Toxic chemicals and epigenetic biomarkers associated with cancer have been used successfully in clinical diagnostic screening of feces and urine from individuals, but they have been underutilized in a global setting. We analyzed peer-reviewed literature to achieve the following: (i) compile epigenetic biomarkers of disease, (ii) explore whether research locations are geographically aligned with disease hotspots, and (iii) determine the potential for tracking disease-associated epigenetic biomarkers. Studies (n = 1145) of epigenetic biomarkers (n = 146) in urine and feces from individuals have established notable diagnostic potential for detecting and tracking primarily gastric and urinary cancers. Panels with the highest sensitivity and specificity reported more than once were SEPT9 (78% and 93%, respectively) and the binary biomarker combinations GDF15, TMEFF2, and VIM (93% and 95%), NDRG4 and BMP3 (98% and 90%), and TWIST1 and NID2 (76% and 79%). Screening for epigenetic biomarkers has focused on biospecimens from the U.S., Europe, and East Asia, whereas data are limited in regions with similar/higher disease incidence rates (i.e., data for New Zealand, Japan, and Australia for colorectal cancer). The epigenetic markers discussed here may aid in the future monitoring of multiple cancers from individual- to population-level scales by leveraging the emerging science of wastewater-based epidemiology (WBE).

Primary live cancer (PLC), including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). This meta-analysis was conducted to evaluate the diagnostic efficacy of blood methylated septin 9 gene (mSEPT9) for PLC and to analyze its performance across various subgroups.

We conducted a comprehensive search across PubMed, the Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI), covering research up to May 10, 2024. The pooled sensitivity, specificity, diagnostic odds ratios, and area under the summary receiver operating characteristic (AUC) were calculated for the diagnostic performance of mSEPT9 for PLC. The quality of the studies was assessed using the QUADAS-2 tool, and the meta-analysis was performed using Stata16.0 software.

Ten articles with 2,182 participants were included in the meta-analysis. The pooled sensitivity of mSEPT9 for detecting primary liver cancer was 0.51 (95% confidence interval [CI]: 0.37-0.65), and the pooled specificity was 0.93 (95% CI: 0.78-0.98). The pooled diagnostic odds ratio was 13 (95% CI: -58), and the area under the Summary Receiver Operator Characteristic Curve was 0.75 (95% CI: 0.71-0.79). Subgroup analyses showed that ICC, case-control studies, qPCR and Asian populations had higher specificities (0.99 [95% CI: 0.97-1.00], 0.93 [95% CI: 0.91-0.95], 0.90 [95% CI: 0.88-0.92] and 0.94 [95% CI: 0.92-0.96], respectively) and diagnostic odds ratios (62.04 [95% CI: 6.53-589.53], 17.62 [95% CI: 4.03-76.99], 13.03 [95% CI: 2.01-84.63] and 14.19 [95% CI: 2.42-83.11], respectively) compared to hepatocellular carcinoma, cohort Study, and Euramerican populations.

This study confirmed that mSEPT9 in blood has high specificity and moderate sensitivity for detecting primary liver cancer. The diagnostic performance of mSEPT9 varied across different subgroups, limiting its use as an independent screening tool and necessitating its use in conjunction with other methods for confirmatory diagnostics.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024549669.

Colorectal cancer (CRC) is the third most prevalent cancer globally and poses a significant health threat, making early detection crucial. This review paper explored emerging detection methods for early screening of CRC, including gut microbiota, metabolites, genetic markers, and artificial intelligence (AI)-based technologies. Current screening methods have their respective advantages and limitations, particularly in detecting precursors. First, the importance of the gut microbiome in CRC progression is discussed, highlighting how specific microbial alterations can serve as biomarkers for early detection, potentially enhancing diagnostic accuracy when combined with traditional screening methods. Next, research on metabolic reprogramming illustrates the relationship between metabolic changes and CRC, with studies developing metabolite-based detection models that show good sensitivity for early diagnosis. In terms of genetic markers, methylated DNA markers like SEPTIN9 have demonstrated high sensitivity, although further validation across diverse populations is necessary. Lastly, AI technology has shown immense potential in improving adenoma detection rates, significantly enhancing the quality of colonoscopic examinations through image recognition techniques. This review aims to provide a comprehensive perspective on new strategies for CRC screening, emphasizing the potential of noninvasive detection technologies and the prospects of AI and genomics in clinical applications. Despite several challenges, this review advocates for future large-scale prospective studies to validate the effectiveness and cost-effectiveness of these new screening methods while promoting the implementation of screening protocols tailored to individual characteristics.

Following neoplasms of the lung and breast, colorectal cancer (CRC) is the third most frequent malignancy globally. Screening for CRC at the age of 50 years is strongly encouraged for prompt earlier diagnosis owing to prognoses being greatly correlated with time of detection and cancer staging.

This review aimed to elucidate the most recent advancements in the detection of CRC, with an emphasis on the latest innovations in diagnostic molecular biomarkers in conjunction with radiological imaging alongside stool-based tests for CRC screening.

A comprehensive review of the literature was performed, focusing on specific terms in different electronic databases, including that of PubMed/MEDLINE. Keywords pertaining to "colorectal cancer," "diagnosis," "screening," "imaging," and "biomarkers," among others, were employed in the search strategy. Articles screened and evaluated were deemed relevant to the study aim and were presented in the medium of the English language.

There have been several innovations in the diagnostics and identification of CRC. These generally comprise molecular biomarkers, currently being studied for suitability in disease detection. Examples of these include genetic, epigenetic, and protein biomarkers. Concurrently, recent developments in CRC diagnostics highlight the advancements made in radiological imaging that offer precise insights on tumor biology in addition to morphological information. Combining these with statistical methodologies will increase the sensitivity and specificity of CRC diagnostics. However, putting these strategies into reality is hampered by several issues.

Progress in diagnostic technology alongside the identification of a few prognostic predictive molecular biomarkers suggested great promise for prompt detection and management of CRC. This clearly necessitates further efforts to learn more in this specific sector.

Early detection for colorectal cancer (CRC) can enhance the patient prognosis. We aimed to validate the combined multi-gene detection in plasma of Septin9, SDC2, KCNQ5, and IKZF1 for early diagnosing of CRC in this prospective study.

Overall, 124 participants including 45 CRC patients, 8 advanced adenoma patients, 34 small polyp patients, and 37 normal controls who underwent colonoscopy were enrolled. The carcinoembryonic antigen (CEA) test and methylation tests for Septin9, SDC2, KCNQ5, and IKZF1 were performed. Sensitivity, specificity, and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve were utilized to evaluate the diagnostic value of each biomarker. Additionally, the association between the positive rates of methylated Septin9, SDC2, KCNQ5, and IKZF1 and the clinicopathological characteristics of CRC was also analyzed.

The positive detection rate of multi-gene methylation in CRC patients was 86.67%, for stage I and stage II patients, the positive rates were 90.91% and 87.50%, both of which were significantly higher than CEA, which had rates of 55.56%, 18.18% and 56.25% for the corresponding stages. In patients with advanced adenomas and small polyps, the positive rates for the four-gene combined test were 62.50% and 52.94%, respectively, which were markedly higher than the CEA rates of 12.50% and 14.71%. AUC of the ROC curve indicated that the diagnostic value of the multi-gene test for CRC was superior to that of any single gene. Correlation analysis revealed that the positive rate of the test was not affected by patients' clinicopathological characteristics.

A combination of methylated Septin9, SDC2, KCNQ5, and IKZF1 test has the potential for early diagnosis of CRC patients, advanced adenoma patients, and small polyp patients.

Colorectal cancer (CRC) is a rising threat, necessitating accurate early diagnosis.

This meta-analysis scrutinised methylated septin 9 (SEPT9) and carcinoembryonic antigen (CEA) in CRC.

From January 2012 to December 2022, databases including PubMed and Google Scholar were explored for English publications.

The meta-analysis revealed SEPT9's superior diagnostic potential, boasting 71% sensitivity and 91% specificity, outshining CEA (49% and 53%). Notably, an 8-study analysis found a positive correlation between tumour grade and elevated CEA and SEPT9 levels, particularly in stages 3 and 4.

This meta-analysis supports SEPT9 as a potent CRC marker, urging its integration into diagnostic frameworks for enhanced precision and early intervention. The observed link between tumour grade and biomarker levels enhances clinical relevance. Implementing these findings promises improved CRC diagnosis precision, contributing to enhanced treatment outcomes and patient survival. Advocating for SEPT9's inclusion alongside traditional markers like CEA, this study pioneers more effective colorectal cancer management strategies.

Circulating tumor DNA (ctDNA) methylation, an innovative liquid biopsy biomarker, has emerged as a promising tool in early cancer diagnosis, monitoring, and prognosis prediction. As a noninvasive approach, liquid biopsy overcomes the limitations of traditional tissue biopsy. Among various biomarkers, ctDNA methylation has garnered significant attention due to its high specificity and early detection capability across diverse cancer types. Despite its immense potential, the clinical application of ctDNA methylation faces substantial challenges pertaining to sensitivity, specificity, and standardization. In this review, we begin by introducing the basic biology and common detection techniques of ctDNA methylation. We then explore recent advancements and the challenges faced in the clinical application of ctDNA methylation in liquid biopsies. This includes progress in early screening and diagnosis, identification of clinical molecular subtypes, monitoring of recurrence and minimal residual disease (MRD), prediction of treatment response and prognosis, assessment of tumor burden, and determination of tissue origin. Finally, we discuss the future perspectives and challenges of ctDNA methylation detection in clinical applications. This comprehensive overview underscores the vital role of ctDNA methylation in enhancing cancer diagnostic accuracy, personalizing treatments, and effectively monitoring disease progression, providing valuable insights for future research and clinical practice.

To evaluate the performance of stool methylated syndecan2 (mSDC2), methylated septin9 (mSEPT9), fecal occult blood test (FOBT), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) in detecting colorectal neoplasia and adenomas.

Blood-borne CEA, CA125, and CA199 levels were measured by electrochemiluminescence. The SDC2 methylation was detected by Methylation Detection Kit for Human SDC2 Gene (Real time PCR), and the SEPT9 methylation was detected by the Septin9 Gene Methylation Detection Kit based on PCR fluorescent probe assay. The colonoscopy combined with tissue biopsy pathology was used as a validation criterion for colorectal neoplasia.

In detecting colorectal neoplasia, the AUCs of mSDC2, FOBT and mSEPT9 were 0.935 (95% CI: 0.915-0.956, P<0.001), 0.824 (95% CI: 0.617-1.000, P<0.001) and 0.671 (95% CI: 0.511-0.831, P<0.001), respectively. The sensitivity of mSDC2, FOBT and mSEPT9 were 100.0%, 66.7% and 40.0%, respectively. But the AUC of CEA, CA125 and CA199 were not statistically significant for colorectal neoplasia (all P>0.05). The combined application of mSEPT9 and mSDC2 showed the best predictive performance (AUC: 0.956, 95% CI: 0.887~1.000). For adenomas, the AUC of FOBT was extremely low (AUC: 0.524, 95% CI: 0.502-0.545, P=0.004). The CEA, CA125, CA199, mSEPT9 and mSDC2 were not statistically significant in detecting adenomas (all P>0.05).

For individual tests, FOBT and mSDC2 are relatively better indicators for detecting colorectal neoplasia compared to mSEPT9, CEA, CA125 and CA199. The combined form of mSEPT9 and mSDC2 to detect colorectal neoplasia has good predictive performance. However, none of these indicators demonstrated significant predictive power for detecting adenomas in our study.

To explore the medical significance of methylated septin9 (mSEPT9) in monitoring recurrence and prognostic assessment in individuals with surgically treated colorectal cancer (CRC).

To investigate the role of Septin9 in colorectal cancer, we utilized the TIMER2.0 database to analyze its differential expression between tumor tissues and adjacent normal tissues. Colorectal cancer RNA-seq data from the TCGA database was downloaded and curated. The clinical relevance of mSEPT9 in colorectal cancer was explored by examining the correlation between Septin9 methylation levels and clinical characteristics using UALCAN and MethSurv software. Peripheral blood samples were obtained from 130 CRC subjects who underwent surgery for the detection of mSEPT9 and carcinoembryonic antigen (CEA) expression, along with collection of clinicopathological data such as age, gender, tumor site, TNM stage, and tumor differentiation. Patients were followed up for at least 3 years post-surgery until the death or final follow-up dates (31/12/2022). Additionally, peripheral blood samples were collected from 30 colorectal cancer surgery patients for mSEPT9 detection before and 7 days after surgery.

Through bioinformatic database analysis, we identified higher expression levels of SEPT9 mRNA in most tumor tissues compared to normal tissues. Similarly, both paired and unpaired CRC tissues exhibited elevated expression of Septin9 when compared to normal tissues. Following GO and KEGG analysis of Septin9 target genes, we discovered their significant associations with ncRNA metabolic processes, ribonucleoprotein complex biogenesis, spliceosomes, and viral carcinogenesis. Furthermore, the overexpression of mSeptin9 was observed in CRC tissues, and it demonstrated a correlation with colon cancer staging and histologic classification. In our clinical sample study, The positive rate of mSEPT9 in CRC patients 7 days after surgery was 43.44% lower than that of preoperative. The differences in TNM stage, tumor differentiation degree, and preoperative CEA expression level between the preoperative mSEPT9 positive and negative groups of CRC were statistically significant (P < 0.05). Recurrence free survival (RFS) and overall survival (OS) were shorter in the preoperative mSEPT9-positive group, meaning preoperative mSEPT9 status was a risk factor for CRC recurrence and prognosis (P < 0.05). The sensitivity, specificity, and AUC value of preoperative mSEPT9 and CEA levels for predicting postoperative recurrence in CRC patients were 88% vs. 72%, 56.19% vs. 55.24%, and 0.721 vs. 0.636 respectively, well the AUC value of the combined prediction of postoperative recurrence was 0.758.

The detection of mSEPT9 combined with CEA in preoperative plasma helps predict recurrence in colorectal cancer patients.

Background: Early screening for colorectal cancer (CRC) has the potential to improve patient prognosis, but current screening methods are limited. In this prospective study, we aimed to evaluate the multigene (Septin9, SDC2, KCNQ5, and IKZF1) detection in patient plasma for CRC diagnosis. Methods: Overall, 67 participants were enrolled, including 31 patients with CRC, 17 patients with colorectal polyp, and 19 normal controls who underwent colonoscopy. Carcinoembryonic antigen (CEA) and Septin9, SDC2, KCNQ5, and IKZF1 methylation tests were performed. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve were used to evaluate the diagnostic value of each biomarker. The association between positive rates of methylated Septin9, SDC2, KCNQ5, and IKZF1 and the clinicopathological characteristics of CRC was also analyzed. Results: The positive rate of multigene methylation detection was 87.1% (27/31) in patients with CRC, which was higher than single indicators: CEA (51.61%, 16/31), Septin9 (41.94%, 13/31), SDC2 (41.94%, 13/31), KCNQ5 (58.06%, 18/31), and IKZF1 (32.26%, 10/31). In the colorectal polyp group, the rate of multigene methylation detection is 88.24% (15/17), which was also higher than single indicator: CEA (17.65%, 3/17), Septin9 (11.76%, 2/17), SDC2 (64.71%, 11/17), KCNQ5 (58.82%, 10/17), and IKZF1 (35.29%, 6/17). The ROC curves further showed better diagnostic value of the multigene test for CRC than any single gene. Correlation analysis found that the positive rate of the test was not affected by patients' clinicopathologic characteristics. Conclusion: The combination of methylated Septin9, SDC2, KCNQ5, and IKZF1 tests is preferable to individual gene tests for patients with CRC and polyp.

Gene methylation and the immune-related tumor microenvironment (TME) are highly correlated in tumor progression and therapeutic efficacy. Although both of them can be used to predict the clinical outcomes of colorectal cancer (CRC) patients, their predictive value is still unsatisfactory. Whether a combination risk model comprising these two prediction parameters performs better predictive effectiveness than independent factor is still unclear. Methylated Septin9 (mSEPT9) is an early diagnosis biomarker of CRC, in this study, we aimed to investigate mSEPT9-related biomarkers of immunosuppressive TME and identify the value of the combination risk model in predicting the clinical outcomes of CRC.

Immunofluorescence staining was performed to clarify the correlation between intratumoral IL-10+ Treg infiltration and mSEPT9 in peripheral blood. Survival time, response to 5-fluorouracil (5-FU)-based chemotherapy and PD-1 blockade, and the probability of recurrence or metastasis were analyzed in study (197 CRC samples) and validation (195 CRC samples) sets to evaluate the efficacy of combination risk model. Potential mechanisms were explored by mRNA sequencing.

Hypermethylated SEPT9 in the peripheral blood of patients with CRC (stage I-III, and stage IV with resectable M1) before radical resection was positively correlated with high intratumoral IL-10+ Treg infiltration. The high-risk model revealed poor overall survival and progression-free survival, inferior therapeutic response to 5-FU-based chemotherapy and PD-1 blockade, and high probability of recurrence or metastasis. The underlying mechanisms may be associated with the increase in mSEPT9 and mediation of IL-10 via methionine metabolic reprogramming-induced infiltration of IL-10+ Tregs in the TME, which promotes tumor progression and resistance to 5-FU-based chemotherapy and PD-1 blockade.

The combination risk model of peripheral mSETP9 and intratumoral IL-10+ Treg infiltration in CRC can effectively predict prognosis, responsiveness to 5-FU-based chemotherapy and PD-1 blockade, and the probability of recurrence or metastasis. Therefore, this model can be used for precision treatment of CRC.

Rectal cancer (RC) occupies a leading position in the structure of oncological morbidity and mortality. Aberrant methylation of tumor-suppressor genes and hypomethylation of retrotransposons were shown to be detectable in cell-free DNA, circulating in the blood (cfDNA) of cancer patients, indicating the possibility to use them as diagnostic and prognosis markers.

Evaluation of the changes in the methylation level of LINE-1 elements and SEPTIN9 and IKZF1 genes in the cell-surface-bound cfDNA (csb-cfDNA) from the blood of RC patients after antitumor therapy at a long-term follow-up.

Blood samples were obtained from RC patients (n = 25) before treatment, after preoperative chemotherapy (3 courses according to the XELOX scheme), 10-15 days after surgery, and every 3 months during 12 months of dynamic observation. The methylation level of LINE-1, SEPTIN9, and IKZF1 in the csb-cfDNA was evaluated by quantitative methyl-specific PCR.

The LINE-1 methylation level in the csb-cfDNA increased 1.6 times in RC patients after chemotherapy and 3 times after tumor resection versus methylation level before therapy. The SEPTIN9 gene methylation level in the csb-cfDNA decreased by 1.7 times in RC patients after chemotherapy and by 2.3 times after tumor resection compared with the values before the treatment. The IKZF1 gene methylation level decreased by 2 times in RC patients after combined therapy. Notably, all patients with relapses (n = 5) showed an increase in methylation level for the SEPTIN9 and IKZF1 genes and a decrease of methylation level for the LINE-1 elements by 2 times or more in comparison with the level 10-15 days after surgery. There were no changes in the circulating SEPTIN9, IKZF1, and LINE-1 methylation levels during the 12-month follow-up period after the combined therapy of RC patients (n = 20) without relapses.

The results indicate that SEPTIN9, IKZF1, and LINE-1 methylation levels in the csb-cfDNA are potential markers of the effectiveness of antitumor therapy and early detection of relapse in RC patients.

This study aimed to investigate clinical diagnostic values of mSEPT9 combined with NLR, PLR and LMR in CRC.

329 subjects composed of 120 CRC patients, 105 polyps patients and 104 healthy participants were prospectively recruited. Clinicopathologic features were collected and analyzed. Plasma samples were collected for mSEPT9, NLR, PLR and LMR test. The sensitivity, specificity and AUC of each biomarker separately or in combination were estimated by the ROC curve.

The levels of NLR, PLR and the PDR of mSEPT9 in CRC patients were significantly higher than those in non-CRC subjects, while LMR was the opposite. The PDR of mSEPT9 in CRC patients was significantly correlated with age, tumor size, tumor stage and M stage. ROC curve analysis demonstrated moderate diagnostic values of mSEPT9, NLR, PLR and LMR in CRC patients with AUC of 0.78 (Se = 0.68, and Sp = 0.89), 0.78 (Se = 0.68, and Sp = 0.83), 0.80 (Se = 0.68, and Sp = 0.81), and 0.77 (Se = 0.72, and Sp = 0.73), respectively. Moreover, combination of these four biomarkers dramatically enhanced the diagnostic accuracy of CRC (AUC = 0.92, Se = 0.90, and Sp = 0.87), especially for CRC patients with large tumors (AUC = 0.95) or distal metastasis (AUC = 0.95).

mSEPT9, NLR, PLR and LMR showed the potential to be reliable biomarkers for the diagnosis of CRC. And the combined application of these biomarkers further improved the diagnostic accuracy of CRC significantly.

This study was designed to compare the diagnostic efficacy of mSEPT9 to four blood markers (CEA, CA19-9, platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR)). In addition, we aimed to determine the combined diagnostic efficacy of mSEPT9, CEA, CA19-9, PLR and NLR in colorectal cancer.

A total of 567 participants were enrolled in the study, including 308 CRC patients, 61 colorectal polyp patients and 198 healthy subjects confirmed by colonoscopy and/or tissue biopsy. Plasma samples were collected for tests.

The positive rate of mSEPT9 in CRC (71.8%) was markedly higher than that in either the colorectal polyps group (27.9%) or the healthy controls (6.1%) (P < 0.001). The levels of CEA, CA19-9, NLR and PLR in the CRC group were significantly higher than those in the non-CRC groups (P < 0.05). ROC curves comparison analyses showed that the diagnostic efficacy of mSEPT9 alone in CRC was significantly higher than CEA, CA19-9, NLR and PLR alone. The combination of mSEPT9 with CEA, CA19-9 and PLR showed superior diagnostic value. In addition, binary logistic regression was also used to build a better model for clinical diagnosis of CRC. On univariable analyses, age, mSEPT9, CEA, CA 19-9, PLR and NLR were independent predictors of CRC. When these covariates were fitted in multivariable models, the ones with positive detection of mSEPT9, CEA, CA 19-9 and PLR were more likely to have CRC.

This research revealed a significant association between mSEPT9 status and the clinicopathological characteristics of CRC patients, and the combination of mSEPT9, CEA, CA19-9 and PLR could significantly improve diagnostic efficacy in CRC.

Colorectal cancer (CRC) has high incidence and mortality rates, and the emergence and application of CRC screening have helped us effectively control the occurrence and development of CRC. Currently, common international screening methods include tests based on feces and blood, and examination methods that allow for visualization, such as sigmoidoscopy and colonoscopy. Some methods have been widely used, whereas others such as multi-target stool RNA test are still being explored and developed, and are expected to become front-line screening methods for CRC in the future. The choice of screening method is affected by external conditions and the patients' situation, and the clinician must choose an appropriate strategy according to the actual situation and the patient's wishes. This article introduces various CRC screening methods and analyzes the factors relevant to the screening strategy.

Colorectal cancer (CRC) is one of the most common malignancies, with a high incidence and mortality worldwide. Methylated Septin 9 (mSEPT9) has been used clinically as an auxiliary tool for CRC screening. The aim of the present study was to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism with the risk of CRC and the methylation status of Septin 9 in CRC.

Information of 540 patients with a confirmed diagnosis of CRC and with a physical examination were utilized to assess the association of the MTHFR rs1801133 polymorphism with CRC and the methylation of SEPT9. MTHFR rs1801133 polymorphism was genotyped using polymerase chain reaction (PCR). The commercial Septin 9 Gene Methylation(mSEPT9) Detection Kit was used for plasma SEPT9 methylation analysis.

Among 540 patients, 61.48% were men and the median age was 54.47 ± 13.14. 65.37% of all colorectal tumors developed in the rectum. 195 patients had negative mSEPT9 methylation, while 345 had positive results. 87 individuals with stage I, 90 with stage II, 287 with stage III, and 76 with stage IV colorectal cancer were included in the sample. The results demonstrated that the positivity rate and degree of methylation of mSEPT9 were remarkably higher in patients with more advanced TNM stages than in those with less advanced stages. The frequencies of the MTHFR rs1801133 CC genotype and allele C carriers in patients with CRC were significantly higher than those in healthy individuals (P = 0.006 and P = 0.001, respectively). The positivity rate of the mSEPT9 assay was significantly higher among the MTHFR rs1801133 TT genotype and allele T carriers than among the CC and allele C carriers respectively. The MTHFR rs1801133 TT genotype and allele T carriers were positively associated with the methylation of SEPT9 (OR = 3.320, 95% CI 1.485-7.424, P = 0.003 and OR = 1.783, 95% CI 1.056-3.010, P = 0.030, respectively).

In conclusion, individuals harboring the MTHFR rs1801133 CC genotype had a higher risk of CRC and the MTHFR rs1801133 TT carriers were more susceptible to Septin 9 gene methylation.

The lymphocyte-to-monocyte ratio (LMR) is an indicator of inflammation in blood routine tests; however, little is known about its screening value in patients with colorectal cancer (CRC). The aim of this study was to explore the screening value of LMR and methylated Septin9 (mSEPT9) in CRC patients. The clinical data of 420 patients with CRC, 61 with adenomatous polyps, and 175 healthy individuals from 2018 to 2022 were retrospectively analyzed, and corresponding predictive nomograms were established. The results showed that the levels of LMR and mSEPT9 in the CRC group were significantly lower than those in the control group (P < .05). Meanwhile, the levels of LMR and mSEPT9 in right-sided CRC were significantly lower than those in left-sided CRC (P < .05). With the progression of CRC from stage I to IV, the levels of LMR and mSEPT9 also decreased gradually, and the levels of mSEPT9 in stages III and IV were significantly lower than those in stages I and II (P < .05). Receiver operating curve (ROC) results showed that mSEPT9 had the highest single diagnostic value for CRC, with an area under curve (AUC) of 0.810. The LMR with mSEPT9 combination showed the best combined diagnostic value for CRC, with AUC of 0.885. When the cutoff values of mSEPT9 and LMR were taken as 43.835 and 3.365, the sensitivity and specificity of this combination reached 82.3% and 84.6%, respectively. Our findings suggest that LMR and mSEPT9 differ in non-tumor group and CRC groups with different subtypes and stages, LMR with mSEPT9 combination can further improve sensitivity, and the novel predictive nomogram for CRC based on LMR and mSEPT9 can be further promoted.

Colorectal cancer (CRC) is one of the significant global health concerns with an increase in cases. Regular screening tests are crucial for early detection as it is often asymptomatic in the initial stages. Liquid biopsies, a non-invasive approach that examines biomarkers in biofluids, offer a promising future in diagnosing and screening cancer. Circulating-tumour DNA (ctDNA) is the genetic material in biofluids released into the circulatory system by cells. ctDNA is a promising marker for monitoring patients since cancer cells display distinct DNA methylation patterns compared to normal cells. The potential of our research to contribute to early detection and improved patient outcomes is significant.

The primary objective of this research project was to explore the HAND1 methylation levels in plasma ctDNA as a potential biomarker for diagnosing CRC and evaluate the methylation level of the well-established gene SPET9 to compare it with the methylation level of HAND1.

Plasma samples were collected from 30 CRC patients and 15 healthy individuals, with CRC samples obtained pre-treatment. ctDNA was extracted and treated with bisulfite for methylation status assessment. Quantitative methylation-specific PCR (qMS-PCR) was performed for HAND1 and SEPT9, using β-actin (ACTB gene) as a reference. The study aims to evaluate the potential of these genes as diagnostic biomarkers for CRC, contributing to early detection and improved patient outcomes.

Our study yielded significant results: 90% of CRC patients (27 out of 30) had hypermethylation in the SEPT9 gene, and 83% (25 out of 30) exhibited hypermethylation in the HAND1 gene. The methylation levels of both genes were significantly higher in CRC patients than in healthy donors. These findings underscore the potential of SEPT9 and HAND1 methylation as promising biomarkers for diagnosing CRC, potentially leading to early detection and improved patient outcomes.

These findings highlight the potential of SEPT9 and HAND1 methylation as promising biomarkers for diagnosing CRC. However, further research and validation studies are needed to confirm these findings and to explore their clinical utility in CRC diagnosis and management.

Common detection methods in practice for diagnosing colorectal cancer (CRC) are painful and invasive leading to less participation of individuals for CRC diagnosis. Whereas, improved or enhanced imaging systems and other minimally invasive techniques with shorter detection times deliver greater detail and less discomfort in individuals. Thus, this review is a summary of the diagnostic tests, ranging from the simple potential use in developing a flexible CRC treatment to the patient's potential benefits in receiving less invasive procedures and the advanced treatments that might provide a better assessment for the diagnosis of CRC and reduce the mortality related to CRC.

Metastatic prostate cancer (mPCA) poses challenges in treatment response assessment, particularly in cases where prostate-specific antigen (PSA) levels do not reliably indicate a response. Liquid biopsy, focusing on circulating cell-free DNA (ccfDNA) methylation analysis as a proxy for circulating tumor DNA, offers a non-invasive and cost-effective approach. This study explores the potential of two methylation markers, short stature homeobox 2 (SHOX2) and Septin 9 (SEPT9), as on-mPCA-treatment biomarkers.

Plasma samples were collected from 11 mPCA patients undergoing various treatments. Quantitative assessment of hypermethylated SHOX2 (mSHOX2) and SEPT9 (mSEPT9) levels in ccfDNA was conducted through methylation-specific real-time PCR. Early and overall dynamics of PSA, mSHOX2, and mSEPT9 were analyzed. Statistical evaluation employed Wilcoxon tests.

mSHOX2 demonstrated a significant decline post-treatment in patients with a radiographic treatment response as well as in an early treatment setting. mSEPT9 and PSA exhibited non-significant declines. In individual cases, biomarker dynamics revealed unique patterns compared to PSA.

mSHOX2 and mSEPT9 exhibit dynamics on mPCA treatment. This proof-of-concept study lays the groundwork for further investigation into these markers as valuable additions to treatment response monitoring in mPCA. Further validation in larger cohorts is essential for establishing clinical utility.

Glutaredoxin 2 (Grx2; Glrx2) is a glutathione-dependent oxidoreductase located in mitochondria, which is central to the regulation of glutathione homeostasis and mitochondrial redox, and plays a crucial role in highly metabolic tissues. In response to mitochondrial redox signals and oxidative stress, Grx2 can catalyze the oxidation and S-glutathionylation of membrane-bound thiol proteins in mitochondria. Therefore, it can have a significant impact on cancer development. To investigate this further, we performed an immunohistochemical analysis of Grx2 protein expression in colon adenocarcinoma samples collected from patients with primary colon adenocarcinoma (stage I and II) and patients with metastasis to regional lymph nodes (stage III). The results of our study revealed a significant relationship between the immunohistochemical expression of Grx2 and tumor histological grade, depth of invasion, regional lymph node involvement, angioinvasion, staging, and PCNA immunohistochemical expression. It was found that 87% of patients with stage I had high levels of Grx2 expression. In contrast, only 33% of patients with stage II and 1% of patients with stage III had high levels of Grx2 expression. Moreover, the multivariate analysis revealed that the immunohistochemical expression of Grx2 protein apart from the grade of tumor differentiation was an independent prognostic factors for the survival of patients with colon adenocarcinoma. Studies analyzing Grx2 levels in patients' blood confirmed that the highest levels of serum Grx2 protein was also found in stage I patients, which was reflected in the survival curves. A higher level of Grx2 in the serum has been associated with a more favorable outcome. These results were supported by in vitro analysis conducted on colorectal cancer cell lines that corresponded to stages I, II, and III of colorectal cancer, using qRT-PCR and Western Blot.

Colorectal cancer (CRC) is one of the most frequent types of cancer, with high incidence rates and mortality globally. The extended timeframe for developing CRC allows for the potential screening and early identification of the disease. Furthermore, studies have shown that survival rates for patients with cancer are increased when diagnoses are made at earlier stages. Recent research suggests that the development of CRC, including its precancerous lesion, is influenced not only by genetic factors but also by epigenetic variables. Studies suggest epigenetics plays a significant role in cancer development, particularly CRC. While this approach is still in its early stages and faces challenges due to the variability of CRC, it shows promise as a potential method for understanding and addressing the disease. This review examined the current evidence supporting genetic and epigenetic biomarkers for screening and diagnosis. In addition, we also discussed the feasibility of translating these methodologies into clinical settings. Several markers show promising potential, including the methylation of vimentin (VIM), syndecan-2 (SDC2), and septin 9 (SEPT9). However, their application as screening and diagnostic tools, particularly for early-stage CRC, has not been fully optimized, and their effectiveness needs validation in large, multi-center patient populations. Extensive trials and further investigation are required to translate genetic and epigenetic biomarkers into practical clinical use. biomarkers, diagnostic biomarkers.

We aimed to explore the prognostic value of Septin9 DNA methylation in breast cancer.

Breast cancer patients with and without recurrence or metastasis and matched non-breast cancer patients were screened retrospectively from 2014 to 2016. Bisulfite conversion and fluorescence quantitative methylation-specific polymerase chain reaction were used to detect the Septin9 methylation status and distribution levels in patient breast tissues.

Septin9 DNA methylation was more frequent in breast cancer tissues than in non-breast cancer tissues, but was not significantly correlated with any relevant breast cancer patient clinicopathological characteristic. Septin9 methylation rates were higher in patients with recurrence or metastasis. Septin9 methylation, tumor size, lymph node status, and progesterone receptor (PR) expression could influence prognosis. Septin9 methylation was significantly associated with worse disease-free survival in breast cancer patients, with receiver operating characteristic curve analysis indicating that it had good prognostic ability, with an area under the curve (AUC) value of 0.719. The AUC values increased when Septin9 methylation was combined with tumor size, lymph node status, and PR to predict prognosis.

Septin9 DNA methylation was an independent predictors of breast cancer prognostic risk. This could possibly help improve comprehensive prognosis prediction methods when combined with other risk factors.

CRC is a major global health concern and is responsible for a significant number of cancer-related deaths each year. The successful treatment of CRC becomes more difficult when it goes undetected until it has advanced to a later stage. Diagnostic biomarkers can play a critical role in the early detection of CRC, which leads to improved patient outcomes and increased survival rates. It is important to develop reliable biomarkers for the early detection of CRC to enable timely diagnosis and treatment. To date, CRC detection methods such as endoscopy, blood, and stool tests are imperfect and often only identify cases in the later stages of the disease. To overcome these limitations, researchers are turning to molecular biomarkers as a promising avenue for improving CRC detection. Diagnostic information can be provided more reliably through a noninvasive approach using biomarkers such as mRNA, circulating cell-free DNA, micro-RNA, long non-coding RNA, and proteins. These biomarkers can be found in blood, tissue, feces, and volatile organic compounds. The identification of molecular biomarkers with high sensitivity and specificity for early detection of CRC that are safe, cost-effective, and easily measurable remains a significant challenge for researchers. In this article, we will explore the latest advancements in blood-based diagnostic biomarkers for CRC and their potential impact on improving patient survival rates.

Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In recent years, the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques, and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality, and survival rate for CRC.

Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.Impact statementWhat is already known on this subject? The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction.What the results of this study add? Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg.What the implications are of these findings for clinical practice and/or further research? This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.

Colorectal carcinoma (CRC) is the third most common cancer in terms of diagnosis and the second in terms of mortality. Recent studies have shown that various proteins, extracellular vesicles (i.e., exosomes), specific genetic variants, gene transcripts, cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and altered epigenetic patterns, can be used to detect, and assess the prognosis of CRC. Over the last decade, a plethora of conventional methodologies (e.g., polymerase chain reaction [PCR], direct sequencing, enzyme-linked immunosorbent assay [ELISA], microarray, in situ hybridization) as well as advanced analytical methodologies (e.g., microfluidics, electrochemical biosensors, surface-enhanced Raman spectroscopy [SERS]) have been developed for analyzing genetic and epigenetic biomarkers using both optical and non-optical tools. Despite these methodologies, no gold standard detection method has yet been implemented that can analyze CRC with high specificity and sensitivity in an inexpensive, simple, and time-efficient manner. Moreover, until now, no study has critically reviewed the advantages and limitations of these methodologies. Here, an overview of the most used genetic and epigenetic biomarkers for CRC and their detection methods are discussed. Furthermore, a summary of the major biological, technical, and clinical challenges and advantages/limitations of existing techniques is also presented.

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.

It is worth noting the limitations in sensitivity of the existing biomarkers carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in detection of colorectal cancer (CRC). In our study, we address the performance of the liquid biopsy biomarker "methylated septin 9" (mSEPT9) in the detection and disease surveillance of CRC.

The monocentric prospective survey encompassed 120 patients diagnosed with CRC who underwent planned curative resection between December 2018 and December 2020. Blood samples were collected from the participants preoperatively as well as at 7 days, 6 weeks, and 3 months postoperatively. The presence of mSEPT9, CEA, and CA 19-9 was detected using the pro Epi Colon® 2.0 CE test, Elecsys® CEA, and Elecsys® CA19-9 electrochemiluminescence immunoassay, respectively.

In the preoperative setting, mSEPT9 demonstrated superior capability in identifying patients with CRC compared to CEA and CA 19-9, with detection rates of 57%, 32%, and 18% respectively. Combining all three biomarkers increased the overall sensitivity to 66% preoperatively. In considering UICC stage and T-status, mSEPT9 exhibited higher sensitivity across all stages in comparison with conventional tumor markers, and 65% of patients with metastases were identified postoperatively through mSEPT9. Tumor recognition after surgery was achieved with the sensitivity of 72% and specificity of 91%.

We recommend using mSEPT9 as a non-invasive diagnostic tool for the ongoing monitoring of patients with CRC. The sensitivity and specificity exhibited by mSEPT9 in recognition of tumor after surgery, highlights its particular potential for monitoring of CRC patients.

We evaluate the prognostic value of chemotherapy and other prognostic factors on overall survival among colon patients with deficient mismatch repair (dMMR), and determine the optimum time to start chemotherapy after surgery. Data of 306 colon cancer patients with dMMR who received radical surgery were collected from three Chinese centers between August 2012 and January 2018. Overall survival (OS) was assessed with the Kaplan-Meier method and log-rank. Cox regression analysis were used to assess influencing prognosis factors. The median follow-up time for all patients was 45.0 months (range, 1.0-100). There was a nonsignificant OS benefit from chemotherapy for patients with stage I and stage II disease, including high-risk stage II disease (log-rank p: 0.386, 0.779, 0.921), and a significant OS benefit for patients with stage III and stage IV disease for receiving post-operation chemotherapy (log-rank p = 0.002, 0.019). Stage III patients benefitted from chemotherapy regimens that contained oxaliplatin (log-rank p = 0.004), and Starting chemotherapy with oxaliplatin treatment earlier resulted in better outcomes (95% CI 0.013-0.857; p = 0.035). Chemotherapy regimens containing oxaliplatin can prolong the survival time of stage III and IV dMMR colon cancer patients. This beneficial manifestation was more pronounced after starting chemotherapy treatment early post operation. High risk stage II dMMR colon patients including T₄N₀M₀ cannot benefit from chemotherapy.

The oncogenic effects of long non-coding RNA (lncRNA) Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) role in colorectal cancer (CRC) hasn't been sufficiently inspected in relation to the Homo sapiens (hsa)-microRNA (miR)- 485-5p/ heat shock protein 90 (HSP90) axis, clinically. qRT-PCR was performed to detect lncRNA NNT-AS1 and hsa-miR-485-5p expression levels in 60 Egyptian patients' sera. HSP90 serum level was quantified using Enzyme-linked immunosorbent assay (ELISA). The relative expression level of the studied non-coding RNAs as well as the HSP90 ELISA concentration were correlated with patients clinicopathological characteristics and correlated to each other. The axis diagnostic utility in comparison with carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) tumor markers (TMs) was studied by receiver operating characteristic (ROC) curve analysis. The relative lncRNA NNT-AS1 expression level fold change 56.7 (13.5-112) and HSP90 protein ELISA level 6.68 (5.14-8.77) (ng/mL) were elevated, while, for hsa-miR-485-5p 0.0474 (0.0236-0.135) expression fold change was repressed in CRC Egyptian patients' cohort sera, being compared to 28 apparently healthy control subjects. LncRNA NNT-AS1 specificity is 96.4% and a sensitivity of 91.7%, hsa-miR-485-5p showed 96.4% specificity, 90% sensitivity, and for HSP90 89.3%, 70% specificity and sensitivity, respectively. Those specificities and sensitivities were superior to the classical CRC TMs. A significant negative correlation was found between hsa-miR-485-5p with lncRNA NNT-AS1 (r = -0.933) expression fold change or with HSP90 protein blood level (r = -0.997), but, significant positive correlation was there between lncRNA NNT-AS1 and HSP90 (r = 0.927). LncRNA NNT-AS1/hsa-miR-485-5p/HSP90 axis could be a prospect for CRC development as well as diagnosis. Being correlated and related to CRC histologic grades 1-3, therefore, lncRNA NNT-AS1/hsa-miR-485-5p/HSP90 axis (not individually) expression approved clinically and in silico, could aid treatment precision.

Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early detection and intervention can effectively improve the survival rate and quality of life. Although colonoscopy can detect and diagnose CRC, it is unsuitable for CRC screening in average-risk populations. Some commercial kits based on DNA mutation or methylation are approved for screening, but the low sensitivity for advanced adenoma or early-stage CRC would limit the applications.

Recently, researchers have focused on developing noninvasive or minimally invasive, easily accessible biomarkers with higher sensitivity and accuracy for CRC screening. Numerous reports describe advances in biomarkers, including DNA mutations and methylation, mRNA and miRNA, gut microbes, and metabolites, as well as low-throughput multiomics panels. In small cohorts, the specificity and sensitivity improved when fecal immunochemical testing combined with other biomarkers; further verification in large cohorts is expected. In addition, the continuous improvement of laboratory technology has also improved the sensitivity of detection technology, such as PCR, and the application of CRISPR/Cas technology. Besides, artificial intelligence has extensively promoted the mining of biomarkers. Machine learning was performed to construct a diagnosis model for CRC screening based on the cfDNA fragment features from whole-genome sequencing data. In another study, multiomics markers, including cfDNA, epigenetic, and protein signals, were also discovered by machine learning. Finally, advancements in sensor technology promote the applicability of volatile organic compounds in CRC early detection.

Here, the authors review advances in early detection and screening of CRC based on different biomarker types. Most studies reported optimistic findings based on preliminary research, and prospective clinical studies are ongoing. These promising biomarkers are expected to more accurately identify early-stage patients with CRC and be applied in the future.

For stage III colorectal cancer (CRC) patients with a high risk of recurrence, intensified adjuvant chemotherapy can improve overall survival. We aimed to develop a circulating tumor DNA (ctDNA) methylation marker model for predicting the relapse risk of stage III CRC patients. Differentially methylated markers identified between 53 normal mucosa samples and 165 CRC tissue samples, as well as between plasma samples from 75 stage I/II (early-stage) CRC patients and 55 stage IV (late-stage) CRC patients, were analyzed using Student's t-tests. The overlapping methylation markers shared by plasma and tissue samples were used to establish a methylation marker model to evaluate the tumor burden in the peripheral blood of CRC patients using the random forest method. This model was verified in the validation cohort (n = 44) and then applied to predict recurrence risk in 50 stage III CRC patients and monitor the clinical disease course in serial samples from four CRC patients. We built a five-marker-based ctDNA methylation model that had high sensitivity (84.21%) and specificity (84%) in identifying late-stage CRC in a validation cohort containing 24 stage I/II CRC patients and 20 stage IV CRC patients. The model achieved high sensitivity (87.5%) and specificity (94.12%) in predicting tumor relapse in an independent cohort of 50 stage III CRC patients and could be an independent recurrence risk factor for stage III patients [Hazard ratio (HR), 60.4; 95% confidence interval (CI): 7.68-397; p = 9.73e-5]. Analysis of serial blood samples of CRC showed that the model could monitor disease relapse earlier than imaging examination and serum carcinoembryonic antigen (CEA) and so may provide an opportunity for the early adjustment of therapeutic strategies. Moreover, the model could potentially monitor the clinical course and treatment response dynamically. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Colorectal cancer (CRC) became the third most commonly diagnosed malignancy and the second leading cause of cancer death in 2020. However, the rates of early screening and early diagnosis for CRC remain unsatisfactory. Thus, it is essential to explore the initiating factors of CRC and strategies for its early diagnosis. Research progress in liquid biopsy has led to the finding that circulating tumor-derived DNA (ctDNA) and exosomes play vital roles in early detection of CRC. THE APPLICATIONS OF LIQUID BIOPSY FOR EARLY DETECTION OF COLORECTAL CANCER: Moreover, the increased understanding of epigenetics has highlighted the role of ctDNA methylation in CRC carcinogenesis, and the detection of aberrant ctDNA methylation markers is a feasible strategy for diagnosis of early-stage CRC. Among exosomal markers, microRNAs (miRNAs) are abundant and are the most researched. Upregulated or downregulated expression of exosome-derived miRNAs can indicate the occurrence of early-stage CRC.

The current research progress on aberrant ctDNA methylation and tumor exosomal miRNA biomarkers in early detection of CRC is summarized in this review, and the advantages and shortcomings of the methods are discussed.

Although colorectal cancer (CRC) is easy to treat surgically and can be combined with postoperative chemotherapy, its five-year survival rate is still not optimistic. Therefore, developing sensitive, efficient, and compliant detection technology is essential to diagnose CRC at an early stage, providing more opportunities for effective treatment and intervention. Currently, the widely used clinical CRC detection methods include endoscopy, stool examination, imaging modalities, and tumor biomarker detection; among them, blood biomarkers, a noninvasive strategy for CRC screening, have shown significant potential for early diagnosis, prediction, prognosis, and staging of cancer. As shown by recent studies, electrochemical biosensors have attracted extensive attention for the detection of blood biomarkers because of their advantages of being cost-effective and having sound sensitivity, good versatility, high selectivity, and a fast response. Among these, nano-conductive polymer materials, especially the conductive polymer polypyrrole (PPy), have been broadly applied to improve sensing performance due to their excellent electrical properties and the flexibility of their surface properties, as well as their easy preparation and functionalization and good biocompatibility. This review mainly discusses the characteristics of PPy-based biosensors, their synthetic methods, and their application for the detection of CRC biomarkers. Finally, the opportunities and challenges related to the use of PPy-based sensors for diagnosing CRC are also discussed.

Methylated syndecan2 (mSDC2) in stool samples has been found to be associated with colorectal cancer (CRC) and precancerous lesions. However, the available data are limited, and no previous studies have compared the analysis of mSDC2 with other diagnostic tests. Thus, we aimed to evaluate the clinical performance of a stool mSDC2 test and compare its performance with that of blood-based tests for methylated septin9 (mSEPT9), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 724 (CA724) in detecting colorectal neoplasms.

The gold standard diagnostic technique that was used was colonoscopy combined with a pathological analysis of biopsied tissue. Stool DNA was extracted from 1,002 stool samples (445 from CRCs, 115 from adenomas, and 442 from controls) and then bisulfite-converted, followed by real-time quantitative methylation-specific polymerase chain reaction. Blood mSEPT9 levels were quantified by the Epi proColon 2.0 assay, and serum CEA, CA19-9 and CA724 levels were measured by electrochemiluminescence. The main indexes used during the evaluation were sensitivity, specificity and the area under the receiver operating characteristic curve (AUC).

Stool mSDC2 detected 69.7% of CRCs, which was significantly higher than 53.8% by plasma mSEPT9, 37.2% by CEA, 13.1% by CA19-9 and 17.5% by CA724; for adenoma, the detection rates were 31.3%, 11.1%, 2.3% and 11.9%, respectively. The AUC of mSDC2 in detecting CRC was 0.83, compared to 0.72, 0.75, 0.63 and 0.54 for mSEPT9, CEA, CA19-9 and CA724, respectively. mSDC2 identified patients with stage I-III CRC with a sensitivity of 71.6%, which was significantly higher than that of mSEPT9, CEA, CA19-9 and CA724 (54.2%, 35.5%, 11.9%, and 15.0%, respectively); for stage IV CRC, the sensitivities of mSDC2, mSEPT9, CEA, CA19-9 and CA724 were 75.9%, 82.6%, 79.3%, 36.0% and 56.5%, respectively. SDC2 and CEA had a significantly higher sensitivity for distal CRC than for proximal CRC.

The stool SDC2 methylation test had a better performance in detecting nonmetastatic CRC and adenoma than evaluations of mSEPT9, CEA, CA19-9 and CA724 in blood. Our findings could be used to modify approaches for CRC prevention and early detection.