Methylation profile of colon cancer genes in colorectal precursor lesions and tumor tissue: perspectives for screening

Sobanski, Thais; Arantes, Lídia Maria Rebolho Batista; Santos, Wellington dos; Matsushita, Marcus de Medeiros; Oliveira, Marco Antônio de; Costa, M.; Carvalho, Ana Carolina de; Berardinelli, Gustavo Nóriz; Syrjänen, Kari; Reis, Rui Manuel; Guimarães, Denise Peixoto

doi:10.1080/00365521.2021.1922744

Cited by 10 publications

(7 citation statements)

References 40 publications

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“…Since gene methylation occurs in distinct genomic areas and associated with epigenetic transcriptional silencing of tumor suppressor genes, detection of gene methylation in samples from tissue or blood are becoming novel candidate targets for detecting cancer. A recent study has shown that the DNA methylation frequency of SEPT9 gene up to 91.8% (90/98) in CRC tissues, indicating a high methylation status of SEPT9 in CRC [ 33 ]. In addition, mSEPT9 DNA is found to be released into the peripheral blood from necrotic and apoptotic cancer cells during CRC carcinogenesis; thus, CRC could be determined by testing the degree of mSEPT9 in peripheral blood, which makes it likely to be a promising non-invasive tumor biomarker for CRC detection.…”

Section: Discussionmentioning

confidence: 99%

Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study

Zhang

et al. 2022

BMC Gastroenterol

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Background The detection rate of methylated Septin9 (mSEPT9) in colorectal cancer (CRC) is varied greatly across the studies. This study aimed to evaluate the diagnostic ability of mSEPT9 in CRC, and compare the diagnostic efficacy with fecal immunochemical test (FIT). Methods 326 subjects from four centers were prospectively recruited, including 179 CRC and 147 non-CRC subjects. The plasma was collected for mSEPT9 and CEA, AFP, CA125, CA153 and CA199 test, and fecal samples for FIT tests. Sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic curve were calculated to evaluate the diagnostic value of each biomarker. Results The positive rate in mSEPT9 and FIT, and the level of CEA, CA125 and CA199 were significantly higher in CRC compared with non-CRC subjects. The mSEPT9 positive rate was not associated with TNM stage and tumor stage. The sensitivity, specificity and AUC of mSEPT9 in diagnostic CRC were 0.77, 0.88 and 0.82, respectively, while the value in FIT was 0.88, 0.80 and 0.83, respectively. mSEPT9 and FIT have higher AUC value than that of CEA, CA125 and CA199. Combination of both mSEPT9 and FIT positive increased sensitivity and AUC to 0.98 and 0.83, respectively, but the specificity was declined. mSEPT9 has a slightly low sensitivity in diagnosis of colon cancer (0.87) compared with rectal cancer (0.93). Conclusion mSEPT9 demonstrated moderate diagnostic value in CRC detection, which was similar to the FIT but superior to the CEA, CA125 and CA199. Combination of mSEPT9 and FIT further improved diagnostic sensitivity in CRC. Trial registration: ChiCTR2000038319.

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Section: Discussionmentioning

confidence: 99%

Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study

Zhang

et al. 2022

BMC Gastroenterol

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“…FAM and HEX‐labeled probes were specific for methylated and unmethylated CpG sites in the promoter, respectively (Table S1). 31,32 These regions were previously analyzed by our group and found to be highly methylated in CRC tissue 15 . Additionally, we used the OligoAnalyzer Tool (https://www.idtdna.com/calc/analyzer) to assess various properties of each sequence, such as GC content, melting temperature, hairpins, dimers, and mismatches.…”

Section: Methodsmentioning

confidence: 99%

“…25 Our group recently demonstrated higher DNA methylation levels for both SEPT9 and BMP3 genes in CRC tumor tissue compared to normal tissue in a Brazilian population. 15 In the present study, we investigated the role of cell-free circulating DNA (cfDNA) methylation analysis of SEPT9 and BMP3 genes in the plasma of CRC screening program participants for detecting both adenomas and CRC lesions.…”

Section: Introductionmentioning

confidence: 99%

“…Aberrant DNA methylation occurs frequently during CRC development 11–13 . Higher methylated SEPT9 (mSEPT9) levels have been found in blood from CRC cases and in CRC tissue samples compared to normal colonoscopy biopsy samples or blood from healthy individuals 15–17 . These results led to the Epi proColon test (Epigenomics, USA), a blood‐based FDA‐approved screening test for adults with average risk for CRC, which evaluates SEPT9 methylation levels in a quantitative assay based on real‐time PCR reaction 14 .…”

Section: Introductionmentioning

confidence: 99%

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Combined SEPT9 and BMP3 methylation in plasma for colorectal cancer early detection and screening in a Brazilian population

et al. 2023

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BackgroundColorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can constitute important biomarkers of CRC detection.ObjectiveThis study aimed to evaluate the plasma methylation status of SEPT9 and BMP3 promoters as biomarkers for detection of CRC and its precursor lesions in a Brazilian population.MethodsPlasma samples from 262 participants of the CRC screening program of Barretos Cancer Hospital who had a positive fecal occult blood test and underwent colonoscopy and cancer patients were analyzed. Participants were grouped according to the worst lesion detected in the colonoscopy. Cell‐free circulating DNA (cfDNA) was bisulfite treated followed by the analysis of SEPT9 and BMP3 methylation status using a droplet digital PCR system (ddPCR). The best methylation cutoff value for group discrimination was calculated by receiver operating characteristic (ROC) curve analysis.ResultsAmong the 262 participants, 38 were diagnosed with CRC, 46 with advanced adenomas 119 with nonadvanced adenomas, three with sessile serrated lesions, and 13 with hyperplastic polyps. In 43 participants, no lesion was detected in the colonoscopy and were used as controls. The CRC group showed the highest cfDNA concentration (10.4 ng/mL). For the SEPT9 gene, a cutoff of 2.5% (AUC = 0.681) that discriminates between CRC and the control group resulted in CRC sensitivity and specificity of 50% and 90%, respectively. Concerning the BMP3 gene, a cutoff of 2.3% (AUC = 0.576) showed 40% and 90% of sensitivity and specificity for CRC detection, respectively. Combining SEPT9, BMP3 status, and age over 60 years resulted in a better performance for detecting CRC (AUC = 0.845) than the individual gene models, yielding 80% and 81% of sensitivity and specificity, respectively.ConclusionThe present study suggests that a combination of SEPT9 and BMP3 plasma methylation, along with age over 60 years, showed the highest performance in detecting CRC in a Brazilian population. These noninvasive biomarkers can potentially serve as useful tools for CRC screening programs.

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“…Currently, the majority of biomarkers used in clinical assays are designed for the early detection of cancer. Among the established CRC biomarkers, there are several based on DNA methylation changes, including NDRG4 , BMP3 [ 140 ], SEPT9 [ 141 ], BCAT1, and IKZF1 [ 142 ]. The variety of biomarkers already on the market demonstrates the successful translation from research studies to clinical assays.…”

Section: Novel Methylation Biomarkers In Crc and Metastasis Prognosismentioning

confidence: 99%

Novel Methylation Biomarkers for Colorectal Cancer Prognosis

et al. 2021

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Colorectal cancer (CRC) comprises the third most common cancer worldwide and the second regarding number of deaths. In order to make a correct and early diagnosis to predict metastasis formation, biomarkers are an important tool. Although there are multiple signaling pathways associated with cancer progression, the most recognized are the MAPK pathway, p53 pathway, and TGF-β pathway. These pathways regulate many important functions in the cell, such as cell cycle regulation, proliferation, differentiation, and metastasis formation, among others. Changes in expression in genes belonging to these pathways are drivers of carcinogenesis. Often these expression changes are caused by mutations; however, epigenetic changes, such as DNA methylation, are increasingly acknowledged to play a role in the deregulation of oncogenic genes. This makes DNA methylation changes an interesting biomarkers in cancer. Among the newly identified biomarkers for CRC metastasis INHBB, SMOC2, BDNF, and TBRG4 are included, all of which are highly deregulated by methylation and closely associated with metastasis. The identification of such biomarkers in metastasis of CRC may allow a better treatment and early identification of cancer formation in order to perform better diagnostics and improve the life expectancy.

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Methylation profile of colon cancer genes in colorectal precursor lesions and tumor tissue: perspectives for screening

Cited by 10 publications

References 40 publications

Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study

Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study

Combined SEPT9 and BMP3 methylation in plasma for colorectal cancer early detection and screening in a Brazilian population

Novel Methylation Biomarkers for Colorectal Cancer Prognosis

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