Screening Tool For Colorectal Cancer Research Articles

Abstract LB109: Detection of high grade intraepithelial neoplasia in colorectal cancer using a new blood-based multiplex septin9 methylation assay

Abstract Colorectal cancer (CRC) is the third most common cancer worldwide, and regular screening is effective in reducing its mortality. Epi proColon was the first blood-based Septin9 gene methylation assay approved by the US FDA for CRC screening. However, the broader application of this assay has been hindered by its relatively lower sensitivity in detecting early-stage CRC and precancerous lesions. In this study, we developed a new multiplex Septin9 methylation assay, named ColonUSK, which simultaneously detects two CpG-rich subregions in the promoter of the Septin9 gene and an internal control in a single reaction. In comparison with the Sepin9 assay targeting only one CpG-rich subregion, this new assay demonstrated improved sensitivity, with a detection limit as low as 12pg of the positive DNA. To assess its value in CRC screening, we conducted an opportunistic screening study involving a total of 1366 subjects. Blind testing was performed to evaluate ColonUSK in comparison with clinical diagnosis using colonoscopy and pathological examination (the clinical gold standard). The clinical sensitivities of ColonUSK for detecting CRC and advanced adenoma were 77.34% (95% CI: 72.89%-81.26%) and 25.26% (95% CI: 17.16%-35.41%), respectively. The clinical specificity of the assay for non-CRC cases was 95.95% (95% CI: 94.36%-97.13%). Notably, ColonUSK was able to detect 54.29% of cases with high-grade intraepithelial neoplasia. The Kappa test value for this experiment was 0.76, indicating a high degree of consistency between ColonUSK and pathological diagnosis. Our results suggest that ColonUSK holds potential as a non-invasive screening tool for colorectal cancer. Citation Format: Youming Wu, Yongqin Tong Tong, Haitao Zhang, Yun Li, Ming Li, Lili Qiu, Wenlan Liu, Siqing Mei, Yu Mao, Yanhua Cao, Caiyan Su, Wentao Yu, Junli Wang, Taizhong Wang, Zhongyuan Zhu, Dehua Derek Yu. Detection of high grade intraepithelial neoplasia in colorectal cancer using a new blood-based multiplex septin9 methylation assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB109.

The potential of machine learning models to identify malnutrition diagnosed by GLIM combined with NRS-2002 in colorectal cancer patients without weight loss information

Background & AimsThe key step of the Global Leadership Initiative on Malnutrition (GLIM) is nutritional risk screening, while the most appropriate screening tool for colorectal cancer (CRC) patients is yet unknown. The GLIM diagnosis relies on weight loss information, and bias or even failure to recall patients’ historical weight can cause misestimates of malnutrition. We aimed to compare the suitability of several screening tools in GLIM diagnosis, and establish machine learning (ML) models to predict malnutrition in CRC patients without weight loss information. MethodsThis multicenter cohort study enrolled 4487 CRC patients. The capability of GLIM diagnoses combined with four screening tools in predicting survival probability was compared by Kaplan-Meier curves, and the most accurate one was selected as the malnutrition reference standard. Participants were randomly assigned to a training cohort (n=3365) and a validation cohort (n=1122). Several ML approaches were adopted to establish models for predicting malnutrition without weight loss data. We estimated feature importance and reserved the top 30% of variables for retraining simplified models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to assess and compare model performance. ResultsNRS-2002 was the most suitable screening tool for GLIM diagnosis in CRC patients, with the highest hazard ratio (1.59; 95% CI, 1.43-1.77). A total of 2076 (46.3%) patients were malnourished diagnosed by GLIM combined with NRS-2002. The simplified random forest (RF) model outperformed other models with an AUC of 0.830 (95% CI, 0.805-0.854), and accuracy, sensitivity and specificity were 0.775, 0.835 and 0.742, respectively. We deployed an online application based on the simplified RF model to accurately estimate malnutrition probability in CRC patients without weight loss information (https://zzuwtt1998.shinyapps.io/dynnomapp/). ConclusionsNutrition Risk Screening 2002 was the optimal initial nutritional risk screening tool in the GLIM process. The RF model outperformed other models, and an online prediction tool was developed to properly identify patients at high risk of malnutrition.

MiRNA as a Biomarker for the Early Detection of Colorectal Cancer.

MicroRNAs (miRNAs) are short, non-coding RNA segments that can be detected in a variety of clinical samples, including serum, stool, and urine. While miRNAs were initially known for their effect on post-translational gene expression, the last decade of research has shown them to be promising biomarkers for the detection of many types of cancer. This paper explores the use of miRNA detection as a tool for colorectal cancer (CRC) screening. We discuss the current state of miRNA detection, compare it to the existing CRC screening tools, and highlight the advantages and drawbacks of this approach from a clinical and logistical perspective. Our research finds that miRNA-based tests for CRC show great potential, but that widespread clinical adoption will be conditional on future research overcoming key hurdles.

Management of colorectal cancer screening backlog due to the COVID-19 pandemic: A retrospective analysis of the use of a colorectal cancer screening clinical-decision support tool in Argentina

BackgroundThe COVID-19 pandemic created a backlog in colorectal cancer (CRC) screening and surveillance colonoscopies. The real impact in Argentina is not fully known. GoalTo estimate the impact of the COVID-19 pandemic on CRC prevention by comparing the number of CRC screening and surveillance consults in a clinical decision support-tool used in Argentina before, during and after pandemic lockdown. MethodsWe analyzed data from May 2019 to December 2021 from CaPtyVa, a clinical decision support tool for CRC screening and surveillance. Queries were divided in pre-pandemic (May 2019 to March 2020), lockdown (April 2020 to December 2020), and post-lockdown (January 2021 to December 2021). The number of CRC monthly screening and surveillance visits were compared among the three periods and stratified according to CRC risk. ResultsOverall, 27,563 consults were analyzed of which 9035 were screening and 18,528 were surveillance. Pre-pandemic, the median number of screening consults was 346 per month (IQR25–75 280–410). There was a decrease to 156 (80–210)/month (p<0.005) during lockdown that partially recovered during post-lockdown to 230 (170–290)/month (p=0.05). Pre-pandemic, the median number of surveillance consults was 716 (560–880)/month. They decreased to 354 (190–470)/month during lockdown (p<.05) and unlike screening, completely recovered during post-lockdown to 581 (450–790)/month. ConclusionsThere was a >50% decrease in the number of CRC screening and surveillance consults registered in CaPtyVa during lockdown in Argentina. Post-lockdown, surveillance consults recovered to pre-pandemic levels, but screening consults remained at 66% of pre-pandemic levels. This has implications for delays in CRC diagnoses and patient outcomes.

2002 An observational study of the effectiveness of FIT test as a risk stratification tool in frail patients presenting with anaemia

Abstract Introduction Faecal-immunochemical-test is employed as a screening tool for colorectal cancer. Our observational study examined the FIT in primary care as a risk stratification tool in frail patients. Method The records of 217 frail patients over a 24-month period were analysed. Patients with haematological indices of anaemia were offered FIT to detect GI haemorrhage as part of assessment for selection for lower GI investigations. Patients were risk stratified based on FIT results based on the presence or absence of red flags. Patients who were FIT positive were referred for urgent lower GI endoscopy versus those who were FIT negative were managed without bowel investigations unless there were red flags such as abdominal mass, changed bowel habits or family history of bowel cancer. Results Of 217 patients over a 24-month period of these 42 patients (19.4%) were FIT positive. All of these (n = 42) underwent colonoscopy of which 15 (normal)16 (colonic polyps) 6 (diverticulosis) 3 (colorectal cancer). Of the 42 FIT positive patients 16 were on direct oral anticoagulant (DOAC). Patients on DOACs and those on dual anti platelet agents were more likely to be FIT positive. We also found a positive correlation between higher frailty indices, HAS BLED scores and chronic kidney disease and low creatinine clearance r=0.82, p=0.001. Despite the small numbers in this study the correlation is statistically significant Conclusion There is a statistically significant positive correlation of FIT positive and frailty indices with DOACs, Dual anti platelet agents, CKD, low creatinine clearance (r=0.82 and p=0.001). Following this the HASBLED scores increased hence our practices implemented an enhanced surveillance of monitoring these patients quarterly due to the increased risk. We advocate frailty indices should be incorporated in the HAS BLED scores for improved patient safety.

Association of Methylenetetrahydrofolate Reductase rs1801133 Gene Polymorphism with Cancer Risk and Septin 9 Methylation in Patients with Colorectal Cancer.

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 recalibration and redevelopment of a model to calculate patients' probability of completing a colonoscopy following an abnormal fecal test.

Fecal immunochemical testing (FIT) is an effective screening tool for colorectal cancer. If an FIT is abnormal, a follow-up colonoscopy is necessary to remove polyps or find cancers. We sought to develop a usable risk prediction model to identify patients unlikely to complete a colonoscopy following an abnormal FIT test. We recalibrated and then redeveloped a prediction model in federally qualified health centers (FQHCs), using a retrospective cohort of patients aged 50-75 with an abnormal FIT test and clinical data. Logistic and Cox regressions were used to recalibrate and then redevelop the model. The initial risk model used data from eight FQHCs (26 clinics) including 1723 patients. When we applied the model to a single large FQHC (34 clinics, 884 eligible patients), the model did not recalibrate successfully (c-statistic dropped more than 0.05, from 0.66 to 0.61). The model was redeveloped in the same FQHC in a cohort of 1401 patients with a c-statistic of 0.65. The original model developed in a group of FQHCs did not adequately recalibrate in the single large FQHC. Health system, patient characteristics or data differences may have led to the inability to recalibrate the model. However, the redeveloped model provides an adequate model for the single FQHC.

Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy

Patients affected by inflammatory bowel disease (IBD) have a two-fold higher risk of developing colorectal cancer (CRC) than the general population. IBD-related CRC follows a different genetic and molecular pathogenic pathway than sporadic CRC and can be considered a complication of chronic intestinal inflammation. Since inflammation is recognised as an independent risk factor for neoplastic progression, clinicians strive to modulate and control disease, often using potent therapy agents to achieve mucosal healing and decrease the risk of colorectal cancer in IBD patients. Improved therapeutic control of inflammation, combined with endoscopic advances and early detection of pre-cancerous lesions through surveillance programs, explains the lower incidence rate of IBD-related CRC. In addition, current research is increasingly focused on translating emerging and advanced knowledge in microbiome and metagenomics into personalised, early, and non-invasive CRC screening tools that guide organ-sparing therapy in IBD patients. This review aims to summarise the existing literature on IBD-associated CRC, focusing on new insights into the alteration of the intestinal barrier and the interactions with the gut microbiome as the initial promoter. In addition, the role of OMIC techniques for precision medicine and the impact of the available IBD therapeutic armamentarium on the evolution to CRC will be discussed.

Management of colorectal cancer screening backlog due to the COVID-19 pandemic: A retrospective analysis of the use of a colorectal cancer screening clinical-decision support tool in Argentina

BackgroundThe COVID-19 pandemic created a backlog in colorectal cancer (CRC) screening and surveillance colonoscopies. The real impact in Argentina is not fully known. GoalTo estimate the impact of the COVID-19 pandemic on CRC prevention by comparing the number of CRC screening and surveillance consults in a clinical decision support-tool used in Argentina before, during and after pandemic lockdown. MethodsWe analyzed data from May 2019 to December 2021 from CaPtyVa, a clinical decision support tool for CRC screening and surveillance. Queries were divided in pre-pandemic (May 2019 to March 2020), lockdown (April 2020 to December 2020), and post-lockdown (January 2021 to December 2021). The number of CRC monthly screening and surveillance visits were compared among the three periods and stratified according to CRC risk. ResultsOverall, 27,563 consults were analyzed of which 9035 were screening and 18,528 were surveillance. Pre-pandemic, the median number of screening consults was 346 per month (IQR25–75 280–410). There was a decrease to 156 (80–210)/month (p<0.005) during lockdown that partially recovered during post-lockdown to 230 (170–290)/month (p=0.05). Pre-pandemic, the median number of surveillance consults was 716 (560–880)/month. They decreased to 354 (190–470)/month during lockdown (p<.05) and unlike screening, completely recovered during post-lockdown to 581 (450–790)/month. ConclusionsThere was a >50% decrease in the number of CRC screening and surveillance consults registered in CaPtyVa during lockdown in Argentina. Post-lockdown, surveillance consults recovered to pre-pandemic levels, but screening consults remained at 66% of pre-pandemic levels. This has implications for delays in CRC diagnoses and patient outcomes.

A systematic review of microbiome-derived biomarkers for early colorectal cancer detection

Increasing evidence suggests a role of the gut microbiome in the development of colorectal cancer (CRC) and that it can serve as a biomarker for early diagnosis. This review aims to give an overview of the current status of published studies regarding the microbiome as a screening tool for early CRC detection. A literature search was conducted using PubMed and EMBASE in August 2022. Studies assessing the efficacy of microbiome-derived biomarkers based on noninvasive derived samples were included. Not relevant studies or studies not specifying the stage of CRC or grouping them together in the analysis were excluded. The risk of bias for screening tools was performed using the QUADAS-2 checklist. A total of 28 studies were included, ranging from 2 to 462 for CRC and 18 to 665 advanced adenoma patient inclusions, of which only two investigated the co-metabolome as biomarker. The diagnostic performance of faecal bacteria-derived biomarkers had an AUC ranging from 0.28-0.98 for precursor lesions such as advanced adenomas and 0.54-0.89 for early CRC. Diagnostic performance based on the co-metabolome showed an AUC ranging from 0.69 - 0.84 for precursor lesions and 0.65 - 0.93 for early CRC. All models improved when combined with established clinical early detection markers such as gFOBT. A high level of heterogeneity was seen in the number of inclusions and methodology used in the studies. The faecal and oral gut microbiome has the potential to complement existing CRC screening tools, however current evidence suggests that this is not yet ready for routine clinical use.

Developing and testing an educational app on bowel preparation

Background: Colonoscopy is the top investigation tool for colorectal cancer screening. The role of nurses in educating and advising on bowel preparation is essential to prepare patients for colonoscopy. Evidence supports that an interactive patient education smartphone and tablet application (app) leads to better health outcomes. Aims: To develop and evaluate the use of a bowel preparation app in providing knowledge and teaching bowel preparation to improve colonoscopy preparation. Methods: Analyse data from consumer participation and pre-post test methods. Findings: The effectiveness of the app was assessed in four categories: disease-specific content and patient-centred; flexible learning environments and accessibility; elder-friendliness; and usefulness. Overall, 10 people completed the app's feasibility testing and demonstrated a significant improvement in their bowel preparation knowledge (P=0.004) and behaviours (P=0.005). The mean BBPS scores was 7.8 (SD=0.6) and satisfaction with learning using the app was very high (90%). Conclusion: The collaboration with the multidisciplinary team led to the creation of an innovative app with a high level of satisfaction. Thus, interactive app technology in patient education is a feasible alternative method to deliver health information.

S691 Assessment of Occult Blood Testing in Acute Hospital Settings: A Multicenter GI Fellow Driven Study

Introduction: Fecal occult blood testing (FOBT) is an outpatient screening tool for colorectal cancer. It is widely misused in the hospital setting, without accounting for false positives or negatives resulting in unnecessary endoscopic procedures, increased costs and increased length of stay. The aim of our study is to understand the knowledge and current utilization of FOBT among internal medicine residents from multiple programs across the USA. Methods: This is a multicenter survey conducted by a GI fellow in about 25 Internal Medicine Residency programs in Washington-DC, Pennsylvania, New York, New Jersey, Florida, Indiana, Illinois, Georgia, and California. A 15-questionnaire survey on FOBT was emailed on May 18th, 2022, with follow-up reminders until June 3rd, 2022. We considered the end of the academic year as an ideal time to evaluate the understanding and clinical practice of internal medicine trainees. Results: A total of 227 residents responded to our survey {n=96 (42.2%) PGY-I, n=67 (29.5%) PGY-II & n=64 (28.2%) PGY-III}. Overall, 66.7% i.e., 2/3rd of residents sometimes or always ordered FOBT and 67.4% have ordered this test more often in inpatient than in outpatient settings. Approximately 60% of the residents had knowledge of dietary restrictions but only 32% of the residents were questioning the patients before ordering it. The triggers for ordering FOBT were mostly anemia (92.5%) followed by change in stool colour (61%), weight loss (60%) and bleeding per rectum (47.5%). 62% of respondents felt influenced by their supervisors but 57.2% felt that FOBT results will change their management. Overall, as postgraduate year training increased, trainees were less likely to order FOBT for suspected GI bleeding (Table). Conclusion: Our survey results showed that residents were influenced by their supervisors and ordered FOBT largely in the inpatient setting. Although there was noted improvement in understanding of the futility of FOBT in suspected acute GI bleeding, more than half of final year trainees would still order FOBT first. There is a need for better education of internal medicine trainees in the utilization of FOBT. Table 1. - Statistical analysis comparing the level of training with preference to FOBT vs. GI Consult for a suspected GI Bleed For a suspected GI Bleed, which of the following would you consider first Logistic regression analysis, comparing PGY-I with PGY-II & III Postgraduate Year GI Consult FOBT Odds Ratio Confidence Interval P-Value PGY – I 34 (35.4%) 62 (64.6%) Ref Ref Ref PGY – II 28 (41.8%) 39 (58.2%) 0.76 0.40 - 1.44 0.820 PGY – III 37 (43.6%) 27 (56.4%) 0.40 0.21 - 0.77 0.006

S176 Cold Snare Polypectomy in Pedunculated Colorectal Polyps: A Systematic Review and Meta-Analysis

Introduction: Colonoscopy remains an vital tool for colorectal cancer screening and allows for early detection and removal of adenomatous polyps. While several studies have reported on cold snare polypectomy (CSP) and hot snare polypectomy (HSP) in sessile and flat elevated polyps; limited data exists on outcomes in pedunculated polyps. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of CSP for pedunculated polyps. Methods: Multiple databases were searched till June 2022 to identify studies involving the removal of pedunculated polyps with CSP and HSP. (Table) A random effects model was used to calculate outcomes and 95% confidence intervals (CI). Heterogeneity was assessed using I2 test. Our primary goal was to assess pooled rates of immediate and delayed bleeding with CSP. Secondary outcomes included pooled rates of en-bloc & piecemeal resection as well as prophylactic and post resection clipping. Meta-regression was performed to assess if bleeding was affected by polyp location and use of antithrombotics. Results: Six studies including 1025 patients (1,111 polyps with a mean size 4 – 8.5 mm) were analyzed. 116 and 995 polyps were removed with HSP and CSP, respectively. The overall pooled rate of immediate bleeding following CSP was 49.8% (CI 46.8-52.91; I2 98%), which was significantly higher than HSP, RR 7.89 (CI 4.36-14.29; I20%), p< 0.00001 (Figure 1A). The overall pooled rate of delayed bleeding following CSP was 0% (CI 0.00-0.00; I2 0%), which was significantly lower than HSP, RR 0.05 (CI 0.01-0.43; I20%), p=0.006 (Figure 1B). Pooled rate of en-bloc and piecemeal resection with CSP were 99.7% and 0.3%, respectively. Pooled rate of prophylactic clipping and post procedure clipping (to control immediate bleeding) after CSP was 55.3% and 47.2%, respectively. We found no statistical difference in these outcomes when compared to HSP, RR 0.19 (CI 0.01-6.35; I2 85%), p=0.35 and RR 1.73 (CI 0.12-25.5; I2 98%), p=0.69. Meta-regression showed that concurrent use of antithrombotic and/or antiplatelet agents did not have any effect on immediate bleeding following CSP. Right colon polyp location (proximal to the hepatic flexure) significantly correlated with frequency of immediate bleeding. Conclusion: Our analysis shows that CSP is safe and effective for resection of pedunculated colorectal polyps, especially those less than 10 mm in size. While CSP may increase the risk of immediate bleeding, HSP has a higher risk of delayed bleeding.Figure 1.: Forest plots demonstrating the relative risk of immediate (1A) and delayed (1B) bleeding following polypectomy Table 1. - Characteristics of included studies Author, year Study Design Study Country Total Polyps Arimoto, 2022 Prospective, single center Japan 114 Fatima, 2022 Prospective, single center United States 239 Kaltenbach, 2019 Retrospective, multicenter United States 94 Arimoto, 2021 Retrospective, single center Japan 188 Kudo 2021 Retrospective, single center Japan 444 Arimoto, 2020 Retrospective, single center Japan 90 Kaltenbach, 2019 Retrospective, multicenter United States 94

Colorectal cancer screening in sub-Saharan Africa

Colorectal cancer screening in sub-Saharan Africa

Microbial multidimensional signature assessment reveals microbial SNVs as the superior non‐invasive biomarkers for early detection of colorectal cancer

BackgroundThe early detection of colorectal cancer (CRC), especially at precancerous adenoma stage, significantly reduces its incidence. Gut microbiome has become a promising non‐invasive tool for CRC screening, whereas the potential of microbial multidimensional signatures remains poorly understood. Here we performed a cross‐cohort analysis to evaluate the capability of microbial multidimensional biomarkers for adenoma detection.DesignWhole metagenome sequencing data of four public datasets including 183 adenoma patients and 439 healthy controls were reprocessed consistently to obtain taxonomic‐, functional‐ and single‐nucleotide variants (SNVs)‐profiling. With MMUPHin, differential multidimensional signatures were identified after adjusting confounders, based on which random forest (RF) models were constructed and then optimized by recursive feature elimination. Finally, internal validation and external validation with in‐house dataset (10 controls and 6 adenomas) and five resampled datasets were conducted to further assess the robustness of the best biomarker panel.ResultsThe integrated analysis identified 103 multi‐kingdom differential species between adenoma and control group, of which 15 optimal species were selected to construct a RF model achieving an AUC of 0.75. Meanwhile, the model constructed with 31 optimal biomarkers out of 386 differential KO genes reached an AUC of 0.74. Notably, the diagnostic model with 75 SNVs from 10 species showed superior accuracy (AUC = 0.85) with high specificity to adenoma. Co‐abundance analysis revealed intensive bacterial‐fungal associations in line with functional abnormalities related to microbial quorum sensing, purine and butanoate metabolism.ConclusionMicrobial SNV biomarkers outperform other biomarkers and display high specificity to adenoma, which may serve as a novel non‐invasive tool for early detection of CRC. Furthermore, multidimensional signatures provide potential therapeutic targets for adenoma.

Identification of microRNA Targets in colorectal cancer through Data Sequencing

Colorectal cancer (CRC) is the third leading cause of cancer‐related mortality globally. MicroRNAs (miRNAs, miRs), a class of small non‐coding RNA molecules, have demonstrated important roles in carcinogenesis and its progression through the regulation of the epithelialmesenchymal transition (EMT), oncogenic signaling pathways, and metastasis. Despite the increase in miRNA studies and extensive analyzes of their expression, the role and function of many individual miRNAs in CRC remains poorly understood. The aim of this study was to identify miRNA targets in CRC through data sequencing, which could be a solid prognostic prediction tool and help clinical strategy.MethodsCRC gene expression data sets were collected from the public database, The Cancer Genome Atlas (TCGA). In addition, web‐based tools were used to explore TCGA data, specifically the one developed by the Broad Institute TCGA GDAC Firehose, which provides data sets, algorithms, and analysis results standardized for TCGA. This pipeline has the following steps: The CLR (Context Likelihood of Relatedness) approach is applied to infer putative miRNA regulatory connections: gene; miRNA filtering: gene pairs based on Pearson's correlation (&lt;= ‐0.3); and miRNA filtering: gene pairs based on predicted interactions in three sequence prediction databases (Miranda, Pictar, Targetscan). The CLR algorithm was applied on 617 miRs and 18012 mRNAs across 220 samples. After 2 filtering steps, the number of 9 miR:genes pairs were detected.ResultsThe initial search with the term “Colorectal adenocarcinoma”, “COADREAD” yielded 631 cases. After the analysis of these samples, data on the significance miR:gene pairs were obtained and Table 1 shows the results of miR:gene pairs with corr &lt; ‐0.30 and predicted interactions in three sequence prediction databases. About the miRNA connections, Table 2 shows all miRNA hubs with their associated genes in the putative direct target network. Finally, about gene connections, Table 3 shows all gene hubs with their associated miRNAs in the putative direct target network.ConclusionThe use of miRNAs as biomarkers for CRC could provide a new and less invasive technique to detect CRC and help determine prognosis. These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately, with the potential to develop new therapeutic targets. Therefore, it is proposed to develop a screening panel that should consist of multiple miRNAs that would provide a more accurate and efficient screening tool for CRC.

A Metabolomics-Based Screening Proposal for Colorectal Cancer.

Colorectal cancer (CRC) is a high incidence disease, characterized by high morbidity and mortality rates. Early diagnosis remains challenging because fecal occult blood screening tests have performed sub-optimally, especially due to hemorrhoidal, inflammatory, and vascular diseases, while colonoscopy is invasive and requires a medical setting to be performed. The objective of the present study was to determine if serum metabolomic profiles could be used to develop a novel screening approach for colorectal cancer. Furthermore, the study evaluated the metabolic alterations associated with the disease. Untargeted serum metabolomic profiles were collected from 100 CRC subjects, 50 healthy controls, and 50 individuals with benign colorectal disease. Different machine learning models, as well as an ensemble model based on a voting scheme, were built to discern CRC patients from CTRLs. The ensemble model correctly classified all CRC and CTRL subjects (accuracy = 100%) using a random subset of the cohort as a test set. Relevant metabolites were examined in a metabolite-set enrichment analysis, revealing differences in patients and controls primarily associated with cell glucose metabolism. These results support a potential use of the metabolomic signature as a non-invasive screening tool for CRC. Moreover, metabolic pathway analysis can provide valuable information to enhance understanding of the pathophysiological mechanisms underlying cancer. Further studies with larger cohorts, including blind trials, could potentially validate the reported results.

Colorectal Cancer Screening in Inflammatory Bowel Diseases—Can Characterization of GI Microbiome Signatures Enhance Neoplasia Detection?

Current noninvasive methods for colorectal cancer (CRC) screening are not optimized for persons with inflammatory bowel diseases (IBDs), requiring patients to undergo frequent interval screening via colonoscopy. Although colonoscopy-based screening reduces CRC incidence in IBD patients, rates of interval CRC remain relatively high, highlighting the need for more targeted approaches. In recent years, the discovery of disease-specific microbiome signatures for both IBD and CRC has begun to emerge, suggesting that stool-based biomarker detection using metagenomics and other culture-independent technologies may be useful for personalized, early, noninvasive CRC screening in IBD patients. Here we discuss the utility of the stool microbiome as a noninvasive CRC screening tool. Comparing the performance of multiple microbiome-based CRC classifiers, including several multi-cohort meta-analyses, we find that noninvasive detection of colorectal adenomas and carcinomas from microbial biomarkers is an active area of study with promising early results.

Abstract PO-253: Overcoming barriers to colorectal cancer screening for underserved patients: Lessons from the COVID-19 pandemic

Abstract Introduction This patient navigation initiative works to address cancer health disparities by improving education and access to screening and cancer care. This initiative includes partnerships with local Federally Qualified Health Centers (FQHCs) and primary care physicians (PCPs), primarily focused on increasing colorectal cancer (CRC) screening rates among underserved populations in Western New York (WNY) who may have low health literacy. Grounded in health services research, we aimed to improve clinical care by implementing evidence-based guidelines into practice by working directly with underserved communities in our area to improve CRC screening rates at an urban FQHC. Methods Throughout the COVID-19 pandemic, our navigators pivoted to a hybrid schedule with remote access to health systems, splitting time between our cancer center and remotely at home until allowed back on-site to work at the FQHC. Colonoscopy halted in NY between March and June 2020, resulting in scheduling challenges due to significant backlogs of cancelled procedures during the shutdown and regional hold on elective procedures. Endoscopists across WNY had reduced capacity for postponed procedures, leading to the prioritization of scheduling for symptomatic patients. Therefore, navigators focused screening efforts on widely disseminating stool-based tests to patients due for average-risk CRC screening and prioritizing patients with positive screening results to coordinate colonoscopy appointments. Results Between April 2020 through March 2021, our pre-pandemic goal was to educate 550 patients and screen 300 patients. During this timeframe, navigators provided screening education to 632 patients and screened 232 patients despite significant challenges presented by the COVID-19 pandemic. With many colonoscopy procedures being cancelled and/or rescheduled, stool-based tests were widely available and became a more common choice for patients. To date, since April 2020, navigators have educated 807 patients and have navigated 306 patients to complete CRC screening. Of those 306 patients, 234 chose to complete at-home stool-based testing. In 2020, CRC screening rates remained over 50%, exceeding national FQHC targets. This was achieved through targeted patient outreach, education, and navigation, despite significant challenges with the shutdown and the COVID-19 pandemic. Conclusions Stool-based tests paired with targeted outreach and education were an efficient tool for CRC screening during this challenging time. Navigators regularly cross-check records to be sure results are received by ordering physicians and properly coded for accurate data reporting. This is especially important for positive test results and timely follow up, which may lead to improved health outcomes. Moving forward, this paired approach may be an effective strategy for improving screening rates among hard-to-reach patient populations and patients facing substantial barriers to accessing routine medical care. Citation Format: Kathryn M. Glaser, Christina Crabtree-Ide, Alyssa McNulty, Ellis Gomez, Nicole Donofrio, Tessa Flores, Mary E. Reid. Overcoming barriers to colorectal cancer screening for underserved patients: Lessons from the COVID-19 pandemic [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-253.

Risk of Diabetes in Subjects with Positive Fecal Immunochemical Test: A Nationwide Population-Based Study.

Background Positive fecal immunochemical test (FIT) results have been recently suggested as a risk factor for systemic inflammation. Diabetes induces inflammation in the gastrointestinal tract via several ways. We investigated the association between FIT results and the incidence of diabetes.Methods A total of 7,946,393 individuals aged ≥50 years from the National Cancer Screening Program database who underwent FIT for colorectal cancer (CRC) screening from 2009 to 2012 were enrolled. The primary outcome was newly diagnosed diabetes based on the International Classification of Disease 10th revision codes and administration of anti-diabetic medication during the follow-up period.Results During a mean follow-up of 6.5 years, the incidence rates of diabetes were 11.97, 13.60, 14.53, and 16.82 per 1,000 personyears in the FIT negative, one-positive, two-positive, and three-positive groups, respectively. The hazard ratios (HRs) for the incidence of diabetes were 1.14 (95% confidence interval [CI], 1.12 to 1.16; HR, 1.21; 95% CI, 1.16 to 1.27; and HR, 1.40; 95% CI, 1.28 to 1.55) in the one-positive, two-positive, and three-positive FIT groups compared with the FIT negative group, respectively. The effect was consistent in individuals with normal fasting blood glucose (adjusted HR 1.55 vs. 1.14, P for interaction <0.001).Conclusion Positive FIT results were associated with a significantly higher risk of diabetes, suggesting that the FIT can play a role not only as a CRC screening tool, but also as a surrogate marker of systemic inflammation; thus, increasing the diabetes risk.