A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer

Low, Yee Syuen; Blöcker, Christopher; McPherson, John R.; Tang, See Aik; Cheng, Ying; Wong, Joyner Y.S.; Chua, Clarinda; Lim, Tony Kiat Hon; Tang, Choong Leong; Chew, Min Hoe; Tan, Patrick; Tan, Iain Beehuat; Rozen, Steven G.; Cheah, Peh Yean

doi:10.1016/j.canlet.2017.05.031

Cited by 16 publications

(17 citation statements)

References 30 publications

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“…2A). Furthermore, the inverse relationship between PD-L1 and miR-148a-3p expression was confirmed in an additional mRNA/miRNA microarray dataset of pMMR colorectal cancer by Low and colleagues (24), in which miR-148a-3p was significantly decreased in PD-L1 High tumors (P ¼ 0.0073; Fig. 2B).…”

Section: Association Between Mir-148a-3p Pd-l1 and Mmr Statussupporting

confidence: 52%

“…We utilized microarray gene expression and miRNA expression profiles from 148 patients with MSS colorectal cancer (24). These datasets are publicly available from the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo), deposited as GSE81980 on the basis of Affymetrix Human Genome U133 Plus 2.0 array, and GSE81981 based on Agilent-070156 Human miRNA array.…”

Section: Microarray Data Analysismentioning

confidence: 99%

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miRNA-148a-3p Regulates Immunosuppression in DNA Mismatch Repair–Deficient Colorectal Cancer by Targeting PD-L1

Ashizawa

Okayama

Ishigame

et al. 2019

Molecular Cancer Research

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Immunotherapy against the interaction between programmed cell death 1/programmed cell death ligand 1 (PD-L1) has emerged as a promising strategy for colorectal cancer with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). The study aimed to identify miRNAs that posttranscriptionally control PD-L1 expression on tumor cells and also regulate immune evasion. A comprehensive miRNA screening using The Cancer Genome Atlas (TCGA) dataset (n ¼ 260) combined with eight different miRNA target prediction programs resulted in the identification of a tumor suppressive miRNA, miR-148a-3p, as a potential negative regulator of PD-L1 expression, particularly in dMMR/MSI-H colorectal cancer. Using multiple cohorts of colorectal cancer, including TCGA data, a microarray dataset (n ¼ 148), and formalin-fixed, paraffin-embedded samples (n ¼ 395), we found that the expression of miR-148a-3p was decreased in dMMR/MSI-H tumors, correlating inversely with PD-L1 levels. We demonstrate that miR-148a-3p directly binds to the 3 0 -untranslated region of PD-L1, thereby reducing whole-cell and cell surface PD-L1 levels in HCT116 and SW837 cell lines. Overexpression of miR-148a-3p repressed IFNg-induced PD-L1 expression on tumor cells and consequently diminished T-cell apoptosis in a coculture model of IL2-activated T cells and IFNg-treated tumor cells. In conclusion, our data support a regulatory mechanism of PD-L1 expression on tumor cells and immune suppression via miR-148a-3p downregulation in colorectal cancer. Implications:This study provides novel evidence that miR-148a-3p negatively regulates tumor cell PD-L1 expression and decreased levels of miR-148a-3p contributes to the immunosuppressive tumor microenvironment.

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Section: Association Between Mir-148a-3p Pd-l1 and Mmr Statussupporting

confidence: 52%

Section: Microarray Data Analysismentioning

confidence: 99%

miRNA-148a-3p Regulates Immunosuppression in DNA Mismatch Repair–Deficient Colorectal Cancer by Targeting PD-L1

Ashizawa

Okayama

Ishigame

et al. 2019

Molecular Cancer Research

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“…Machine learning methods based on predictive (classification) models using RF have recently been widely applied in many diagnostic, prognostic and therapeutic studies (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Machine learning methods based on predictive (classification) models using RF have recently been widely applied in many diagnostic, prognostic and therapeutic studies (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

“…Our study provides evidence for the clinical benefits of quantitative immunophenotyping by a rational and effective marker panel followed by the use of a predictive model (diagnostic classifier), minimizing the subjectivity of commonly used expert-based assessment. Machine learning methods based on predictive (classification) models using RF have recently been widely applied in many diagnostic, prognostic and therapeutic studies (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Hereby we also showed its utility for the evaluation of flow cytometry data.…”

Section: Discussionmentioning

confidence: 99%

Quantitative assessment of informative immunophenotypic markers increases the diagnostic value of immunophenotyping in mature CD5‐positive B‐cell neoplasms

Starostka

Kriegová

Kudělka

et al. 2018

Cytometry Part B Clinical

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“…Tumor metastasis is the main cause of poor prognosis of CRC, thus, early predictive diagnosis of highly metastatic CRC will be helpful for the clinical treatment of patients [30,31]. In our study, we have demonstrated that GFRA1 hypomethylation accompanied with upregulation of GFRA1 in invasive CRC, and correlated with poor prognosis of patients.…”

Section: Discussionmentioning

confidence: 51%

Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer

et al. 2020

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Tumor metastasis is the major cause of poor prognosis and mortality in colorectal cancer (CRC). However, early diagnosis of highly metastatic CRC is currently difficult. In the present study, we screened for a novel biomarker, GDNF family receptor alpha 1 (GFRA1) based on the expression and methylation data in CRC patients from The Cancer Genome Altlas (TCGA), followed by further analysis of the correlation between the GFRA1 expression, methylation, and prognosis of patients. Our results show DNA hypomethylation-mediated upregulation of GFRA1 in invasive CRC, and it was found to be correlated with poor prognosis of CRC patients. Furthermore, GFRA1 methylation-modified sequences were found to have potential as methylation diagnostic markers of highly metastatic CRC. The targeted demethylation of GFRA1 by dCas9-TET1CD and gRNA promoted CRC metastasis in vivo and in vitro. Mechanistically, demethylation of GFRA1 induces epithelial-mesenchymal transition (EMT) by promoting AKT phosphorylation and increasing c-Jun expression in CRC cells. Collectively, our findings indicate that GFRA1 hypomethylation can promote CRC invasion via inducing EMT, and thus, GFRA1 methylation can be used as a biomarker for the early diagnosis of highly metastasis CRC.

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A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer

Cited by 16 publications

References 30 publications

miRNA-148a-3p Regulates Immunosuppression in DNA Mismatch Repair–Deficient Colorectal Cancer by Targeting PD-L1

miRNA-148a-3p Regulates Immunosuppression in DNA Mismatch Repair–Deficient Colorectal Cancer by Targeting PD-L1

Quantitative assessment of informative immunophenotypic markers increases the diagnostic value of immunophenotyping in mature CD5‐positive B‐cell neoplasms

Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer

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