Approach For Colorectal Cancer Screening Research Articles

Comprehensive Insight into Colorectal Cancer Metabolites and Lipids for Human Serum: A Proof-of-Concept Study.

Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths. The current endoscopic-based or stool-based diagnostic techniques are either highly invasive or lack sufficient sensitivity. Thus, there is a need for less invasive and more sensitive screening approaches. We, therefore, conducted a study on 64 human serum samples representing three different groups (adenocarcinoma, adenoma, and control) using cutting-edge GC×GC-LR/HR-TOFMS (comprehensive two-dimensional gas chromatography coupled with low/high-resolution time-of-flight mass spectrometry). We analyzed samples with two different specifically tailored sample preparation approaches for lipidomics (fatty acids) (25 μL serum) and metabolomics (50 μL serum). In-depth chemometric screening with supervised and unsupervised approaches and metabolic pathway analysis were applied to both datasets. A lipidomics study revealed that specific PUFA (ω-3) molecules are inversely associated with increased odds of CRC, while some PUFA (ω-6) analytes show a positive correlation. The metabolomics approach revealed downregulation of amino acids (alanine, glutamate, methionine, threonine, tyrosine, and valine) and myo-inositol in CRC, while 3-hydroxybutyrate levels were increased. This unique study provides comprehensive insight into molecular-level changes associated with CRC and allows for a comparison of the efficiency of two different analytical approaches for CRC screening using same serum samples and single instrumentation.

A multicenter, case-control study of a novel multi-target fecal DNA test for colorectal cancer detection.

26 Background: Globally, colorectal cancer (CRC) is the fourth most frequently occurring cancer and is the second leading cause of cancer-related deaths. Early detection and diagnosis of pre-cancer lesions and CRCs at curable stages could prevent the disease or improve patient survival. Colonoscopy, the current gold-standard approach for CRC screening, is an invasive procedure, and novel non-invasive alternatives are needed. Methods: In present study, we developed a novel multi-target fecal DNA based assay, which integrates detection of two stool DNA (sDNA) methylation markers by quantitative methylation-specific PCR (qMSP) and immunochemical fecal occult blood test. We performed a multi-center case-control study to validate the diagnostic performance of this novel multi-target assay. Thus far, we collected stool specimens from a total of 784 subjects including CRC, advanced adenoma, nonadvanced neoplasms and individuals with negative findings on colonoscopy from six sites across China. All participants underwent colonoscopy; the stool specimens were tested with the multi-target fecal DNA test as well as a quantitative FIT test (OC FIT-CHEK, Eiken) in parallel in order to perform head-to-head comparison of the test performance of both assays. Results: The multi-target fecal DNA test demonstrated a higher sensitivity (96.1%) than FIT (85.3%) for CRCs (n=204). Meanwhile, 20 of 39 (51.3%) patients with advanced adenoma tested positive by the fecal DNA test, which was remarkably superior to FIT (7 of 39 tested positive, 17.9%). Among 541 participants with nonadvanced neoplasms or negative findings on colonoscopy, the specificity of the DNA test was 86.9%, compared with a specificity of 93.1% achieved by FIT. Within the control group, the DNA test and FIT yielded a specificity of 90.5% and 94.9% respectively for individuals with negative results on colonoscopy. Conclusions: The novel multi-target fecal DNA test exhibited notably superior sensitivity for both CRC and advanced adenoma cases than the commercially quantitative FIT test, while sacrificing some specificity. Our results suggest that this novel multi-target fecal based test may be used as an effective tool for early detection and pre-screening of CRC. Prospective study will be conducted to further evaluate the clinical performance and cost-effectiveness of this assay.

Improved colorectal cancer screening by adding noninvasive serum-based biomarkers

Background Colorectal cancer (CRC) is one of the most common causes of cancer-related morbidity and mortality worldwide. The most widely used CRC diagnostic tests either noninvasive or invasive are limited by insufficient performance or patient compliance. Profiling inflammatory mediators with carcinogenic roles could aid in CRC diagnosis. We aimed to use multiplex bead assay in evaluating the utility of serum eotaxin-1, macrophage-inflammatory protein-1β (MIP-1β), granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor A (VEGF-A), and Fas ligand (FasL) as potential biomarkers in CRC. Patients and methods The study was conducted on 87 patients. Based on colonoscopy findings, patients were divided into 35 CRC and 52 nonmalignant patients (nine with colon polyp, 24 with colitis, and 19 with normal mucosa). Multiplex assay was used for measuring the studied biomarkers. Results The median values of eotaxin-1, MIP-1β, G-CSF, and VEGF-A were significantly higher in patients with CRC compared with the nonmalignant group. The area under the receiver operating characteristics curve for eotaxin-1, MIP-1β, G-CSF, and VEGF-A was 0.863. The area under the ROC for occult blood in stool was only 0.597. Moreover, significantly higher levels of G-CSF and VEGF-A were found in patients with CRC than the precancerous colon polyp group. Conclusions Serum profiling of eotaxin-1, MIP-1β, G-CSF, and VEGF-A could be used as potential biomarkers in early CRC diagnosis with better discriminatory power than stool occult blood and may increase occult blood performance, thus reducing false-positives rates and unneeded colonoscopy. Multiplexing bead technology represents a promising approach for CRC screening and diagnosis.

Novel multiplex stool-based assay for the detection of early-stage colon cancer in a Chinese population.

BACKGROUNDStool DNA (sDNA) methylation analysis is a promising, noninvasive approach for colorectal cancer screening; however, reliable biomarkers for detecting early-stage colon cancer (ECC) are lacking, particularly in the Chinese population.AIMTo identify a novel stool-based assay that can improve the effectiveness of ECC screening.METHODSA blinded case-control study was performed using archived stool samples from 125 ECC patients, and 125 control subjects with normal colonoscopy. The cohort was randomly divided into training and test sets at a 1.5:1 ratio. Targeted bisulfite sequencing (TBSeq) was conducted on five pairs of preoperative and postop-erative sDNA samples from ECC patients to identify DNA methylation biomarkers, which were validated using pyrosequencing. By logistic regression analysis, a multiplex stool-based assay was developed in the training set, and the detection performance was further assessed in the test set and combined set. The χ2 test was used to investigate the association of detection sensitivity with clinico-pathological features.RESULTSFollowing TBSeq, three hypermethylated cytosine-guanine sites were selected as biomarkers, including paired box 8, Ras-association domain family 1 and secreted frizzled-related protein 2, which differed between the groups and were involved in important cancer pathways. An sDNA panel containing the three biomarkers was constructed with a logistic model. Receiver operating characteristic (ROC) analysis revealed that this panel was superior to the fecal immunochemical test (FIT) or serum carcinoembryonic antigen for the detection of ECC. We further found that the combination of the sDNA panel with FIT could improve the screening effectiveness. In the combined set, the sensitivity, specificity and area under the ROC curve for this multiplex assay were 80.0%, 93.6% and 0.918, respectively, and the performance remained excellent in the subgroup analysis by tumor stage. In addition, the detection sensitivity did not differ with tumor site, tumor stage, histological differentiation, age or sex, but was significantly higher in T4 than in T1-3 stage tumors (P = 0.041).CONCLUSIONWe identified a novel multiplex stool-based assay combining sDNA methylation biomarkers and FIT, which could detect ECC with high sensitivity and specificity throughout the colon, showing a promising application perspective.

Practical considerations for colorectal cancer screening in older adults.

Recent guidelines recommend that colorectal cancer (CRC) screening after age 75 be considered on an individualized basis, and discourage screening for people over 85 due to competing causes of mortality. Given the heterogeneity in the health of older individuals, and lack of data within current guidelines for personalized CRC screening approaches, there remains a need for a clearer framework to inform clinical decision-making. A revision of the current approach to CRC screening in older adults is even more compelling given the improvements in CRC treatment, post-treatment survival, and increasing life expectancy in the population. In this review, we aim to examine the personalization of CRC screening cessation based on specific factors influencing life and health expectancy such as comorbidity, frailty, and cognitive status. We will also review screening modalities and endoscopic technique for minimizing risk, the risks of screening unique to older adults, and CRC treatment outcomes in older patients, in order to provide important information to aid CRC screening decisions for this age group. This review article offers a unique approach to this topic from both the gastroenterologist and geriatrician perspective by reviewing the use of specific clinical assessment tools, and addressing technical aspects of screening colonoscopy and periprocedural management to mitigate screening-related complications.

Potential roles of serum ATPase and AMPase in predicting diagnosis of colorectal cancer patients

ABSTRACT Colorectal cancer (CRC) is a common gastrointestinal cancer with high incidence and mortality rates. CRC may be associated with regulation of circulating nucleotides. This study aimed to evaluate the serum levels of nucleotide-metabolizing enzymes (ATPase and AMPase) in patients with CRC and to explore the clinical diagnostic value of these enzymes. The gene set variation analysis (GSVA) score of the ATP-adenosine signature was calculated using tumor samples from The Cancer Genome Atlas (TCGA). ATP-adenosine signaling plays a central role in CRC progression. A total of 135 subjects, including 87 patients with CRC and 48 healthy controls, were included. The serum levels of ATPase and AMPase in the CRC group were significantly higher than those in the control group (P < 0.05). Furthermore, ATP and AMP hydrolysis levels significantly increased in the advanced CRC group (P < 0.05). ATP and AMP hydrolysis was decreased by the ENTPDase inhibitors (POM-1 and ARL67156) and CD73 inhibitor (APCP). The sensitivities of ATPase and AMPase were 95.4% and 75.9%, respectively, which were higher than those of CEA (67.8%) and CA19-9 (72.4%). The specificities of ATPase and AMPase were 69.9% and 73.9%, respectively, which were higher than that of CA19-9 (47.8%). The combination of CEA, ATPase, and AMPase demonstrated high sensitivity (92.0%) and specificity (87.0%). Collectively, ATPase and AMPase activities are upregulated in CRC with considerable diagnostic significance. The combination of CEA, ATPase, and AMPase may provide a novel approach for CRC screening.

Contribution of Epithelial and Gut Microbiome Inflammatory Biomarkers to the Improvement of Colorectal Cancer Patients' Stratification.

In order to ensure that primary endpoints of clinical studies are attained, the patients’ stratification is an important aspect. Selection criteria include age, gender, and also specific biomarkers, such as inflammation scores. These criteria are not sufficient to achieve a straightforward selection, however, in case of multifactorial diseases, with unknown or partially identified mechanisms, occasionally including host factors, and the microbiome. In these cases, the efficacy of interventions is difficult to predict, and as a result, the selection of subjects is often random. Colorectal cancer (CRC) is a highly heterogeneous disease, with variable clinical features, outcomes, and response to therapy; the CRC onset and progress involves multiple sequential steps with accumulation of genetic alterations, namely, mutations, gene amplification, and epigenetic changes. The gut microbes, either eubiotic or dysbiotic, could influence the CRC evolution through a complex and versatile crosstalk with the intestinal and immune cells, permanently changing the tumor microenvironment. There have been significant advances in the development of personalized approaches for CRC screening, treatment, and potential prevention. Advances in molecular techniques bring new criteria for patients’ stratification—mutational analysis at the time of diagnosis to guide treatment, for example. Gut microbiome has emerged as the main trigger of gut mucosal homeostasis. This may impact cancer susceptibility through maintenance of the epithelial/mucus barrier and production of protective metabolites, such as short-chain fatty acids (SCFAs) via interactions with the hosts’ diet and metabolism. Microbiome dysbiosis leads to the enrichment of cancer-promoting bacterial populations, loss of protective populations or maintaining an inflammatory chronic state, all of which contribute to the development and progression of CRC. Meanwhile, variations in patient responses to anti-cancer immuno- and chemotherapies were also linked to inter-individual differences in intestine microbiomes. The authors aim to highlight the contribution of epithelial and gut microbiome inflammatory biomarkers in the improvement of CRC patients’ stratification towards a personalized approach of early diagnosis and treatment.

Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.

KCNQ5 and C9orf50 Methylation in Stool DNA for Early Detection of Colorectal Cancer.

BackgroundAberrant DNA methylation has emerged as a class of promising biomarkers for early colorectal cancer (CRC) detection, but the performance of methylated C9orf50 and methylated KCNQ5 in stool DNA has never been evaluated.MethodsMethylation specific quantitative PCR (qPCR) assays for methylated C9orf50 and methylated KCNQ5 were developed. The methylation levels of C9orf50 and KCNQ5 in 198 CRC patients, 20 advanced adenoma (AA) patients, 101 small polyp (SP) patients, and 141 no evidence of disease (NED) subjects were analyzed.ResultsThe methylation levels of both KCNQ5 and C9orf50 genes were significantly higher in CRC and AA groups than those in SP and NED groups, but showed no significant difference among different stages of CRC. The sensitivities of methylated KCNQ5 and methylated C9orf50 for CRC detection were 77.3% (95% CI: 70.7–82.8%) and 85.9% (95% CI: 80.0–90.2%) with specificities of 91.5% (95% CI: 85.3–95.3%) and 95.0% (95% CI: 89.7–97.8%), respectively. When C9orf50 and methylated KCNQ5 were combined, the clinical performance for CRC detection was similar to that of methylated C9orf50 alone.ConclusionsStool DNA based methylated C9orf50 test has the potential to become an alternative approach for CRC screening and prevention.

Association Between Age and Complications After Outpatient Colonoscopy

There are insufficient data describing the incidence and risk factors of postcolonoscopy complications in older individuals. To assess the association between older age (≥75 years) and the risk of postcolonoscopy complications. This population-based retrospective cohort study included adults (≥50 years) undergoing outpatient colonoscopy between April 2008 and September 2017, identified from Ontario administrative databases. Individuals with inflammatory bowel disease and hereditary colorectal cancer syndromes were excluded. The study population was subdivided into a colorectal cancer screening-eligible cohort (patients aged 50-74 years) and an older cohort (patients aged ≥75 years). The statistical analysis was conducted from December 2018 to September 2019. Older age (≥75 years). The primary outcome was postcolonoscopy complications, defined as the composite of hospitalization or emergency department visits in the 30-day period after the outpatient colonoscopy. Secondary outcomes included incidence of surgically treated colorectal cancer and all-cause mortality at 30 days. Independent variables associated with postcolonoscopy complications were also assessed. The study sample included 38 069 patients; the mean (SD) age was 65.2 (10.1) years, there were 19 037 women (50.0%), and 27 831 patients (73.1%) underwent a first colonoscopy. The cumulative incidence of complications was 3.4% (1310 patients) in the overall population, and it was higher in individuals aged 75 years or older (515 of 7627 patients [6.8%]) than in screening-eligible cohort (795 of 30 443 patients [2.6%]) (P < .001). Independent risk factors for postcolonoscopy complications were age 75 years or older (odds ratio [OR], 2.3; 95% CI, 2.0-2.6), anemia (OR, 1.4; 95% CI, 1.2-1.7), cardiac arrhythmia (OR, 1.7; 95% CI, 1.2-2.2), congestive heart failure (OR, 3.4; 95% CI, 2.5-4.6), hypertension (OR, 1.2; 95% CI, 1.0-1.5), chronic kidney disease (OR, 1.8; 95% CI, 1.1-3.0), liver disease (OR, 4.7; 95% CI, 3.5-6.5), smoking history (OR, 3.2; 95% CI, 2.4-4.3), and obesity (OR, 2.3; 95% CI, 1.2-4.2). The number of previous colonoscopies was associated with a lower risk of complications (OR, 0.9; 95% CI, 0.7-1.0). The incidence of surgically treated colorectal cancer was higher in the older cohort than the screening-eligible cohort (119 patients [1.6%] vs 144 patients [0.5%]; P < .001). All-cause mortality rates were 0.1% overall (39 patients) and 0.1% (19 patients) for individuals aged 50 to 74 years and 0.2% (20 patients) for those aged 75 years and older (P < .001). In this population-based cohort study of individuals living in southern Ontario, age of 75 years and older was associated with a higher risk of 30-day postprocedure complications after outpatient colonoscopy. These findings suggest that the decision to perform a colonoscopy should be carefully considered in patients older than 75 years, especially in the presence of comorbidities. Further studies are needed to better understand the benefits of invasive procedures as opposed to less invasive approaches for colorectal cancer screening and surveillance among older patients.

Allele frequencies of two MUTYH variants, Y179C, and G396D, in a direct-to-consumer genetic database.

63 Background: MUTYH-associated polyposis (MAP) is an autosomal recessive condition that accounts for about 0.3-0.7% of all colorectal cancer (CRC) cases. The two most common variants among people of Northern European descent are MUTYH Y179C (rs34612342) and G396D (rs36053993), with a carrier frequency of 1-2%. However, understanding the frequency of these variants in other populations can better inform population health approaches for CRC screening and prevention. This study assessed the frequency of these two variants in a generally unselected group of genotyped individuals who have used direct-to-consumer (DTC) genetic testing (23andMe, Inc. Sunnyvale, CA). Methods: Study participants were genotyped on Illumina genotyping arrays, which included the Y179C and G396D variants. Eligible subjects were 23andMe customers who were at least 18 years of age and who consented to participate in research. IRB approval was obtained from Ethical and Independent Review Services. Results: Out of the 3,617,279 eligible participants included in this study, the overall allele frequencies of Y179C and G396D were 0.18% and 0.51%, respectively. People of European descent had the highest frequencies (0.22% and 0.59%), while people of Ashkenazi Jewish, East Asian, and South Asian descent had the lowest frequencies ( &lt; 0.015% for both variants). The allele frequencies for people of Hispanic/Latino descent were 0.15% and 0.51%. Conclusions: This is the first description of an unselected cohort of individuals with MUTYH Y179C and G396D variants identified through DTC genetic testing. While these two variants were most common among people of European descent, they were also observed at relatively high frequency among people of Hispanic/Latino descent. These results may help guide CRC screening and prevention strategies in different ethnicities.

Analysis of volatile organic compounds released from SW480 colorectal cancer cells and the blood of tumor-bearing mice.

BackgroundVolatile organic compound (VOC) analysis provides an elegant approach for colorectal cancer screening. An organic compound with a high vapor pressure or volatility can be detected in the headspace of cancer cells or blood samples. Therefore, analyzing VOCs in the blood of rats inoculated with colorectal cancer tissue and in SW480 medium from cultured colorectal cancer cells may provide accurate results.MethodsAfter collecting venous blood from rats inoculated with cancer cells at different times, the cancer tissue was removed from the inoculated rats, and the medium was harvested from the cancer cells and cultured in the presence or absence of a chemotherapy drug of intestinal epithelial cells. We used solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) to analyze the headspace of the blood and media to evaluate the VOC profiles. Statistical analysis was conducted using principal component analysis (PCA) and orthogonal partial least-squares analysis (OP-LSDA).ResultsThe in vivo and in vitro analyses of the colorectal cancer samples revealed a variety of compounds, such as cyclohexanone, 1-hexanol, 2-ethyl-, butylated hydroxytoluene, cyclotrisiloxane, hexamethyl-, pentanoic acid, 2,2,4-trimethyl-3-hydroxy-isobutyl ester and acetone. Butylated hydroxytoluene is unique with regard to its presence during tumor growth and resection; it is also present during tumor cell growth and necrosis. Acetone showed unique trends in the in vivo experimental group.ConclusionsBy analyzing VOC fingerprints related to colorectal cancer (CRC), we found that butylated hydroxytoluene and acetone have unique signatures that may provide the basis for clinical diagnosis and disease assessment.

Comparative evaluation of colonoscopy, fecal immunochemical test, and a novel risk-adapted approach for colorectal cancer screening: preliminary baseline results of a multicentre randomised controlled trial (Target-C)

BackgroundFor colorectal cancer (CRC) screening, the use of risk prediction models to identify potential high-risk populations and implementation of appropriate risk-adapted screening may be more cost-effective than traditional screening strategies. However, evidence from randomised controlled trials is lacking. This study aimed to evaluate colonoscopy, fecal immunochemical test (FIT) and a novel risk-adapted screening approach in a large-scale multicentre randomised controlled trial in China. MethodsThis ongoing trial has been conducted in six study centres in five provinces in China since May 2018. People aged 50–74 years living in the study areas were approached to assess eligibility. Overall, 19 582 eligible participants were enrolled from May, 2018, to May, 2019. After providing signed informed consent, participants were randomly assigned to one of three screening groups, with a 1:2:2 ratio: (1) one-time colonoscopy (n=3937); (2) annual fecal immunochemical test (FIT; n=7858); and (3) annual risk-adapted screening strategy (n=7787). The risk-adapted screening strategy used an established CRC risk scoring system, the Asia-Pacific Colorectal Screening Score. Participants at high risk of CRC were referred for colonoscopy, whereas participants at low risk of CRC were referred for a FIT. Participants with positive FIT results were also referred for diagnostic colonoscopy. Information on clinical reports and epidemiological risk factors were collected and stored in a web-based data system. The primary outcome was detection rate of advanced colorectal neoplasia and secondary outcomes included rate of adherence to the study protocol, compliance rate of colonoscopy, detection rate of any neoplasm, complication rate, and the rate of mortality. A 4-year screening phase (with 1-year baseline screening and 3 years of follow-up screening) will be conducted for all participants and a subsequent 6-year active and passive follow-up phase will be implemented. Here we present the preliminary baseline screening results. This study was approved by the Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (18-013/1615) and the protocol was registered in the Chinese Clinical Trial Registry (identifier: ChiCTR1800015506). FindingsAfter we excluded 36 participants who did not meet the inclusion criteria after further evaluation, 19 546 participants were included for the primary analysis (3916 colonoscopy, 7854 FIT, and 7776 risk-adapted screening). Mean age was 60·5 (SD 6·5) years and 41·7% (8154 of 19 546) were men. No statistically significant differences for age and sex distribution were observed between the groups. Participation rates were 42·5% (1665 of 3916) for colonoscopy, 94·0% (7386 of 7854) for FIT, and 85·2% (6628 of 7776) for risk-adapted screening. Of the participants assessed to be at high risk of CRC in the risk-adapted group (18·9%, 1472 of 7776), 49·2% (724 of 1472) accepted colonoscopy screening, a significantly higher proportion than in the colonoscopy group (42·5%; p<0·05). Of participants assessed to be at low risk of CRC in the risk-adapted screening group (80·7%, 6279 of 7776), 94·0% (5904 of 6279) accepted FIT screening, similar to the rate in the FIT group (94·0%). The overall positivity rate of FIT was 14·3%, and over 85% of participants with positive FIT results undertook subsequent diagnostic colonoscopy. For the intention-to-screen analysis, detection rates for advanced colorectal neoplasms were 2·93% for colonoscopy, 1·29% for FIT and 1·83% for risk-adapted screening. The FIT and the risk-adapted screening groups had lower numbers of colonoscopies needed to detect one advanced neoplasm than the colonoscopy group (eight, ten, and 15 colonoscopies, respectively). InterpretationThis is the first large-scale population-based trial in China to compare effectiveness of three different colorectal cancer screening strategies targeting adults aged 50–74 years. For the interim analysis of the baseline screening in this trial, the FIT and the novel risk-adapted screening approach had higher participation rates than the colonoscopy screening approach, and they required fewer numbers of colonoscopies to detect one advanced neoplasm, indicating the feasibility and effectiveness of these two approaches in population-based CRC screening. The findings of this study may provide timely evidence in designing effective population-based CRC screening strategies. FundingThis study was sponsored by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2017-I2M-1-006) and the National Natural Science Foundation of China (81703309).

Clinical response and prognostic significance of serum miR-497 expression in colorectal cancer.

Colorectal cancer (CRC) is a common type of cancer around the world. Detection of microRNA (miRNA) aberration in blood samples is a novel approach for CRC screening. The purpose of this study was to explore the serum miR-497 expression pattern in CRC and examine its potential usefulness as a biomarker for CRC diagnosis and prognosis. Serum miR-497 expression was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 110 patients with CRC, 35 cases with colorectal adenoma, 54 cases with colorectal polyps, and 70 healthy individuals. The expression level of miR-497 was significantly downregulated in CRC tissues compared to the normal tissues based on the data from three independent studies GSE68204, GSE41655 and GSE35834. Compared to healthy controls, the serum miR-497 level was significantly decreased in patient with CRC or benign lesion (colorectal adenoma and polyps). Serum miR-497 level was dramatically increased in the post-operative blood samples from early stage CRC patients. Receiver-operating characteristic (ROC) analysis showed that serum miR-497 had a high sensitivity and specificity for discriminating CRC or precancerous colorectal lesion from normal controls. Moreover, low serum miR-497 expression was closely correlated with aggressive clinical features and shorter overall survival (OS). Kaplan-Meier analyses also revealed that OS was strongly associated with lymph node invasion, TNM stage and histological grade. Furthermore, univariate and multivariate analysis showed serum miR-497 was an independent prognostic factor for CRC. Collectively, serum miR-497 may serve as a promising biomarker for diagnosis and prognosis of CRC.

Assessing Levels and Correlates of Implementation of Evidence-Based Approaches for Colorectal Cancer Screening: A Cross-Sectional Study With Federally Qualified Health Centers.

Multiple evidence-based approaches (EBAs) exist to improve colorectal cancer screening in health clinics. The success of these approaches is tied to effective implementation. Therefore, the purpose of this study was to assess the implementation of EBAs for colorectal cancer screening and clinic-level correlates of implementation in federally qualified health centers (FQHCs). We conducted descriptive and cross-sectional analyses using data collected from FQHC clinics across seven states ( n = 51). A clinic representative completed electronic surveys about clinic characteristics (e.g., size, patient characteristics, and medical record system characteristics) and the implementation of Community Guide recommended EBAs (e.g., client reminders, small media, and provider assessment and feedback). We used bivariate Spearman correlations to assess clinic-level correlates with implementation outcomes. Most clinics were planning to implement, in the early implementation stages, or inconsistently implementing EBAs. No EBA was fully implemented by more than nine (17.6%) clinics. Clinic size variables were inversely related to implementation levels of one-on-one education; medical record variables were directly related to implementation levels of client and provider reminders as well as provider assessment and feedback; and rapid and timely feedback from clinic leaders was directly associated with implementation levels of four out of six EBAs. Given the varying levels of implementation, clinics need to assess current use of implementation strategies and improve effective program delivery to increase colorectal cancer screening among their patients. In addition, clinics should also consider how their characteristics may support or serve as a barrier to implementation in their respective settings.

B-cell lymphoma 2 is associated with advanced tumor grade and clinical stage, and reduced overall survival in young Chinese patients with colorectal carcinoma.

The development of biomarkers that accurately and reliably detect colorectal cancer is a promising approach for colorectal cancer screening. Therefore, the objective of the present study was to evaluate the protein expression of α-methylacyl-CoA racemase (P504S/AMACR), tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2) and Ki-67/mindbomb E3 ubiquitin protein ligase 1 (MIB-1) in a population of Chinese patients with colorectal carcinoma. Colorectal tumors with matched normal tissue margins were collected from 148 surgical patients, and the demographic and clinical characteristics were collected. Immunohistochemical staining and western blot analysis of P504S/AMACR, p53, Bcl-2 and Ki-67/MIB-1 were conducted. Statistical analyses were used to compare protein expression in the colorectal tumors and matched normal tissue margins and to identify any associations between them and various clinicopathological parameters. Survival analyses were performed using the Kaplan-Meier method. In the present study, immunohistochemistry and western blot analysis revealed significantly higher expression of all four proteins in colorectal tumors compared with matched normal tissue margins (P<0.001). Spearman's rank correlation analysis revealed that Bcl-2 expression was negatively correlated with pathological grade and Tumor-Node-Metastasis (TNM) stage (−0.827 and −0.388, respectively; P<0.05). Bcl-2 expression was revealed to be a significant prognostic indicator of colorectal carcinoma [relative risk (95% CI), 0.703 (0.552–0.895); P<0.05]. The log-rank test revealed a significant association between low Bcl-2 expression and reduced overall survival (P=0.039), as well as a significant association between older age (>55 years) and reduced overall survival (P<0.001) in Chinese patients with colorectal carcinoma. In conclusion, low expression of Bcl-2 is significantly correlated with advanced pathological grade and TNM stage and is a prognostic indicator of reduced overall survival in young Chinese patients with colorectal carcinoma.

Analysis of Volatile Organic Compounds Released from SW480 Colorectal Cancer Cells and from the Blood of the Tumor-Bearing Mice

Background: Volatile organic compound (VOC) analysis provides an elegant approach for colorectal cancer screening. Many studies have focused on the relationship between VOCs in exhaled breath and cancer. However, many factors can affect the presence of VOCs in exhaled breath, such as smoking and diet. An organic compound with a higher vapor pressure or volatility can be detected in the headspace of cancer cells or blood samples. Therefore, analyzing VOCs in the blood of rats inoculated with colorectal cancer tissue and in SW480 medium from cultured colorectal cancer cells provides more accurate results. Methods: After collecting venous blood from rats inoculated with cancer cells at different times, removing cancer tissue from the inoculated rats, and harvesting the medium of cancer cells cultured in the presence or absence of chemotherapy drug and of intestinal epithelial cells, we used solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) to analyze the headspace of the blood and media to evaluate the VOC profiles. Statistical analysis was conducted using principal component analysis (PCA) and orthogonal partial least squares(OP-LSDA). Findings: In the in vivo and in vitro analyses of the colorectal cancer samples, we found a variety of compounds, such as cyclohexanone; 1-hexanol, 2-ethyl-; butylated hydroxytoluene; cyclotrisiloxane, hexamethyl-; pentanoic acid, 2,2,4-trimethyl-3-hydroxy-isobutyl ester; and acetone. Among these compounds, butylated hydroxytoluene is unique with regard to its presence during the processes of tumor growth and resection; it is also present during the processes of tumor cell growth and necrosis. Acetone showed unique trends in the in vivo experimental group. Interpretation: By analyzing VOC fingerprints relating to CRC, we found that butylated hydroxytoluene and acetone have unique signatures that may provide the basis for clinical diagnosis and disease assessment. Funding Statement: The project is funded by the National Natural Science Foundation of China (No. 81402462); Nn10 program and Distinguished Young Scholars Fund of Harbin Medical University Cancer Hospital; The Yuweihan Fund for Distinguished Young Scholars of Harbin Medical University; Harbin Science and Technology Innovation Scholars Fund (2017RAXXJ087); Heilongjiang Province Postdoctoral Research Fund. Declaration of Interest: The authors declare no potential conflicts of interest. Ethics Approval Statement: This study’s protocol was approved by the Ethics Committee at the First Affiliated Hospital of Harbin Medical University (No.2017005).

Detection of gas components as a novel diagnostic method for colorectal cancer.

BackgroundThe fecal occult blood test (FOBT) is widely accepted as the most economic and non‐invasive screening method for colorectal cancer (CRC). However, the FOBT is inconvenient because it requires a fecal sample and shows limited accuracy. Alternatively, we hypothesized that fecal gas compounds from bowel movements may be a non‐invasive biomarker for CRC.MethodsGas compounds were collected from the bowel movements of 30 patients with CRC and from 26 healthy controls. The patient group comprised 17 males and 13 females, and the average age was 68 years. Additionally, 22 patients had colon cancer, and eight patients had rectal cancer. Gas compounds were analyzed using gas chromatography and compared with those from healthy controls.ResultsIn the gas analysis, methyl mercaptan was significantly higher in the CRC group than in the control group. Hydrogen was significantly lower in the CRC group than in the control group and was correlated with tumor depth and advanced disease stage. Sensitivity, specificity, and accuracy of detection by a discriminant formula were 90%, 57.7%, and 75%, respectively.ConclusionGas compounds from defecation constitute a promising, novel non‐invasive approach for CRC screening. (UMIN000028256)

Abstract IA13: Stool DNA detection of colorectal neoplasia

Abstract IA13: Stool DNA detection of colorectal neoplasia

Racial/Ethnic Disparities in Colorectal Cancer Screening Across Healthcare Systems.

Racial/ethnic disparities in colorectal cancer (CRC) screening and diagnostic testing present challenges to CRC prevention programs. Thus, it is important to understand how differences in CRC screening approaches between healthcare systems are associated with racial/ethnic disparities. This was a retrospective cohort study of patients aged 50-75 years who were members of the Population-based Research Optimizing Screening Through Personalized Regimens cohort from 2010 to 2012. Data on race/ethnicity, CRC screening, and diagnostic testing came from medical records. Data collection occurred in 2014 and analysis in 2015. Logistic regression models were used to calculate AORs and 95% CIs comparing completion of CRC screening between racial/ethnic groups. Analyses were stratified by healthcare system to assess differences between systems. There were 1,746,714 participants across four healthcare systems. Compared with non-Hispanic whites (whites), odds of completing CRC screening were lower for non-Hispanic blacks (blacks) in healthcare systems with high screening rates (AOR=0.86, 95% CI=0.84, 0.88) but similar between blacks and whites in systems with lower screening rates (AOR=1.01, 95% CI=0.93, 1.09). Compared with whites, American Indian/Alaskan Natives had lower odds of completing CRC screening across all healthcare systems (AOR=0.76, 95% CI=0.72, 0.81). Hispanics had similar odds of CRC screening (AOR=0.99, 95% CI=0.98, 1.00) and Asian/Pacific Islanders had higher odds of CRC screening (AOR=1.16, 95% CI=1.15, 1.18) versus whites. Racial/ethnic differences in CRC screening vary across healthcare systems, particularly for blacks, and may be more pronounced in systems with intensive CRC screening approaches.