Circulating Levels of GDF15, MMP7 and miR-200c as a Poor Prognostic Signature in Gastric Cancer

Blanco-Calvo, Moisés; Tarrío, Nuria; Reboredo, Margarita; Haz-Conde, Mar; García, J. Suárez; Quindós, María; Figueroa, Angélica; Antón-Aparicio, Luis; Calvo, Lourdes; Valladares‐Ayerbes, Manuel

doi:10.2217/fon.13.263

Cited by 37 publications

(42 citation statements)

References 66 publications

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“…In colorectal cancer, patients with high plasma levels showed shorter time to recurrence and reduced overall survival (OS) subsequent to serum sampling (Wallin et al, 2011). The association between high sGDF-15 and poor outcome was further shown for thyroid, pancreatic, gastric, ovarian, and other cancers (Bauskin et al, 2006;Blanco-Calvo et al, 2014;Brown et al, 2009;Mimeault and Batra, 2010;Staff et al, 2010). Similar findings have also been reported for the level of GDF-15 tissue expression as assessed by immunohistochemistry (Wallin et al, 2011).…”

Section: Introductionsupporting

confidence: 56%

High GDF-15 Serum Levels Independently Correlate with Poorer Overall Survival of Patients with Tumor-Free Stage III and Unresectable Stage IV Melanoma

Weide

Schäfer

Martens

et al. 2016

Journal of Investigative Dermatology

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Biomarkers are strongly needed for diagnostic surveillance of patients with metastatic melanoma. On the basis of its known association with tumor metastasis and its ability to induce cancer cachexia, we investigated serum levels of growth and differentiation factor 15 (sGDF-15) as a marker for overall survival (OS). sGDF-15 was retrospectively measured by ELISA in 761 samples obtained at distinct time points during routine clinical care of patients with stage III/IV melanoma. In the entire cohort, sGDF-15 ≥ 1.5 ng/ml was strongly associated with reduced OS after assessment. Subsequent analyses were performed separately for tumor-free stage III, tumor-free stage IV, and unresectable stage IV patients. For patients with unresectable distant metastasis (n = 206), sGDF-15 was independently associated with OS when considered together with the M-category and superior to serum level of lactate dehydrogenase. Analysis in tumor-free stage III patients during routine surveillance (n = 468) revealed sGDF-15 to be associated with OS and an independent factor when considered together with S100B and the pattern of locoregional metastasis. Only in tumor-free stage IV patients (n = 87) sGDF-15 was not associated with OS. sGDF-15 should thus be further validated as a marker for early detection of recurrence in stage III patients and as a prognostic or predictive marker particularly in the context newly available treatments in unresectable stage IV patients.

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Section: Introductionsupporting

confidence: 56%

High GDF-15 Serum Levels Independently Correlate with Poorer Overall Survival of Patients with Tumor-Free Stage III and Unresectable Stage IV Melanoma

Weide

Schäfer

Martens

et al. 2016

Journal of Investigative Dermatology

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“…However, a poor overlap exists between these biomarkers of GC. Thus, it might be a better resolution to establish more accurate prognostic gene signatures using a combination of different types of transcripts . A growing volume of literature has demonstrated that ncRNAs, predominantly miRNAs, could serve as potential biomarkers of GBC .…”

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNA linc00261 suppresses gastric cancer progression via promoting Slug degradation

Zhang

et al. 2016

J Cellular Molecular Medi

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Gastric cancer (GC) remains a threat to public health with high incidence and mortality worldwide. Increasing evidence demonstrates that long non‐coding RNAs (lncRNAs) play critical regulatory roles in cancer biology, including GC. Previous profiling study showed that lncRNA linc00261 was aberrantly expressed in GC. However, the role of linc00261 in GC progression and the precise molecular mechanism remain unknown. In this study, we report that linc00261 was significantly down‐regulated in GC tissues and the expression level of linc00261 negatively correlated with advanced tumour status and clinical stage as well as poor prognostic outcome. In vitro functional assays indicate that ectopic expression of linc00261 suppressed cell invasion by inhibiting the epithelial–mesenchymal transition (EMT). By RNA pull‐down and mass spectrum experiments, we identified Slug as an RNA‐binding protein that binds to linc00261. We confirmed that linc00261 down‐regulated Slug by decreasing the stability of Slug proteins and that the tumour‐suppressive function of linc00261 can be neutralized by Slug. linc00261 may promote the degradation of Slug via enhancing the interaction between GSK3β and Slug. Moreover, linc00216 overexpression repressed lung metastasis in vivo. Together, our findings suggest that linc00261 acts a tumour suppressor in GC by decreasing the stability of Slug proteins and suppressing EMT. By clarifying the mechanisms underlying GC progression, these findings may facilitate the development of novel therapeutic strategies for GC.

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“…According to the inclusion criteria, seven GEO datasets (, , , , , , ) and four suitable literature sources were finally included.…”

Section: Methodsmentioning

confidence: 99%

“…According to the inclusion criteria, seven GEO datasets (GSE2685, GSE13911, GSE19826, GSE79973, GSE29272, GSE54129, GSE38932) and four suitable literature sources [11,20,25,26] were finally included.…”

Section: Search Strategy and Inclusion Criteriamentioning

confidence: 99%

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Utility of GDF‐15 as a diagnostic biomarker in gastric cancer: an investigation combining GEO, TCGA and meta‐analysis

Liu

Dong

et al. 2018

FEBS Open Bio

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It was recently suggested that growth differentiation factor‐15 ( GDF ‐15) is associated with gastric cancer ( GC ) carcinogenesis. However, the diagnostic potential of GDF ‐15 for GC remains unclear. To address this issue, we obtained RNA sequencing and microarray data from the Gene Expression Omnibus ( GEO ) and The Cancer Genome Atlas ( TCGA ) databases, and searched PubMed, Google Scholar and Web of Science for relevant literature. We then used STATA to perform a meta‐analysis. In total, reports of 253 GC patients and 112 healthy controls who contributed peripheral blood samples were taken from the four literature sources, while information on 754 GC tumor and 263 gastric normal tissues was drawn from TCGA and seven GEO datasets. The expression level of GDF ‐15 mRNA was significantly higher in tumor tissues than in normal tissues, with a standard mean difference ( SMD ) of 0.79% and a 95% confidence interval (95% CI ) of 0.63–0.95. Consistently, the GDF ‐15 protein in blood was significantly increased in GC patients as compared to controls ( SMD = 3.74, 95% CI = 1.81–5.68). In addition, based on information from TCGA and GEO datasets, the expression level of GDF ‐15 mRNA may be of use for the diagnosis of GC , with a combined sensitivity, specificity and odds ratio of 0.69 (95% CI = 0.58–0.79), 0.90 (95% CI = 0.84–0.93) and 6.32 (95% CI = 4.22–9.49), respectively. The summary receiver operating characteristic curve demonstrated that the area under the curve was 0.90 (95% CI = 0.87–0.93). The results suggest higher levels of GDF ‐15 may be associated with GC tumorigenesis and may have the potential to be a diagnostic biomarker of GC.

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Circulating Levels of GDF15, MMP7 and miR-200c as a Poor Prognostic Signature in Gastric Cancer

Abstract: GDF15 and MMP7 serum levels have diagnostic value for GC. The combination marker formed by GDF15, MMP7 and miR-200c is indicative of adverse evolution in GC patients.

Cited by 37 publications

References 66 publications

High GDF-15 Serum Levels Independently Correlate with Poorer Overall Survival of Patients with Tumor-Free Stage III and Unresectable Stage IV Melanoma

High GDF-15 Serum Levels Independently Correlate with Poorer Overall Survival of Patients with Tumor-Free Stage III and Unresectable Stage IV Melanoma

Long non‐coding RNA linc00261 suppresses gastric cancer progression via promoting Slug degradation

Utility of GDF‐15 as a diagnostic biomarker in gastric cancer: an investigation combining GEO, TCGA and meta‐analysis

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