Dataset Information

Diagnostic and Prognostic Value of B4GALT1 Hypermethylation and Its Clinical Significance as a Novel Circulating Cell-Free DNA Biomarker in Colorectal Cancer.

ABSTRACT: Epigenetic modifications of glyco-genes have been documented in different types of cancer and are tightly linked to proliferation, invasiveness, metastasis, and drug resistance. This study aims to investigate the diagnostic, prognostic, and therapy-response predictive value of the glyco-gene B4GALT1 in colorectal cancer (CRC) patients. A Kaplan-Meier analysis was conducted in 1418 CRC patients (GEO and TCGA datasets) to assess the prognostic and therapy-response predictive values of the aberrant expression and methylation status of B4GALT1. Quantitative methylation-specific PCR (QMSP) and droplet digital quantitative methylation-specific PCR (dd-QMSP) were respectively used to detect hypermethylated B4GALT1 in metastasis and plasma in four cohorts of metastatic CRC cases (mCRC). Both the downregulated expression and promoter hypermethylation of B4GALT1 have a negative prognostic impact on CRC. Interestingly a low expression level of B4GALT1 was significantly associated with poor cetuximab response (progression-free survival (PFS) p = 0.01) particularly in wild-type (WT)-KRAS patients (p = 0.03). B4GALT1 promoter was aberrantly methylated in liver and lung metastases. The detection of hypermethylated B4GALT1 in plasma of mCRC patients showed a highly discriminative receiver operating characteristic (ROC) curve profile (area under curve (AUC) value 0.750; 95% CI: 0.592-0.908, p = 0.008), clearly distinguishing mCRC patients from healthy controls. Based on an optimal cut-off value defined by the ROC analysis, B4GALT1 yield a 100% specificity and a 50% sensitivity. These data support the potential value of B4GALT1 as an additional novel biomarker for the prediction of cetuximab response, and as a specific and sensitive diagnostic circulating biomarker that can be detected in CRC.

SUBMITTER: Picardo F

PROVIDER: S-EPMC6826707 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Diagnostic and Prognostic Value of <i>B4GALT1</i> Hypermethylation and Its Clinical Significance as a Novel Circulating Cell-Free DNA Biomarker in Colorectal Cancer.

Picardo Francesco F Romanelli Antonella A Muinelo-Romay Laura L Mazza Tommaso T Fusilli Caterina C Parrella Paola P Barbazán Jorge J Lopez-López Rafael R Barbano Raffaela R De Robertis Mariangela M Taffon Chiara C Bordoni Veronica V Agrati Chiara C Costantini Manuela M Ricci Francesca F Graziano Paolo P Maiello Evaristo E Muscarella Lucia Anna LA Fazio Vito Michele VM Poeta Maria Luana ML

Cancers 20191019 10

Epigenetic modifications of glyco-genes have been documented in different types of cancer and are tightly linked to proliferation, invasiveness, metastasis, and drug resistance. This study aims to investigate the diagnostic, prognostic, and therapy-response predictive value of the glyco-gene <i>B4GALT1</i> in colorectal cancer (CRC) patients. A Kaplan-Meier analysis was conducted in 1418 CRC patients (GEO and TCGA datasets) to assess the prognostic and therapy-response predictive values of the a ...[more]

PMID: 31635093

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Project description:Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality globally and is the third most prevalent cancer. The effective treatment of CRC is challenged by tumor drug resistance, underscoring the urgent need for novel therapeutic strategies. It is well recognized that epigenetic modifications, particularly DNA methylation, significantly contribute to the initiation and advancement of CRC. Tumors frequently exhibit hypermethylation of specific gene promoters alongside a general hypomethylation of genomic DNA. In normal tissues, gene promoters, particularly those of tumor suppressor genes, are typically unmethylated, whereas they are often hypermethylated in cancerous tissues. Previous studies have identified the methylation status of the CpG island within the SLC30A10 gene as a reliable biomarker for CRC. Notably, a hypermethylated phenotype is inversely correlated with SLC30A10 expression. However, the precise functional implications of SLC30A10 suppression in the context of CRC progression remain to be elucidated.). The investigation of molecular pathways involved in metal metabolism in CRC has not been conducted previously at the transcriptomic level. Furthermore, the relationship between the mutational characteristics of tumors—such as individual mutations, mutational burden, and microsatellite instability—and the activity of genes related to metal metabolic pathways has not been explored. This project aims to be the first to examine the antitumor potential of modulating the transport systems for manganese and zinc ions in CRC. The molecular function of SLC30A10 is to export zinc (Zn) and manganese (Mn) ions from the cell. Additionally, SLC30A10 plays a crucial role in mitigating Mn-induced cytotoxicity and facilitates Zn transport to early endosomes while promoting endosomal recirculation to avert Zn toxicity. Our findings indicate that overexpression of SLC30A10 is correlated with the knockout of its functional antagonist, SLC39A14 in the HuTu80 and HCT-15 cell lines.

Project description:Expression levels of LI-cadherin and miR-378e in the serum of patients with colorectal cancer, and the diagnostic value and prognostic significance in colorectal cancer were investigated. A total of 110 patients who were diagnosed with colorectal cancer in Weihai Central Hospital, from January 2012 to November 2014, were selected and enrolled in the experimental group, and 90 healthy subjects who underwent physical examination were enrolled in the control group. The expression level of miR-378e in serum was detected by reverse transcription-quantitative PCR and the expression of LI-cadherin in serum was detected by ELISA. ROC curves of LI-cadherin and miR-378e were drawn and the sensitivity and specificity of the diagnosis were estimated. The association of the expression levels of LI-cadherin and miR-378e with the survival of the patients was analyzed. LI-cadherin and miR-378e expression levels were significantly higher in the control group than those in the experimental group (P<0.001). LI-cadherin was significantly associated with the pathogenic site, the lymphatic metastasis, depth of infiltration, degree of differentiation and clinical stage (P<0.05). The sensitivity and specificity of the LI-cadherin combined with miR-378e detection were respectively 86 and 94%; the sensitivity of miR-378e detection was the highest, as well as the specificity of the combined detection. At the end of the follow-up period, the survival rates of the patients in the LI-cadherin high-expression group and miR-378e high-expression group were significantly higher than those in the low-expression groups (P<0.05). There was a significant positive correlation between the LI-cadherin and miR-378e expression levels in both the experimental and control group (r=0.5845 and 0.6356, respectively; P<0.05). In conclusion, LI-cadherin and miR-378e are expressed at low levels in colorectal cancer, suggesting that they have a good diagnostic value for colorectal cancer and can be used as biomarkers for colorectal cancer prognosis.

Project description:Circulating tumour cells (CTCs) have potential utility in various clinical applications for cancer management. The present study focused on evaluating the diagnostic role of CTCs in colorectal cancer (CRC). A total of 89 blood samples from 59 patients diagnosed with CRC and 30 healthy individuals were collected for CTC detection. The Cyttel method is an improved CTC detection strategy, which combines negative enrichment with immunofluorescence and fluorescence in situ hybridization. This method effectively detected a significant increase in total CTCs in patients with CRC (49/59) compared with those in healthy controls (3/30). A cut-off value of 2 CTCs/3.2 ml blood yielded a sensitivity of 83.05% and a specificity of 100%. Additionally, three traditional serum tumour markers, namely carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and CA72-4, were examined by immunoassays. The diagnostic sensitivity of CTCs was much higher than that of CEA, CA19-9 and CA72-4 alone or in combination, particularly in patients with early stage CRC. The combined sensitivity of CTCs and CEA reached 91.53%, which was only slightly lower than the sensitivity of all four markers combined (CTCs + CEA + CA19-9 + CA72-4). CTCs with aneuploidy of chromosome 7 or 8 were carefully distinguished, and the associations among different types of CTCs, clinicopathological characteristics and overall survival were statistically analysed. Total CTCs were revealed to be significantly associated with tumour differentiation and nerve invasion. CTCs were more likely to be detected in poorly differentiated CRC tumours than in well- and moderately-differentiated tumours (P=0.026). Furthermore, to the best of our knowledge, the present study was the first to report that CTCs with multiploidy of chromosome 7 were significantly associated with TNM stage. These CTCs exhibited a high chance of being identified in the peripheral blood of patients with late-stage CRC (stage III-IV; P=0.031). The present study suggests that the combination of CTCs and CEA may serve as an effective potential diagnostic and prognostic indicator in patients with CRC. Detection of CTCs with aneuploidy may have increased specificity in predicting highly malignant and invasive tumours in CRC management.

Dataset Information

Diagnostic and Prognostic Value of B4GALT1 Hypermethylation and Its Clinical Significance as a Novel Circulating Cell-Free DNA Biomarker in Colorectal Cancer.

Publications

Diagnostic and Prognostic Value of <i>B4GALT1</i> Hypermethylation and Its Clinical Significance as a Novel Circulating Cell-Free DNA Biomarker in Colorectal Cancer.

Similar Datasets

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