TGF-β signaling pathway as a co-receptor for growth factors (Huang et al, 2009). Another study also documented the elevation of SDC2 during atherosclerotic plaque formation (Geeraert et al, 2007), suggesting that inhibition of SDC2 could suppress the process of atherosclerotic plaque formation, which is very much in line with our findings.…”

Section: Discussionmentioning

confidence: 99%

“…Web-available microarray analysis further indicated that Syndecan-2 (SDC2) is a potential target gene of miR-9. SDC2 is known to serve as a cell surface receptor which mediates adhesion-dependent signal transduction in the process of cell growth, migration, and differentiation (Huang et al, 2009). SDC2 has also been documented to exert particular effects on atherosclerotic plaque formation (Geeraert et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

microRNA-9 Inhibits Vulnerable Plaque Formation and Vascular Remodeling via Suppression of the SDC2-Dependent FAK/ERK Signaling Pathway in Mice With Atherosclerosis

et al. 2020

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microRNAs (miRNAs or miRs) play important roles in modulating the occurrence and progression of atherosclerosis and acute coronary syndrome (ACS). Herein, this study aimed to investigate the possible role of miR-9 in the development of atherosclerosis. Initially, the differentially expressed genes associated with ACS were screened and miRNAs that regulate syndecan-2 (SDC2) were predicted using microarray analysis. Furthermore, the biological functions of miR-9 and SDC2 on aortic plaque area, proliferation of collagen fibers, Mac-3-labeled macrophages, inflammatory response, and levels of the focal adhesion kinase/extracellular signal-regulated kinase (FAK/ERK) signaling pathway-related proteins in atherosclerosis were evaluated after ectopic miR-9 expression or SDC2 depletion in ACS mice using oil red O staining, Masson’s trichrome staining, immunohistochemistry, and Western blot analysis, respectively. SDC2 was highly-expressed, while miR-9 was poorly-expressed in atherosclerosis. Additionally, miR-9 targeted SDC2 and negatively-regulated its expression. Up-regulation of miR-9 reduced aortic plaque area, the proliferation of collagen fibers, Mac-3-labeled macrophages and levels of IL-6, IL-1β, and TNF-α by suppressing SDC2 and the FAK/ERK signaling pathway, thereby ameliorating atherosclerosis in ACS mice. In conclusion, the current study provides evidence that miR-9 retards atherosclerosis by repressing SDC2 and the FAK/ERK signaling pathway, highlighting a new theoretical basis for the treatment of atherosclerosis.

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“…37,61 Huang et al observed that the downregulation of SDC2 was associated with poor prognosis in esophageal squamous cell carcinoma. 62 Another study showed that SDC2 was hypermethylated in tumor tissue samples of gastric cancer patients compared with the corresponding non-tumor mucosa (CNM). 63 As the first step in our study, the SDC2 promoter was found to be strongly hypermethylated by pyrosequencing both in colonic adenoma and CRC samples compared with unmethylated healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Colorectal adenoma and cancer detection based on altered methylation pattern of SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples

et al. 2017

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Aberrant methylation is one of the most frequent epigenetic alterations that can contribute to tumor formation. Cell-free DNA can originate from tumor tissue; therefore, the evaluation of methylation markers in cell-free DNA can be a promising method for cancer screening. Our aim was to develop a panel of biomarkers with altered methylation along the colorectal adenoma-carcinoma sequence in both colonic tissue and plasma. Methylation of selected CpG sites in healthy colonic (n = 15), adenoma (n = 15), and colorectal cancer (n = 15) tissues was analyzed by pyrosequencing. MethyLight PCR was applied to study the DNA methylation of SFRP1, SFRP2, SDC2, and PRIMA1 gene promoters in 121 plasma and 32 biopsy samples. The effect of altered promoter methylation on protein expression was examined by immunohistochemistry. Significantly higher (P < 0.05) DNA methylation levels were detected in the promoter regions of all 4 markers, both in CRC and adenoma tissues compared with healthy controls. Methylation of SFRP1, SFRP2, SDC2, and PRIMA1 promoter sequences was observed in 85.1%, 72.3%, 89.4%, and 80.9% of plasma samples from patients with CRC and 89.2%, 83.8%, 81.1% and 70.3% from adenoma patients, respectively. When applied as a panel, CRC patients could be distinguished from controls with 91.5% sensitivity and 97.3% specificity [area under the curve (AUC) = 0.978], while adenoma samples could be differentiated with 89.2% sensitivity and 86.5% specificity (AUC = 0.937). Immunohistochemical analysis indicated decreasing protein levels of all 4 markers along the colorectal adenoma-carcinoma sequence. Our findings suggest that this methylation biomarker panel allows non-invasive detection of colorectal adenoma and cancer from plasma samples.

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Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Cited by 14 publications

References 22 publications

Neuroendocrine Tumors Show Altered Expression of Chondroitin Sulfate, Glypican 1, Glypican 5, and Syndecan 2 Depending on Their Differentiation Grade

Neuroendocrine Tumors Show Altered Expression of Chondroitin Sulfate, Glypican 1, Glypican 5, and Syndecan 2 Depending on Their Differentiation Grade

microRNA-9 Inhibits Vulnerable Plaque Formation and Vascular Remodeling via Suppression of the SDC2-Dependent FAK/ERK Signaling Pathway in Mice With Atherosclerosis

Colorectal adenoma and cancer detection based on altered methylation pattern of SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples

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