Syndecan-2 in colorectal cancer plays oncogenic role via epithelial-mesenchymal transition and MAPK pathway

Hua, Ruheng; Yu, Jiang; Yan, Xiaohui; Ni, Qingfeng; Zhi, Xiaofei; Li, Xiaolong; Ji, Bin; Jun, Zhu

doi:10.1016/j.biopha.2019.109630

“…Syndecan-2 protein, encoded by the SDC2 gene, is a type I transmembrane proteoglycan. The role of SDC2 depends on the type of tumor: it acts as an oncogene and contributes to disease progression in colon cancer, breast cancer and melanoma, while it serves as a metastasis suppressor in Lewis lung carcinoma [39][40][41]. Moreover, SDC2 has been found to be positively associated with the differentiation level and prognosis of neuroendocrine tumors, which is consistent with our ndings [42].…”

Section: Disscussionsupporting

confidence: 89%

Identification of an Immune-related Signature That Indicates the Dedifferentiation of Thyroid Cells

Wang

¹

,

Li

²

,

Qin

³

et al. 2020

Preprint

0

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Background: Patients with well-differentiated thyroid carcinoma can achieve long-term survival after reasonable treatments, but there is no standard treatment mode for poorly or undifferentiated thyroid carcinoma and its prognosis is very poor. Immune cells, especially tumor-associated macrophages, account for a large proportion of the tumor microenvironment of anaplastic thyroid carcinomas (ATCs). However, whether immune-related genes can mediate the dedifferentiation of thyroid cells is unclear.Methods: We initially compared the differences of thyroid differentiation score, infitration of immune cells and enriched pathways between ATCs and papillary thyroid carcionma (PTCs) or normal thyroid tissues in Gene Expression Omnibus database. Then, The Cancer Genome Atlas database was used to screen out the prognosis associated IRGs. A risk score was constructed and we next investigated its predictive value for differentiation by applying receiver operating characteristic (ROC) curves and correlation analyses. Kaplan-Meier curves were used to evaluated its prognostic value. We further explored the associations of the risk score with important immune checkpoint molecules, infiltrating immune cells and response to immunotherapy.Results: Compared with PTCs or normal thyroid tissues, ATCs exhibited lower thyroid differentiation scores, higher infiltration of most immune cells and higher activation of inflammatory response. The risk score composed of MMP9 and SDC2 was significantly increased in ATCs and low differentiated PTCs. Moreover, it showed favorable predictive value for differentiation and survival. Higher risk score displayed dedifferentiation status and a worse prognosis. Additionly, the risk score was positively correlated with immune checkpoint molecules PDL1, CTLA4, IDO1, HAVCR2 and infiltration of multiple immune cells. Importantly, we found that samples with higher risk score tend to have a better response to immune checkpoint agents than lower ones.Conclusion: Our findings indicate that the risk score may not only contribute to the judgement of differentiation and prognosis of thyroid cancer, but also help to the prediction of immune cell infiltration and immune checkpoint inhibitor response.

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“…In spite of this, the study of SV2B in tumors is still limited. Relatively speaking, SDC2 has been well studied in various tumors, especially in colorectal cancer, lung cancer, prostate cancer, and esophageal squamous cell carcinoma [ 41 – 45 ]. According to the discussion above, we considered that SV2B and SDC2 deserved to be further studied in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Progressive and Prognostic Performance of an Extracellular Matrix-Receptor Interaction Signature in Gastric Cancer

Yang

¹

,

Chen

²

,

Mao

³

et al. 2020

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The role of an extracellular matrix- (ECM-) receptor interaction signature has not been fully clarified in gastric cancer. This study performed comprehensive analyses on the differentially expressed ECM-related genes, clinicopathologic features, and prognostic application in gastric cancer. The differentially expressed genes between tumorous and matched normal tissues in The Cancer Genome Atlas (TCGA) and validation cohorts were identified by a paired t -test. Consensus clusters were built to find the correlation between clinicopathologic features and subclusters. Then, the least absolute shrinkage and selection operator (lasso) method was used to construct a risk score model. Correlation analyses were made to reveal the relation between risk score-stratified subgroups and clinicopathologic features or significant signatures. In TCGA (26 pairs) and validation cohort (134 pairs), 25 ECM-related genes were significantly highly expressed and 11 genes were downexpressed in gastric cancer. ECM-based subclusters were slightly related to clinicopathologic features. We constructed a risk score model = 0.081 ∗ log 2 CD 36 + 0.043 ∗ log 2 COL 5 A 2 + 0.001 ∗ log 2 ITGB 5 + 0.039 ∗ log 2 SDC 2 + 0.135 ∗ log 2 SV 2 B + 0.012 ∗ log 2 THBS 1 + 0.068 ∗ log 2 VTN + 0.023 ∗ log 2 VWF . The risk score model could well predict the outcome of patients with gastric cancer in both training ( n = 351 , HR: 1.807, 95% CI: 1.292-2.528, P = 0.00046 ) and validation ( n = 300 , HR: 1.866, 95% CI: 1.347-2.584, P = 0.00014 ) cohorts. Besides, risk score-based subgroups were associated with angiogenesis, cell adhesion molecules, complement and coagulation cascades, TGF-beta signaling, and mismatch repair-relevant signatures ( P < 0.0001 ). By univariate (1.845, 95% CI: 1.382-2.462, P < 0.001 ) and multivariate (1.756, 95% CI: 1.284-2.402, P < 0.001 ) analyses, we regarded the risk score as an independent risk factor in gastric cancer. Our findings revealed that ECM compositions became accomplices in the tumorigenesis, progression, and poor survival of gastric cancer.

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“…Conversely, reduced expression of SDC1 has been found in mesothelioma, non-small-cell lung cancer, prostate cancer, and sarcoma [35,108,110,111]. SDC2 expression is upregulated in breast, colon, and pancreatic cancers, and melanomas, whereas high levels of SDC2 in neuroendocrine tumors correlate with a better survival of patients [112,113]. On the contrary, a tumor-suppressor function for SDC2 correlated to apoptosis dysregulation in osteosarcoma has been suggested [114].…”

Section: Collagen Type VIII Col8a1mentioning

confidence: 99%

“…However, a significant reduction of cell surface tethered SDC1 and an increase of shed SDC1 in the ECM has been observed as a function of tumor progression and aggressiveness, suggesting the involvement of post-transcriptional mechanisms in SDC1 expression in this type of tumor. Differential regulation of SDC1 expression as well as of the other SDC isoforms, GPCs, and the other HSPGs has been found in several tumors ( Table 3 ) [ 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ].…”

Section: Structural Features Biosynthesis and Enzymatic Modificamentioning

confidence: 99%

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Pasquale

¹

,

Pavone

²

2020

IJMS

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In the last few decades, heparan sulfate (HS) proteoglycans (HSPGs) have been an intriguing subject of study for their complex structural characteristics, their finely regulated biosynthetic machinery, and the wide range of functions they perform in living organisms from development to adulthood. From these studies, key roles of HSPGs in tumor initiation and progression have emerged, so that they are currently being explored as potential biomarkers and therapeutic targets for cancers. The multifaceted nature of HSPG structure/activity translates in their capacity to act either as inhibitors or promoters of tumor growth and invasion depending on the tumor type. Deregulation of HSPGs resulting in malignancy may be due to either their abnormal expression levels or changes in their structure and functions as a result of the altered activity of their biosynthetic or remodeling enzymes. Indeed, in the tumor microenvironment, HSPGs undergo structural alterations, through the shedding of proteoglycan ectodomain from the cell surface or the fragmentation and/or desulfation of HS chains, affecting HSPG function with significant impact on the molecular interactions between cancer cells and their microenvironment, and tumor cell behavior. Here, we overview the structural and functional features of HSPGs and their signaling in the tumor environment which contributes to tumorigenesis and cancer progression.

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Syndecan-2 in colorectal cancer plays oncogenic role via epithelial-mesenchymal transition and MAPK pathway

Cited by 49 publications

References 44 publications

Identification of an Immune-related Signature That Indicates the Dedifferentiation of Thyroid Cells

Identification of an Immune-related Signature That Indicates the Dedifferentiation of Thyroid Cells

Progressive and Prognostic Performance of an Extracellular Matrix-Receptor Interaction Signature in Gastric Cancer

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

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