Methylated Septin9 (m<i>SEPT9</i>): A Promising Blood-Based Biomarker for the Detection and Screening of Early-Onset Colorectal Cancer

Loomans-Kropp, Holli A.; Song, Yurong; Gala, Manish; Parikh, Aparna R.; Seventer, Emily E. Van; Alvarez, Rocio; Hitchins, Megan P.; Shoemaker, Robert H.; Umar, Asad

doi:10.1158/2767-9764.crc-21-0142

Cited by 12 publications

(7 citation statements)

References 50 publications

(55 reference statements)

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“…A total of 7212 publications were queried based on our search strategy at first, and 79 eligible articles published from 2008 to 2022 were incorporated into our meta-analysis after examination of the abstract and comprehension of the full text ( Table S1 ). All included studies consisted of quantitative analysis of ctDNA concentration ( n = 11) [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ] and qualitative analysis of tumor-specific gene methylation in ctDNA ( n = 67) [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , ...…”

Section: Resultsmentioning

confidence: 99%

“…All included studies consisted of quantitative analysis of ctDNA concentration ( n = 11) [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ] and qualitative analysis of tumor-specific gene methylation in ctDNA ( n = 67) [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ,…”

Section: Resultsmentioning

confidence: 99%

“…concentration (n = 11) [40][41][42][43][44][45][46][47][48][49][50] and qualitative analysis of tumor-specific gene methylation in ctDNA (n = 67) as well as both quantitative and qualitative analysis (n = 1 [119]. Among these publications, 34 articles [51,59,60,[62][63][64][65][66][67][68][70][71][72]74,75,78,79,[81][82][83]90,91,96,[100][101][102]104,105,107,108,110,112,115,116] evaluated the diagnostic efficiency o septin9 (SEPT9) methylation for CRC. In our meta-analysis, a total population of 8076 CRC patients and 17164 control sub jects were included.…”

Section: Studies Characteristicsmentioning

confidence: 99%

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Using Circulating Tumor DNA as a Novel Biomarker to Screen and Diagnose Colorectal Cancer: A Meta-Analysis

Liang

Chen

et al. 2023

JCM

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(1) Background: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for many kinds of tumors. However, whether ctDNA could be an accurate diagnostic biomarker in colorectal cancer (CRC) remains to be clarified. The aim of this study was to evaluate the diagnostic accuracy of ctDNA in CRC. (2) Methods: PubMed, Web of Science, and Cochrane databases were searched to identify studies reporting the use of ctDNA to screen and diagnose CRC, and all relevant studies published until October 2022 were enrolled for our analysis. These studies were divided into three primer subgroups: the subgroup of quantitative or qualitative analysis of ctDNA and the subgroup of septin9 (SEPT9) methylation assay. (3) Results: A total of 79 qualified articles with 25,240 subjects were incorporated into our meta-analysis. For quantitative studies, the combined sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR) were 0.723 (95% CI: 0.623–0.803), 0.920 (95% CI: 0.827–0.966), and 23.305 (95% CI: 9.378–57.906), respectively, yielding an AUC of 0.860. The corresponding values for qualitative studies were 0.610 (95% CI: 0.566–0.651), 0.891 (95% CI: 0.878–0.909), 12.569 (95% CI: 9.969–15.848), and 0.823, respectively. Detection of SEPT9 methylation depicted an AUC of 0.879, with an SEN of 0.679 (95% CI: 0.622–0.732), an SPE of 0.903 (95% CI: 0.878–0.923), and a DOR of 20.121 (95% CI:14.404–28.106), respectively. (4) Conclusion: Blood-based ctDNA assay would be a potential novel biomarker for CRC screening and diagnosis. Specifically, quantitative analysis of ctDNA or qualitative analysis of SEPT9 methylation exhibited satisfying diagnostic efficiency. Larger sample studies are needed to further confirm our conclusions and to make the ctDNA approach more sensitive and specific.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Studies Characteristicsmentioning

confidence: 99%

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Using Circulating Tumor DNA as a Novel Biomarker to Screen and Diagnose Colorectal Cancer: A Meta-Analysis

Liang

Chen

et al. 2023

JCM

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“…Cell-free DNA exhibiting irregular methylation patterns in body fluids could be considered a potential diagnostic and prognostic tool for managing breast cancer [44]. Nonetheless, while the FDA has granted approval for SEPT9 in the early detection of colon cancer, there is still a lack of FDA-approved methylation biomarkers for breast cancer screening [45]. Gene body methylation plays a pervasive role in the modulation of gene expression and is strongly correlated with both the initiation and progression of malignant tumors [46].…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of the Gene Body in SRCIN1 Is Involved in Breast Cancer Cell Proliferation and Is a Potential Blood-Based Biomarker for Early Detection and a Poor Prognosis

Shen,

Hung,

Davis

et al. 2024

Biomolecules

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Breast cancer is a leading cause of cancer mortality in women worldwide. Using the Infinium MethylationEPIC BeadChip, we analyzed plasma sample methylation to identify the SRCIN1 gene in breast cancer patients. We assessed SRCIN1-related roles and pathways for their biomarker potential. To verify the methylation status, quantitative methylation-specific PCR (qMSP) was performed on genomic DNA and circulating cell-free DNA samples, and mRNA expression analysis was performed using RT‒qPCR. The results were validated in a Western population; for this analysis, the samples included plasma samples from breast cancer patients from the USA and from The Cancer Genome Atlas (TCGA) cohort. To study the SRCIN1 pathway, we conducted cell viability assays, gene manipulation and RNA sequencing. SRCIN1 hypermethylation was identified in 61.8% of breast cancer tissues from Taiwanese patients, exhibiting specificity to this malignancy. Furthermore, its presence correlated significantly with unfavorable 5-year overall survival outcomes. The levels of methylated SRCIN1 in the blood of patients from Taiwan and the USA correlated with the stage of breast cancer. The proportion of patients with high methylation levels increased from 0% in healthy individuals to 63.6% in Stage 0, 80% in Stage I and 82.6% in Stage II, with a sensitivity of 78.5%, an accuracy of 90.3% and a specificity of 100%. SRCIN1 hypermethylation was significantly correlated with increased SRCIN1 mRNA expression (p < 0.001). Knockdown of SRCIN1 decreased the viability of breast cancer cells. SRCIN1 silencing resulted in the downregulation of ESR1, BCL2 and various cyclin protein expressions. SRCIN1 hypermethylation in the blood may serve as a noninvasive biomarker, facilitating early detection and prognosis evaluation, and SRCIN1-targeted therapies could be used in combination regimens for breast cancer patients.

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“…Detection of tumour-derived cell-free nucleic acids in stool and blood has emerged as a promising biomarker in gastrointestinal cancers and various assays for their detection have been developed. These include the stool-based DNA multimarker (ColoGuard®) or the blood-based assay for methylated Septin 9 DNA [23,24]. However, even with extremely sensitive techniques, most early-stage tumours and precancerous lesions do not release detectable amounts of circulating tumour DNA especially for non-colorectal cancers [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Immunogenomic Biomarkers for Early Cancer Detection in Lynch Syndrome

Chambuso¹,

Mthembu²,

Kaambo³

et al. 2022

Preprint

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Lynch syndrome (LS) is an inherited disorder in which affected individuals have a significantly higher-than-average risk of developing colorectal and non-colorectal cancers, often before the age of 50 years. In LS, mutations in DNA repair genes lead to a dysfunctional post-replication repair system. As a result, the unrepaired errors in coding regions of the genome produce novel proteins, called neoantigens. Neoantigens are recognised by the immune system as foreign and trigger an immune response. Due to the invasive nature of cancer screening tests, universal cancer screening guidelines unique for LS (including colonoscopy) are poorly adhered to by LS variant heterozygotes (LSVH). Currently, it is unclear whether immunogenomic components produced as a result of neoantigen formation can be used as novel biomarkers in LS. We hypothesize that: (i) LSVH produce measurable and dynamic immunogenomic components in blood, and (ii) these quantifiable immunogenomic components correlate with cancer onset and stage. Here, we discuss feasibility and propose the potential to: (a) identify personalised novel immunogenomic biomarkers, (b) reduce invasive cancer screening tests and thus increase non-invasive cancer surveillance, (c) improve compliance and adherence to recommended cancer screening guidelines in LSVH.

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Methylated Septin9 (mSEPT9): A Promising Blood-Based Biomarker for the Detection and Screening of Early-Onset Colorectal Cancer

Cited by 12 publications

References 50 publications

Using Circulating Tumor DNA as a Novel Biomarker to Screen and Diagnose Colorectal Cancer: A Meta-Analysis

Using Circulating Tumor DNA as a Novel Biomarker to Screen and Diagnose Colorectal Cancer: A Meta-Analysis

Hypermethylation of the Gene Body in SRCIN1 Is Involved in Breast Cancer Cell Proliferation and Is a Potential Blood-Based Biomarker for Early Detection and a Poor Prognosis

Immunogenomic Biomarkers for Early Cancer Detection in Lynch Syndrome

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