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Abstract Background More than 90% of colorectal cancer (CRC) arises from advanced adenomas (AA) and gut microbes are closely associated with the initiation and progression of both AA and CRC. Objective To analyze the characteristic microbes in AA. Methods Fecal samples were collected from 92 AA and 184 negative control (NC). Illumina HiSeq X sequencing platform was used for high-throughput sequencing of microbial populations. The sequencing results were annotated and compared with NCBI RefSeq database to find the microbial characteristics of AA. R-vegan package was used to analyze α diversity and β diversity. α diversity included box diagram, and β diversity included Principal Component Analysis (PCA), principal co-ordinates analysis (PCoA), and non-metric multidimensional scaling (NMDS). The AA risk prediction models were constructed based on six kinds of machine learning algorithms. In addition, unsupervised clustering methods were used to classify bacteria and viruses. Finally, the characteristics of bacteria and viruses in different subtypes were analyzed. Results The abundance of Prevotella sp900557255, Alistipes putredinis, and Megamonas funiformis were higher in AA, while the abundance of Lilyvirus, Felixounavirus, and Drulisvirus were also higher in AA. The Catboost based model for predicting the risk of AA has the highest accuracy (bacteria test set: 87.27%; virus test set: 83.33%). In addition, 4 subtypes (B1V1, B1V2, B2V1, and B2V2) were distinguished based on the abundance of gut bacteria and enteroviruses (EVs). Escherichia coli D, Prevotella sp900557255, CAG-180 sp000432435, Phocaeicola plebeiuA, Teseptimavirus, Svunavirus, Felixounavirus, and Jiaodavirus are the characteristic bacteria and viruses of 4 subtypes. The results of Catboost model indicated that the accuracy of prediction improved after incorporating subtypes. The accuracy of discovery sets was 100%, 96.34%, 100%, and 98.46% in 4 subtypes, respectively. Conclusion Prevotella sp900557255 and Felixounavirus have high value in early warning of AA. As promising non-invasive biomarkers, gut microbes can become potential diagnostic targets for AA, and the accuracy of predicting AA can be improved by typing.

Background: More than 90% of colorectal cancer (CRC) arises from advanced adenomas (AA) and gut microbes are closely associated with the initiation and progression of both AA and CRC. Objective: To analyze the characteristic microbes in AA. Methods: Fecal samples were collected from 92 AA and 184 negative control (NC). Illumina HiSeq X sequencing platform was used for high-throughput sequencing of microbial populations. The sequencing results were annotated and compared with NCBI RefSeq database to find the microbial characteristics of AA. R-vegan package was used to analyze α diversity and β diversity. α diversity included box diagram, and β diversity included Principal Component Analysis (PCA), principal co-ordinates analysis (PCoA), and non-metric multidimensional scaling (NMDS). The AA risk prediction models were constructed based on six kinds of machine learning algorithms. In addition, unsupervised clustering methods were used to classify bacteria and viruses. Finally, the characteristics of bacteria and viruses in different subtypes were analyzed. Results: The abundance of Prevotella sp900557255, Alistipes putredinis, and Megamonas funiformis were higher in AA, while the abundance of Lilyvirus, Felixounavirus, and Drulisvirus were also higher in AA. The Catboost based model for predicting the risk of AA has the highest accuracy (bacteria test set: 87.27%; virus test set: 83.33%). In addition, 4 subtypes (B1V1, B1V2, B2V1, and B2V2) were distinguished based on the abundance of gut bacteria and enteroviruses (EVs). Escherichia coli D, Prevotella sp900557255, CAG-180 sp000432435, Phocaeicola plebeiuA, Teseptimavirus, Svunavirus, Felixounavirus, and Jiaodavirus are the characteristic bacteria and viruses of 4 subtypes. The results of Catboost model indicated that the accuracy of prediction improved after incorporating subtypes. The accuracy of discovery sets was 100%, 96.34%, 100%, and 98.46% in 4 subtypes, respectively. Conclusion: Prevotella sp900557255 and Felixounavirus have high value in early warning of AA. As promising non-invasive biomarkers, gut microbes can become potential diagnostic targets for AA, and the accuracy of predicting AA can be improved by typing. Highlights: The bacteria (including Prevotella sp900557255, Alistipes putredinis, Megamonas funiformis, etc.) and viruses (including Lilyvirus, Felixounavirus, and Drulisvirus, etc.) existed differences in AA. And there were correlations between AA and basic information, lipid index and serological index. Prediction models based on bacteria and viruses were established to distinguish AA, and the accuracy reached 87.27% and 83.33%. A new typing method was established based on bacteria and viruses to divide gut microbes into 4 subtypes. Prediction models after typing had higher accuracy (100% in B1V1, 96.34% in B1V2, 100% in B2V1, 98.46% in B2V2). [ABSTRACT FROM AUTHOR]

Abstract Background Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicenter cohort of 433 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC. Results First, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new noninvasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test. Conclusions Overall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC.

Background: Miss rate of colorectal neoplasia is associated with lesion histology, size, morphology, or location. Objectives: We aim to compare the efficacy of Linked color imaging (LCI) versus white light imaging (WLI) for adenoma detection rate (ADR), the detection of sessile serrated lesions (SSLs), serrated lesions (SLs), advanced adenomas (AAs), diminutive lesions (DLs), and flat lesions (FLs) by using per-patient and per-lesion analysis based on randomized controlled trials (RCTs). Design: Systematic review and meta-analysis. Data sources and methods: PubMed, Embase, and Cochrane databases were searched through May 1st, 2023. We calculated risk ratio for dichotomous outcomes and mean difference for continuous outcomes, and performed sensitivity analyses and subgroup analyses. Results: Overall, 17 RCTs (10,624 patients) were included. In per-patient analysis, ADR was higher in the LCI group versus the WLI group (p < 0.00001). This effect was consistent for SSL (p = 0.005), SLs (p = 0.01), AAs (p = 0.04), DLs (p < 0.00001), and FLs (p < 0.0001). In per-lesion analysis, LCI showed a significant superiority over WLI with regard to the mean number of adenomas per patient (p < 0.00001). This effect was in accordance with mean SSL (p = 0.001), mean SLs (p < 0.00001), and mean DLs (p < 0.0001) per patient. A subgroup analysis showed that the beneficial effect of the LCI group on the detection of AAs, SSL, and FLs was maintained only for studies when experts and trainees were included but not for experts only. Conclusions: Meta-analyses of RCTs data support the use of LCI in clinical practice, especially for trainees. [ABSTRACT FROM AUTHOR]

Background: Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicenter cohort of 433 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC. Results: First, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new noninvasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test. Conclusions: Overall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC. [ABSTRACT FROM AUTHOR]

Background: The Al-Kharj colorectal cancer (CRC) screening program was implemented for five years (2017-2022) in a central urban area of Riyadh Province, Saudi Arabia, to assess the participation and impact of the program in average-risk individuals. Methods: The high sensitivity-guaiac based-fecal occult blood test (HSgFOBT) was used as a first-line investigation to identify asymptomatic patients, aged 45–75 years, requiring CRC screening using colonoscopy. The program was run in three tertiary hospitals in the area. Results: The five-year participation rate was 73% (35,640/48,897). The average age was 53 years (range 45–75), 49% were female (17,464/35,640), all were asymptomatic, and 77% had adequate bowel preparation. The HSgFOBT (+) rate was 6.3% (n = 2245), and 76% (n = 1701) of these underwent colonoscopy. The prevalence of findings were as follows: CRC, 4.8% (81/1701); advanced adenoma, 9.5% (162/1701); adenoma, 15.9% (270/1701); non-adenomatous polyps, 7.9% (135/1701); and no polyps or tumors, 25.4% (432/1701). Among participants aged 45–50 years, early onset-CRC had female predominance, while those ≥50 years with late onset-CRC were predominantly male. CRC was more prevalent in the left colon (P < 0.005). Conclusions: Approximately one-third of the participants diagnosed with CRC had early-onset CRC. Screening participation was desirable for the defined target population. Public education is necessary along with expanded colonoscopy resources to continue further citizen participation.

Background: The Al-Kharj colorectal cancer (CRC) screening program was implemented for five years (2017- 2022) in a central urban area of Riyadh Province, Saudi Arabia, to assess the participation and impact of the program in average-risk individuals. Methods: The high sensitivity-guaiac based-fecal occult blood test (HSgFOBT) was used as a first-line investigation to identify asymptomatic patients, aged 45-75 years, requiring CRC screening using colonoscopy. The program was run in three tertiary hospitals in the area. Results: The five-year participation rate was 73% (35,640/48,897). The average age was 53 years (range 45-75), 49% were female (17,464/35,640), all were asymptomatic, and 77% had adequate bowel preparation. The HSgFOBT (+) rate was 6.3% (n = 2245), and 76% (n = 1701) of these underwent colonoscopy. The prevalence of findings were as follows: CRC, 4.8% (81/1701); advanced adenoma, 9.5% (162/1701); adenoma, 15.9% (270/1701); non-adenomatous polyps, 7.9% (135/1701); and no polyps or tumors, 25.4% (432/1701). Among participants aged 45-50 years, early onset-CRC had female predominance, while those ≥50 years with late onset-CRC were predominantly male. CRC was more prevalent in the left colon (P < 0.005). Conclusions: Approximately one-third of the participants diagnosed with CRC had early-onset CRC. Screening participation was desirable for the defined target population. Public education is necessary along with expanded colonoscopy resources to continue further citizen participation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) develops mainly from colorectal advanced adenomas (AA), which are considered precancerous lesions. Novel early diagnostic biomarkers are urgently needed to distinguish CRC and AA from healthy control (HC). Alternative glycosylation of serum IgG has been shown to be closely associated with CRC. We aimed to explore the potential of IgG N‐glycan as biomarkers in the early differential diagnosis of CRC. The study population was strictly matched to the exclusion criteria process. Serum IgG N‐glycan profiles were analyzed by a robust and reliable relative quantitative method based on ultra‐performance liquid chromatography (UPLC). Relative quantification and classification performance of IgG N‐glycans were evaluated by Mann‐Whitney U tests and ROC curve based on directly detected and derived glycan traits, respectively. Six and 14 directly detected glycan traits were significantly changed in AA and CRC, respectively, compared with HC. GP1 and GP3 were able to accurately distinguish AA from HC for early precancerous lesions screening. GP4 and GP14 provided a high value in discriminating CRC from HC. A novel combined index named GlycoF, including GP1, GP3, GP4, GP14 and CEA was developed to provide a potential early diagnostic biomarker in discriminating simultaneously AA (AUC = 0.847) and CRC (AUC = 0.844) from HC. GlycoF also demonstrated a superior CRC detection rate across CRC all stages and conspicuous prediction ability of risk of relapse. Serum IgG N‐glycans analysis provided powerful early screening biomarkers that can efficiently differentiate CRC and AA from HC. [ABSTRACT FROM AUTHOR]

Background: Miss rate of colorectal neoplasia is associated with lesion histology, size, morphology, or location. Objectives: We aim to compare the efficacy of Linked color imaging (LCI) versus white light imaging (WLI) for adenoma detection rate (ADR), the detection of sessile serrated lesions (SSLs), serrated lesions (SLs), advanced adenomas (AAs), diminutive lesions (DLs), and flat lesions (FLs) by using per-patient and per-lesion analysis based on randomized controlled trials (RCTs). Design: Systematic review and meta-analysis. Data sources and methods: PubMed, Embase, and Cochrane databases were searched through May 1st, 2023. We calculated risk ratio for dichotomous outcomes and mean difference for continuous outcomes, and performed sensitivity analyses and subgroup analyses. Results: Overall, 17 RCTs (10,624 patients) were included. In per-patient analysis, ADR was higher in the LCI group versus the WLI group (푝 < 0.00001). This effect was consistent for SSL (푝 = 0.005), SLs (푝 = 0.01), AAs (푝 = 0.04), DLs (푝 < 0.00001), and FLs (푝 < 0.0001). In per-lesion analysis, LCI showed a significant superiority over WLI with regard to the mean number of adenomas per patient (푝 < 0.00001). This effect was in accordance with mean SSL (푝 = 0.001), mean SLs (푝 < 0.00001), and mean DLs (푝 < 0.0001) per patient. A subgroup analysis showed that the beneficial effect of the LCI group on the detection of AAs, SSL, and FLs was maintained only for studies when experts and trainees were included but not for experts only. Conclusions: Meta-analyses of RCTs data support the use of LCI in clinical practice, especially for trainees. [ABSTRACT FROM AUTHOR]

Background: Stool-based molecular markers have shown potential as a strategy for colorectal cancer (CRC) screening. This study aimed to evaluate the feasibility of using microRNA-92a expression as a biomarker for CRC in stool samples. Methods: The level of microRNA-92a was measured in stool samples from 210 CRC patients, 29 patients with advanced adenomas, 15 patients with other cancers, and 101 healthy controls, using real-time quantitative polymerase chain reaction. Receiver operating characteristic curves were used to evaluate sensitivity and specificity. Results: MicroRNA-92a expression was positive in 70.1% of CRC patients, 44.8% of advanced adenomas patients, and 36.6% of healthy controls, using a cut-off value of 31.5. The corresponding sensitivity and specificity for discriminating CRC from advanced adenomas were 66.9% and 63.4%, respectively. Moreover, stool-based microRNA-92a expression was better at detecting CRC cancers in the distal colon (sensitivity 82.1%) than the proximal colon (sensitivity 67.9%). There were no significant differences in clinical stage of CRC when comparing AUCs of each parameter (P > 0.05). Conclusion: These findings suggest that microRNA-92a expression in stool samples could serve as a promising non-invasive biomarker for CRC detection. [ABSTRACT FROM AUTHOR]

Simple Summary: Many countries have implemented, or are implementing, general age-based screening programs to reduce mortality due to colorectal cancer. Fecal hemoglobin immunodetection (FIT) in combination with endoscopy has already been relatively successful in achieving this goal. However, there are issues that can be improved in relation to participation rates and reduction in false positives. We studied whether the blood biomarker soluble-CD26 (sCD26), a glycoprotein with dipeptidyl peptidase enzyme activity (DPP4), could help in the early diagnosis of colorectal cancer and advanced adenomas in combination with FIT, also reducing false positives. We propose a sequential testing strategy for FIT positive individuals, offering an alternative blood test with our biomarker for a confirmation prior to colonoscopy in the short term. Fecal hemoglobin immunodetection (FIT) in combination with endoscopy has been implemented to reduce mortality from colorectal cancer (CRC), although there are issues that can be improved in relation to participation rates. We studied whether the blood biomarker soluble-CD26 (sCD26), related at least in part to the immune system and inflammation, and/or its dipeptidyl peptidase enzyme activity (DPP4), could help reduce false positives. In a cohort of 1703 individuals who underwent colonoscopy and had a serum sample, sCD26 and DPP4 activity showed statistically significant differences regarding sex and age. According to the colonoscopy findings, sCD26 and DPP4 activity progressively decreased in advanced adenomas and CRC, with statistically significant differences, even between both groups; 918 of them had a FIT result (n = 596 positive cases) with approximately 70% of these (n = 412) false positives. With cut-offs of 440 ng/mL for sCD26, 42 mU/mL for DPP4, and 11 ng/mU for their ratio, the combined information of the three biomarkers (at least positive for one biomarker) identified almost all advanced adenomas and CRC cases in the FIT cohort with approximately half of the false positives compared to FIT. A sequential testing strategy with FIT and our blood biomarker test is proposed. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer is the second most common cause of cancer death worldwide. Aspirin, due to its antineoplastic effects, has been suggested to have chemopreventive effects on colorectal cancer based on recent trials. We conducted this systematic review and meta-analysis to provide an updated evidence about the long-term efficacy of daily aspirin use in the prevention of colorectal cancer. Methods: We searched Medline/PubMed, Ovid, Web of Science, and Cochrane Library. We included randomized controlled trials (RCTs) that compared the efficacy of daily aspirin use to placebo in healthy individuals at the time of study entry. The desired outcomes of this review were the incidence of advanced lesions (i.e., adenomas with villous component, adenomas ≥1 cm in diameter, adenomas with high-grade dysplasia, and/or invasive cancer) and colorectal adenomas. Results: A total of 15 articles representing 11 RCTs were included. Overall, the results indicated that aspirin significantly reduced the risk of developing colorectal adenomas but not advanced lesions at 3 years (risk ratio (RR) = 0.84, P < 0.05 and risk ratio = 0.82, P = 0.10, respectively). At 5 years, the risk of advanced lesions but not adenomas was reduced by aspirin (RR = 0.68, P < 0.05 and RR = 0.87, P = 0.22, respectively). Aspirin was not found to have an effect on the risk of advanced lesions or adenomas beyond 5 years (hazard ratio (HR) = 0.82, P = 0.07 and HR = 0.99, P = 0.82, respectively). Conclusion: Overall, aspirin (particularly high dose) only reduced the risk of advanced lesions up to 5 years. [ABSTRACT FROM AUTHOR]

Abstract Methylated SEPT9 showed relatively low sensitivity in detecting early stage colorectal cancer (CRC) and advanced adenomas (AA) in plasma. Combination of multiple biomarkers was an effective strategy to improve sensitivity in early stage cancer diagnosis and screening. A new qPCR‐based assay combining the detection of methylated SEPT9 and SDC2 (ColoDefense test) was used. Methylation statuses of SEPT9 and SDC2 were examined in 40 sets of cancer tissues and paired adjacent tissues, 10 adenomatous polyps and 3 hyperplastic polyps (HP). Then evaluated with 384 plasma samples, including 117 CRC patients, 23 AA patients, 78 small polyps patients, and 166 normal individuals. The limit of detection of ColoDefense was about 25 pg per reaction. Both SEPT9 and SDC2 were shown by ColoDefense to be heavily methylated in CRC tissues when compared to paired paracancerous tissues and HP (P

Abstract Objective To analyze the detection rates of colorectal cancer (CRC) and polyps by population‐based screening in Guangzhou. Methods From January 2011 to December 2015, the residents aged 30‐79 were selected for CRC screening. The residents were conducted Questionnaires and/or FOBT to assess high‐risk groups, the free colonoscopy examination was recommended, and the results were evaluated in detail. Results There were 98 927 residents involving screening, 5306 high‐risk residents identified (males 1859 and females 3447), and 4713 subjects underwent colonoscopy (males 1690 and females 3023). CRC was seen in 55 individuals (males 28 and females 27), and the detection rates in male were higher than in female (P = 0.019). And the detection rates increasing with age, for people over 60 years old, were obviously higher than those younger (x2 = 18.64, P = 0.000924). The polyps were seen in 1458 (30.94%) cases， and 1420 subjects received pathological examination (adenomas 971 and non‐adenomatous polyps 449). Advanced adenomas were seen in 462 cases (males 240 and females 222) and 509 cases of non‐advanced adenomas (males 255 and females 254). For advanced adenomas, the detection rates in male were higher than female (14.20% vs 7.34%, P = 2.64 × 10−14). For the detection rates of adenomas or advanced adenomas by age, the people over 40 years were higher than younger (20.91% vs 3.61% P = 7.87 × 10−6; 9.94% vs 2.41%, P = 0.009). Conclusions For Guangzhou residents, the detection rates of CRC and adenoma were 1.17% and 20.60%. The detection rates of CRC increasing with age, for people over 60 years old, were obviously higher than those younger. But for people over 40 years, the detection rate of adenoma and advanced adenoma was higher than younger. So for people over 40 years, the CRC screening is recommended.

Objective: Screening is an effective tool for detecting colorectal lesions in asymptomatic subjects. There is a positive correlation between fecal immunochemical test (FIT) values and the size of tumors. Despite the efficacy of screening, the detection of colorectal cancer (CRC) remains low. The primary objective was to evaluate the best FIT cutoff value for detecting advanced adenomas and CRC among individuals at average risk in a country with a high incidence and morbidity from CRC., Methods: This observational and prospective study analyzed consecutive cases in 1461 asymptomatic subjects with a positive FIT (≥ 100 ng hemoglobin [Hb]/mL) referred for colonoscopy (2012-2015) at a tertiary center in Uruguay., Results: Colorectal lesions were detected in 35.3% (516/1461) of cases, with a mean age of 62.8 ± 8.3 years. About 53.2% were men and 65.1% of the tumors were located in the left side of the colon. The size of the lesion and FIT values (p = 0.001) were positively correlated. Laterally spreading tumors predominated in the right colon (586 ng Hb/mL; 95% Confidence interval [CI] 443.4-760). One hundred and thirty-five (26%) lesions were advanced adenomas (15 ± 6.7 mm); 694.6 ng/mL; 95% CI 632.4-756.9). The highest diagnostic yield (0.5112) for advanced adenomas was at a FIT level of 400 ng Hb/mL (accuracy 88.6%). There were significant differences in FIT values early and advanced CRC (927 ng/mL; [95% CI: 637-1082] vs. 1453 [95% CI: 1352-1594; p = 0.001])., Conclusion: A FIT value of 400 ng Hb/mL was the best diagnostic yield to detect advanced adenomas and CRC. This value is useful during the COVID-19 pandemic as it allows prioritization of colonoscopy to those most at risk of significant disease, thus reducing risks to both patients and healthcare workers.

Abstract Background Short telomeres have been associated with increased risk of many cancers, particularly cancers of the gastrointestinal tract including esophagus and stomach. However, the association between telomere length (TL) and colorectal cancer and its precursors, colorectal polyps, is not clear. Methods We investigated the relationship between TL and risk of colorectal polyp subtypes in a colonoscopy-based study in western Washington. Participants were 35–79 year-old enrollees at an integrated health care system, who underwent a colonoscopy between 1998 and 2007 (n = 190), completed a self-administered questionnaire, provided blood samples, and were distinguished as having adenomas, serrated polyps, or as polyp-free controls through a standardized pathology review. Telomere length (T) relative to a single copy gene (S) was measured in circulating leukocytes from stored buffy coat samples using quantitative polymerase chain reaction. Multivariable polytomous logistic regression was used to compare case groups with polyp-free controls and other case groups; adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Results TL in the shortest tertile (T/S ratio

Abstract Background Colorectal cancer is the fourth cause of cancer-related deaths worldwide, though detection at early stages associates with good prognosis. Thus, there is a clear demand for novel non-invasive tests for the early detection of colorectal cancer and premalignant advanced adenomas, to be used in population-wide screening programs. Aberrant DNA methylation detected in liquid biopsies, such as serum circulating cell-free DNA (cfDNA), is a promising source of non-invasive biomarkers. This study aimed to assess the feasibility of using cfDNA pooled samples to identify potential serum methylation biomarkers for the detection of advanced colorectal neoplasia (colorectal cancer or advanced adenomas) using microarray-based technology. Results cfDNA was extracted from serum samples from 20 individuals with no colorectal findings, 20 patients with advanced adenomas, and 20 patients with colorectal cancer (stages I and II). Two pooled samples were prepared for each pathological group using equal amounts of cfDNA from 10 individuals, sex-, age-, and recruitment hospital-matched. We measured the methylation levels of 866,836 CpG positions across the genome using the MethylationEPIC array. Pooled serum cfDNA methylation data meets the quality requirements. The proportion of detected CpG in all pools (> 99% with detection p value

• A novel non-invasive assay contain two methylated biomarkers in a single qPCR reaction. • SpecColon test has lower cost and is much easier to perform. • Less input plasma by SpecColon test but achieved comparable sensitivity and specificity for detecting CRC and AA. Methylated SFRP2 was previously reported as a non-invasive biomarker for colorectal cancer (CRC) detection with a relatively low sensitivity for early stage CRC. The purpose of this study was to evaluate the performance of a new plasma based CRC screening assay, SpecColon test, which tested methylated SFRP2 and SDC2 simultaneously in a single qPCR reaction, in detecting CRC and advanced adenomas (AA). One milliliter plasma of 122 CRC patients, 12 AA patients, 93 patients with benign polyps, and 91 normal individuals were collected from the Affiliated Hospital of Xuzhou Medical University, and all samples were examined by SpecColon test. The sensitivities for detecting AA and CRC by methylated SFRP2 alone were 50.0% (95% CI: 22.2–77.7%) and 63.1% (95% CI: 53.9–71.5%) with a specificity of 90.1% (95% CI: 81.6–95.1%). The sensitivities by methylated SDC2 alone were 33.3% (95% CI: 11.3–64.6%) and 56.6% (95% CI: 47.3–65.4%) with a specificity of 95.6% (95% CI: 88.5–98.6%). However, when methylated SFRP2 and methylated SDC2 were combined, the sensitivities for AA and CRC detection improved to 58.3% (95% CI: 28.6–83.5%) and 76.2% (95% CI: 67.5–83.3%) with a specificity of 87.9% (95% CI: 79.0–93.5%). The positive detection rates of benign polyp group and normal control group showed no significant difference (p > 0.01), whereas AA and CRC groups had significantly higher positive detection rates than normal individual group (p < 0.001). The sensitivities for AA and early stage CRC by combined test of methylated SFRP2 and methylated SDC2, the so called SpecColon test, improved upon those by either biomarker alone without significant impact on the specificity. It has the potential to become a powerful, convenient and highly effective screening tool for early CRC screening. [ABSTRACT FROM AUTHOR]

Methylated SEPT9 showed relatively low sensitivity in detecting early stage colorectal cancer (CRC) and advanced adenomas (AA) in plasma. Combination of multiple biomarkers was an effective strategy to improve sensitivity in early stage cancer diagnosis and screening. A new qPCR‐based assay combining the detection of methylated SEPT9 and SDC2 (ColoDefense test) was used. Methylation statuses of SEPT9 and SDC2 were examined in 40 sets of cancer tissues and paired adjacent tissues, 10 adenomatous polyps and 3 hyperplastic polyps (HP). Then evaluated with 384 plasma samples, including 117 CRC patients, 23 AA patients, 78 small polyps patients, and 166 normal individuals. The limit of detection of ColoDefense was about 25 pg per reaction. Both SEPT9 and SDC2 were shown by ColoDefense to be heavily methylated in CRC tissues when compared to paired paracancerous tissues and HP (P < .01). The sensitivities for detecting AA and stage I CRC by plasma SEPT9 methylation alone were 12.1% and 65.0%, and those by plasma SDC2 methylation alone were 43.5% and 55.0%. In comparison, the sensitivities to detect AA and stage I CRC by ColoDefense improved to 47.8% and 80.0%. The overall sensitivity of ColoDefense in detecting CRC was 88.9% (95% CI: 81.4%‐93.7%) with a specificity of 92.8% (95% CI: 87.4%‐96.0%). Detection of the combinatorial biomarker of methylated SEPT9 and/or SDC2 is a powerful, convenient and highly effective strategy for early CRC screening with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Objective: To analyze the detection rates of colorectal cancer (CRC) and polyps by population‐based screening in Guangzhou. Methods: From January 2011 to December 2015, the residents aged 30‐79 were selected for CRC screening. The residents were conducted Questionnaires and/or FOBT to assess high‐risk groups, the free colonoscopy examination was recommended, and the results were evaluated in detail. Results: There were 98 927 residents involving screening, 5306 high‐risk residents identified (males 1859 and females 3447), and 4713 subjects underwent colonoscopy (males 1690 and females 3023). CRC was seen in 55 individuals (males 28 and females 27), and the detection rates in male were higher than in female (P = 0.019). And the detection rates increasing with age, for people over 60 years old, were obviously higher than those younger (x2 = 18.64, P = 0.000924). The polyps were seen in 1458 (30.94%) cases， and 1420 subjects received pathological examination (adenomas 971 and non‐adenomatous polyps 449). Advanced adenomas were seen in 462 cases (males 240 and females 222) and 509 cases of non‐advanced adenomas (males 255 and females 254). For advanced adenomas, the detection rates in male were higher than female (14.20% vs 7.34%, P = 2.64 × 10−14). For the detection rates of adenomas or advanced adenomas by age, the people over 40 years were higher than younger (20.91% vs 3.61% P = 7.87 × 10−6; 9.94% vs 2.41%, P = 0.009). Conclusions: For Guangzhou residents, the detection rates of CRC and adenoma were 1.17% and 20.60%. The detection rates of CRC increasing with age, for people over 60 years old, were obviously higher than those younger. But for people over 40 years, the detection rate of adenoma and advanced adenoma was higher than younger. So for people over 40 years, the CRC screening is recommended.There were 98 927 residents involving screening and 4713 subjects (males 1690 and females 3023) underwent colonoscopy. CRC were seen in 55 individuals (male 28, female 27), and the detection rate in male were higher than in female (28/1690, 1.66% vs 0.89%, 27/3023, P= 0.019). And the adenomas were seen in 971 cases. Advanced adenomas were seen in 462 cases (male 240, female 222) and 509 cases of non‐advanced adenomas (male 255, female 254). For advanced adenomas, the detection rates in male were higher than female (14.20% vs 7.34%, P = 2.64 × 10−14). For the detection rates of adenomas or advanced adenomas by age, the people over 40 years were higher than younger (20.91% vs 3.61%, P = 7.87 × 10−6; 9.94% vs 2.41%, P = 0.009). [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia—AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35–47% AA (specificity 98–95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals.

Objective To analyze the expression of cyclooxygenase-2 (COX-2) in the patients with snow-white sign of advanced colorectal adenoma (ACA) and explore its clinical significance.Method Western blotting was employed to determine the expression of COX-2 in the adenoma tissue and the normal tissue adjacent to the adenoma tissue (>5 cm away from the distal end of the adenoma tissue) of 40 ACA patients with snow-white sign and 40 ACA patients without snow-white sign.Results The appearance of snow-white sign in ACA patients was associated with patient age ( P =0.001) and not associated with sex,smoking history,drinking history,ethnic groups,family history of colorectal cancer,abdominal pain,diarrhea,constipation,fecal occult blood,or tumor markers (all P >0.05).Snow-white sign mainly appeared in the ACA patients with multiple adenomas ( P =0.004),large adenomas ( P =0.006),adenomas in distal colon ( P =0.015),protruding polyps ( P =0.044),and late-stage pathology ( P =0.010).The occurrence of snow-white sign showed no difference in the ACA patients with different results of Japan NBI Expert Team classification ( P =0.502).The expression of COX-2 in the adenoma tissue was higher than that in the adjacent normal tissue in the patients with and without snow-white sign ( P <0.001, P =0.004).The patients with snow-white sign had higher expression of COX-2 protein in the adenoma tissue than the patients without snow-white sign ( P =0.001).The expression of COX-2 protein in the adjacent healthy tissue had no significant difference between the patients with and without snow-white sign ( P =0.603).Conclusions Snow-white sign is more like to appear in the ACA patients with young age,multiple and large adenomas,adenomas in distal colon,protruding polyps,and late-stage pathology.Moreover,the expression of COX-2 in the ACA patients with snow-white sign is significantly higher than that in the ACA patients without snow-white sign.The adults with snow-white sign are prone to cancerization than those without snow-white sign.

Purpose: Patients with a history of advanced adenomas are at increased risk of developing colorectal cancer (CRC), yet rates of adherence to current surveillance colonoscopy guidelines are poor. We determined rates of referral and adherence to 3-year interval surveillance colonoscopy in patients with advanced adenomas and identified modifiable factors as possible intervention targets to improve surveillance referral and adherence in these at-risk patients. Methods: We reviewed electronic medical records (EMR) of patients ( N = 103) who had pathology findings on screening colonoscopy that warranted a 3-year surveillance colonoscopy. We abstracted demographics, surveillance colonoscopy completion rate, documentation of initial pathology in the 'Problem List' of the EMR, and timing and nature of visits to a primary care physician (PCP). Results: Only 22 (21.4 %) patients had a record of surveillance colonoscopy completion. Among non-completers, 50.6 % of patients had no PCP visit within a year of their surveillance due date, 19.8 % saw a PCP and were not referred, and 29.6 % saw a PCP and were referred to either a gastroenterology consultation or a surveillance colonoscopy. Pathology found on initial screening was noted in the Problem List of 77.3 % of completers but only 33.3 % of non-completers ( p ≤ 0.001). Conclusions: Possible targets for interventions include using EMRs to improve physician communication and encouraging patients to have timely PCP visits and follow-through after colonoscopy referral. Clinical studies in this area have the potential to improve outcomes for patients by reducing CRC mortality through early detection. [ABSTRACT FROM AUTHOR]