Dataset Information

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

ABSTRACT:

Background

Colorectal 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.

Objective

This 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.

Methods

Plasma 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.

Results

Among 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.

Conclusion

The 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.

SUBMITTER: Lima AB

PROVIDER: S-EPMC10469661 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Lima Adhara Brandão AB Dos Reis Mariana Bisarro MB Matsushita Marcus M Dos Reis Monise Tadin MT de Oliveira Marco Antônio MA Reis Rui Manuel RM Guimarães Denise Peixoto DP

Cancer medicine 20230620 15

<h4>Background</h4>Colorectal 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.<h4>Objective</h4>This 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.<h4>Methods</h4>Plasma samples from 262 participants of the CRC screening progr ...[more]

PMID: 37338022

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Project description:BackgroundCervical cancer screening by combined cytology and HPV test has reduced the incidence of cervical cancer, but cytological screening lacks a higher sensitivity while HPV testing possesses a lower specificity. Most patients with invasive cervical cancer are treated with radiotherapy. However, insensitivity to radiotherapy leads to poor efficacy.MethodsIllumina Methylation EPIC 850k Beadchip was used for genomic screening. We detected methylation of SEPT9 and mRNA expression in different cervical tissues by using methylation-specific PCR and qRT-PCR. Then using CCK8, migration assay, and flow cytometry to detect the biological function and irradiation resistance of SEPT9 in vitro and in vivo. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation (CoIP) were used to find the interacting gene with SEPT9. Immunostaining of CD206 in cervical cancer and polarization of macrophages (M2) were evaluated by immunofluorescence and WB. The Cancer Genome Atlas (TCGA) database was used for screening the potential miRNAs induced by SEPT9.ResultsHyper-methylation of SEPT9 detects cervical cancer and normal tissues, normal+CIN1 and CIN2+CIN3+cancer with high sensitivity and specificity (AUC = 0.854 and 0.797, respectively, P < 0.001). The mRNA and protein expression of SEPT9 was upregulated in cervical cancer tissues when compared to para-carcinoma tissues. SEPT9 promotes proliferation, invasion, migration, and influences the cell cycle of cervical cancer. SEPT9 interacted with HMGB1-RB axis increases irradiation resistance. Furthermore, SEPT9 mediated miR-375 via the tumor-associated macrophages (TAMs) polarization, affecting the resistance to radiotherapy in cervical cancer.ConclusionsThese findings give us the evidence that SEPT9 methylation could be a biomarker for cervical cancer diagnoses. It promotes tumorigenesis and radioresistance of cervical cancer by targeting HMGB1-RB axis and causes polarization of macrophages by mediating miR-375. We suggest SEPT9 could be a potential screening and therapeutic biomarker for cervical cancer.

Dataset Information

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

Background

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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