<i>TFPI2</i> and <i>NDRG4</i> gene promoter methylation analysis in peripheral blood mononuclear cells are novel epigenetic noninvasive biomarkers for colorectal cancer diagnosis

Bagheri, Hadi; Mosallaei, Meysam; Bagherpour, Bahram; Khosravi, Sharifeh; Salehi, Ahmad; Salehi, Roya

doi:10.1002/jgm.3189

Cited by 33 publications

(28 citation statements)

References 55 publications

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“…On the other hand, in plasma samples, the sensitivities for detecting Ade and CRC by methylated SDC2 were 33.3% and 56.6% with a specificity of 95.6% 28 and the sensitivity by methylated TFPI2 for CRC were 88% with a specificity of 95.6%. 29 In our study, methylated SDC2 in stool samples detected 77.0% of CRC and 68.8% of Ade, with a specificity of 98.1%, while methylated TFPI2 in stool samples detected 90.2% of CRC and 75% of Ade, with a specificity of 94.3%. The specificities and sensitivities for Ade of two genes were both higher than previous study.…”

Section: Discussionsupporting

confidence: 48%

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SDC2 and TFPI2 Methylation in Stool Samples as an Integrated Biomarker for Early Detection of Colorectal Cancer

Zhang¹,

Yang²,

Wang³

et al. 2021

CMAR

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Background Detection of aberrant methylated DNA in the stool is an effective early screening method for colorectal cancer (CRC). Previously, reporters identified that syndecan-2 (SDC2) and tissue factor pathway inhibitor 2 (TFPI2) were aberrantly methylated in most CRC tissues. However, the combined diagnostic role of them remains undefined. Our research aimed at probing the role and efficiency of the methylation status of SDC2 and TFPI2 in CRC early screening by using bioinformatics analysis and clinical stool sample validation. Methods The promoter and CpG site methylation levels of SDC2 and TFPI2 and their correlation with clinicopathological characteristics of CRC were analyzed using UALCAN, Methsurv, and Wanderer. UCSC Xena was used to perform survival analyses. LinkedOmics was used to do functional network analysis. DNA was isolated and purified from stool, and quantitative methylation-specific PCR (qMSP) was applied to detect methylatedSDC2 and TFPI2. Results The results showed that promoter and most CpG site methylation levels of SDC2 and TFPI2 were significantly higher in CRC than in normal tissues. Moreover, SDC2 and TFPI2 methylation showed a positive correlation. Functional network analysis suggested that both methylated SDC2 and TFPI2 were involved in tumor cells’ metabolic programs. Besides, there was a higher positive integrated detection rate in CRC (n=61) with a sensitivity of 93.4% and in adenoma (Ade) (n=16) with a sensitivity of 81.3% than normal with a specificity of 94.3% in stool samples. What is more, integration of methylated SDC2 and TFPI2 showed a higher sensitivity and Youden index than a single gene in detecting Adeor CRC. Conclusion Our data indicate that SDC2 and TFPI2 were hypermethylated in CRC, and integrated detection of methylated SDC2 and TFPI2 in stool has the potential to be an effective and noninvasive tool of CRC early screening.

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Section: Discussionsupporting

confidence: 48%

“…26,27 Furthermore, aberrant methylation of SDC2 and TFPI2 has been detected in serum of CRC patients. 28,29 However, there is no research focus on integrated detection of these two genes in CRC screening.…”

Section: Introductionmentioning

confidence: 99%

SDC2 and TFPI2 Methylation in Stool Samples as an Integrated Biomarker for Early Detection of Colorectal Cancer

Zhang¹,

Yang²,

Wang³

et al. 2021

CMAR

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“…The ccRCC is the most common type of kidney cancers, accounting for 80% of all cases and over 30% of patients have metastases at the time of diagnosis ( 2 ). Molecular targeted drugs are the main drug therapy of metastatic renal cell carcinoma, which can prolong the OS and progression free survival (PFS) of the patients.…”

Section: Discussionmentioning

confidence: 99%

“…The ccRCC is the most common renal cell carcinoma, accounting for 80% of the cases. About 30% patients with ccRCC have already developed local or distant metastasis at the first visit, and the prognosis of these patients is often poor ( 2 ). Therefore, early diagnosis is an urgent task to improve the prognosis of ccRCC patients.…”

Section: Introductionmentioning

confidence: 99%

A Metastasis-Related lncRNA Signature Correlates With the Prognosis in Clear Cell Renal Cell Carcinoma

et al. 2021

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To explore the role of metastasis-related long noncoding RNA (lncRNA) signature for predicting the prognosis of clear cell renal cell carcinoma (ccRCC) patients. Firstly, metastasis-associated genes were identified to establish a metastasis-related lncRNA signature by statistical analysis. Secondly, the ccRCC patients were grouped into high-risk or low-risk group according to the established signature, and the different pathways between the 2 groups were identified by gene set enrichment analysis (GSEA). Finally, investigations involving PCR, transwell migration and invasion assay were carried out to further confirm our findings. The metastasis-related lncRNA signature was successfully constructed according to 7-metastasis-related genes (ADAM12, CD44, IL6, TFPI2, TGF-β1, THBS2, TIMP3). The diagnostic efficacy and the clinically predictive capacity of the signature were evaluated. Most of the values of the area under the time‐dependent receiver‐operating characteristic (ROC) were greater than 0.70. The nomogram constructed by integrating clinical data and risk scores confirmed that the risk score calculated from our signature was a good prognosis predictor. GSEA analysis showed that some tumor-related pathways were enriched in the high-risk group, while metabolism-related pathways were enriched in the low-risk group. In carcinoma tissues, the SSR3-6, WISP1-2 were highly expressed, but the expression of UBAC2-6 was low there. Knocking down SSR3-6 decreased the ability of migration and invasion in ccRCC cells. In conclusion, we successfully constructed a metastasis-related lncRNA signature, which could accurately predict the survival and prognosis of ccRCC patients.

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“…In CRC, multiple blood-based diagnostic methylation biomarkers have been studied, including ALX4, APC, HLTF, MGMT, NEUROG1, RASSF2A, Wif-1, FBN2, PI6, TMEFF1, SDC2, TAC1, THBD, and TFPI2 [ 96 , 102 , 103 , 104 ]. It is likely, and certainly conceivable, that a biomarker panel of methylated genes will be translated into a clinical setting for CRC screening in the near future [ 105 ].…”

Section: Novel Biomarkers In Crc—an Epigenetic-based Approachmentioning

confidence: 99%

Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers?

et al. 2021

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Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: “Screening”, “Diagnosis”, and “Biomarkers for CRC”. American and European clinical trials in progress were included as well.

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TFPI2 and NDRG4 gene promoter methylation analysis in peripheral blood mononuclear cells are novel epigenetic noninvasive biomarkers for colorectal cancer diagnosis

Cited by 33 publications

References 55 publications

SDC2 and TFPI2 Methylation in Stool Samples as an Integrated Biomarker for Early Detection of Colorectal Cancer

SDC2 and TFPI2 Methylation in Stool Samples as an Integrated Biomarker for Early Detection of Colorectal Cancer

A Metastasis-Related lncRNA Signature Correlates With the Prognosis in Clear Cell Renal Cell Carcinoma

Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers?

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