Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer

Sun, Ruochuan; Wu, Jing; Chen, Yuanyuan; Lu, Mingdian; Zhang, Shangxin; Lu, Daru; Li, Yongxiang

doi:10.1186/1476-4598-13-225

Cited by 67 publications

(65 citation statements)

References 40 publications

(39 reference statements)

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“…We also proposed THBS2 as a prognostic indicator of gastric cancer, with high THBS2 expression related to poor prognosis. However, Sun et al reported that aberrant expression of THBS2 could be a potential predictor of gastric cancer prognosis, i.e., the downregulation of THBS2 indicated poor prognosis [20]. While Sun et al used 14 pairs of gastric tumor tissues and adjacent normal tissues in their study, we used a larger number of tissues, which makes our results more convincing.…”

mentioning

confidence: 78%

Elevated THBS2, COL1A2, and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis

Zhuo

Zhuang

et al. 2016

Cell Physiol Biochem

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Background/Aims:Gastric cancer (GC) is an important health problem. Classification based on molecular subtypes may help to determine the prognosis of patients with GC. Tumor invasion and metastasis are important factors affecting the prognosis of cancer. We aimed to identify genes related to tumor invasion and metastasis, which may serve as indicators of good GC prognosis. Methods:Tumor tissues and adjacent normal tissues were collected from 105 patients with primary GC who were treated by undergoing radical surgery. Samples were used for tissue microarray analysis. Identified genes with altered expression were further analyzed using the Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The expression levels of THBS2, COL1A2 and SPP1 were analyzed by RT-PCR, western blot and immunohistochemistry. The overall survival curves of patients with high and low expression of each gene of interest were plotted and compared. Results:Forty-three genes were identified. THBS2, COL1A2 and SPP1 were selected for further analysis. Altered expression levels of THBS2, COL1A2 and SPP1 in tumor tissues were confirmed. Patients with low THBS2 expression had a better prognosis; the expression of COL1A2 and SPP1 might not affect the prognosis of patients with GC. Conclusion:THBS2, but not COL1A2 and SPP1, may serve as an indicator of GC prognosis.

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confidence: 78%

Elevated THBS2, COL1A2, and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis

Zhuo

Zhuang

et al. 2016

Cell Physiol Biochem

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“…Previous studies have reported that low expression levels of THBS2 are associated with poor prognoses in gastric cancer, 34 prostate cancer, 35 colon cancer 36 and pancreatic cancer. 37 Moreover, THBS2 contributes to cancer progression, such as invasion 37 and metastasis.…”

Section: Discussionmentioning

confidence: 99%

miR-135b, a key regulator of malignancy, is linked to poor prognosis in human myxoid liposarcoma

Nezu

Hagiwara²,

Yamamoto³

et al. 2016

Oncogene

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Myxoid/round cell (RC) liposarcomas (MLS) were originally classified into two distinct populations based on histological differences; a myxoid component and a RC component. It is notable that, depending on an increase of the RC component, the prognosis significantly differs. Hence, the RC component is associated with metastasis and poor prognosis. However, the molecular mechanisms that contribute to the malignancy of the RC component still remain largely unknown. Here, we report microRNA-135b (miR-135b), a key regulator of the malignancy, highly expressed in the RC component and promoting MLS cell invasion in vitro and metastasis in vivo through the direct suppression of thrombospondin 2 (THBS2). Decreased THBS2 expression by miR-135b increases the total amount of matrix metalloproteinase 2 (MMP2) and influences cellular density and an extracellular matrix structure, thereby resulting in morphological change in tumor. The expression levels of miR-135b and THBS2 significantly correlated with a poor prognosis in MLS patients. Overall, our study reveals that the miR-135b/THBS2/MMP2 axis is tightly related to MLS pathophysiology and has an important clinical implication. This work provides noteworthy evidence for overcoming metastasis and improving patient outcomes, and sheds light on miR-135b and THBS2 as novel molecular targets for diagnosis and therapy in MLS.

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“…We found that THBS2 antigen is robustly expressed in PDAC tumor tissue, perhaps concordant with the poor vascularization associated with PDAC, and is also increased in plasma of PDAC patients. Interestingly, THBS2 is downregulated in gastric cancer cells (44). Further work is needed to understand how the release of THBS2 into plasma is increased in the patients cohorts studied here.…”

Section: Discussionmentioning

confidence: 99%

Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19-9 blood markers

et al. 2017

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Markers are needed to facilitate early detection of pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed too late for effective therapy. Starting with a PDAC cell reprogramming model that recapitulated the progression of human PDAC, we identified secreted proteins and tested and validated a subset of them as potential markers of PDAC. We optimized an ELISA assay using plasma samples from patients with various stages of PDAC, from individuals with benign pancreatic disease, and from healthy controls. Clinical studies including a phase 1 discovery study (N=20 patients), a phase 2a validation study (N=189), and a second phase 2b validation study (N=537) revealed that concentrations of plasma thrombospondin-2 (THBS2) discriminated among all stages of PDAC consistently over the three studies with a Receiver Operating Characteristic (ROC) c-statistic of 0.76 in Phase 1, 0.842 in Phase 2a, and 0.875 in Phase 2b. The concentration of THBS2 in plasma performed as well at discriminating resectable stage I cancer as stage III/IV PDAC. THBS2 concentrations combined with those for CA19-9, a previously identified PDAC marker, yielded a c-statistic of 0.956 in the Phase 2a study and 0.970 in the Phase 2b study. THBS2 data improved the ability of CA19-9 to distinguish PDAC from pancreatitis. With a specificity of 98%, the combination of THBS2 and CA19-9 yielded a sensitivity of 87% for PDAC in the Phase 2b study. Given this, a THBS2 and CA19-9 panel assessed in human blood using a conventional ELISA assay may improve the detection of patients at high risk for PDAC.

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Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer

Cited by 67 publications

References 40 publications

Elevated THBS2, COL1A2, and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis

Elevated THBS2, COL1A2, and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis

miR-135b, a key regulator of malignancy, is linked to poor prognosis in human myxoid liposarcoma

Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19-9 blood markers

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