ANGPTL1 is a potential biomarker for differentiated thyroid cancer diagnosis and recurrence

Figures

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  Figure 1.. Low expression of ANGPTL1 is associated with thyroid tumor occurrence and development. (A) ANGPTL1 expression in thyroid cancer (n=501) and normal thyroid tissue (n=58; P<0.0001). Data were obtained from TCGA dataset. (B) ANGPTL1 expression levels were downregulated in thyroid cancer tissues compared with those in matched adjacent normal tissues in TCGA dataset. (C and D) ANGPTL1 expression levels were downregulated in thyroid cancer tissues compared with those of matched adjacent normal tissue in the GEO datasets (P=0.0006). (E) ANGPTL1 mRNA expression for different stages of thyroid cancer (P=0.0371). (F) Constituent ratio analysis of the level of ANGPTL1 for different stages of thyroid cancer (χ2=73.10, P<0.0001). ANGPTL1, angiopoietin-like protein 1; TCGA, The Cancer Genome Atlas; GEO, Gene Expression Omnibus.

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  Figure 2.. ANGPTL1 decreases thyroid cancer cell proliferation. (A) ANGPTL1 mRNA levels decreased with increasing DTC T stage. T1 group was significantly higher compared with T4 group. (B) Overexpression of ANGPTL1 in TPC-1 cells was verified by western blotting. ANGPTL1 overexpression significantly inhibited the proliferation of TPC-1 cells, which was determined by the CCK-8 assay. One-way ANOVA followed by Sidak's multiple comparisons test was used to determine statistical significance. (C) Knockdown of ANGPTL1 in TPC-1 cells was verified by western blotting. ANGPTL1 knockdown significantly enhanced the proliferation of TPC-1 cells as determined by the CCK-8 assay. One-way ANOVA followed by Sidak's multiple comparisons test was used to determine statistical significance. (D) Gene signatures for ‘positive regulation of epithelial cell proliferation’ (FDR=0.008) and ‘regulation of cell proliferation’ (FDR=0.000) were enriched in the low ANGPTL1expression group. ANGPTL1, angiopoietin-like protein 1; CCK8, Cell Counting Kit 8; si, small interfering RNA; NC, negative control; HA, hemagglutinin tag; FDR, false discovery rate; GO, Gene Ontology; TCGA, The Cancer Genome Atlas.

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  Figure 3.. ANGPTL1 inhibits DTC cell migration and invasion. (A) Expression levels of ANGPTL1 were significantly higher in patients with N0 stage thyroid cancer compared with those in patients with N1 stage thyroid cancer (P<0.0001). (B) ANGPTL1 overexpression inhibited cell migration as demonstrated by the wound healing assay. The relative migration distance was quantified (bottom panel; P=0.0024) (C) ANGPTL1 overexpression inhibited cell invasion as demonstrated by the Transwell invasion assay (P=0.0014). (D) Gene signatures for ‘positive regulation of epithelial cell migration’ (FDR=0.016) and ‘cell migration’ (FDR=0.004) were enriched within the low ANGPTL1 expression group. (E) Gene signatures for ‘Multicancer invasiveness signature’ (FDR=0.000) were enriched within the low ANGPTL1 expression group. ANGPTL1, angiopoietin-like protein 1; TCGA, The Cancer Genome Atlas; HA, hemagglutinin tag; FDR, false discovery rate.

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  Figure 4.. Low ANGPTL1 expression is associated with DTC recurrence. (A) ANGPTL1 expression in patients with DTC with or without recurrence from TCGA database. (B and C) Gene signatures for (B) ‘MAPK signaling pathway’ (FDR=0.012) and (C) ‘AKT pathway’ were enriched in the low ANGPTL1 expression group. ANGPTL1, angiopoietin-like protein 1; TCGA, The Cancer Genome Atlas; MAPK, mitogen-activated protein kinase; KEGG, Kyoto Encyclopedia of Genes and Genomes; FDR, false discovery rate.

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  Figure 5.. Serum ANGPTL1 is a potential biomarker for thyroid cancer diagnosis. (A) Serum ANGPTL1 levels in patients with DTC and benign thyroid nodules. (B) Receiver operating characteristic curve for ANGPTL1 serum levels as a diagnostic criterion for thyroid cancer. ANGPTL1, angiopoietin-like protein 1; AUC, area under the curve.