Early Colorectal Cancer Screening Research Articles

The tissue and circulating cell‐free DNA‐derived genetic landscape of premalignant colorectal lesions and its application for early diagnosis of colorectal cancer

AbstractColorectal adenomas (CRAs) represent precancerous lesions that precede the development of colorectal cancer (CRC). Regular monitoring of CRAs can hinder the progression into carcinoma. To explore the utility of tissue DNA and circulating cell‐free DNA (cfDNA) in early diagnosis of CRC, we retrospectively sequenced paired tissue and plasma samples from 85 patients with conventional CRAs. The genetic alterations identified were compared with those from 78 stage‐I CRC patients (CRC‐I) in the ChangKang project. Within the CRA cohort, we pinpointed 12 genes, notably APC, KRAS, and SOX9, that exhibited significant mutated rates in tissue. Patients harboring KMT2C and KMT2D mutations displayed persistent polyps. By comparing with the mutational profiles of metastatic CRC plasma samples, we found that ZNF717 was exclusively mutated in CRAs, while KMT2C and KMT2D mutations were detected in both CRA and CRC. The presence of cfDNA mutations in plasma was validated through polymerase chain reaction, enhancing the feasibility of using cfDNA mutations for early CRC screening. Compared with CRC‐I, CRAs exhibited a reduced frequency of TP53 and PIK3CA somatic mutations and underwent non‐neutral evolution more often. We established a random forest model based on 15 characteristic genes to distinguish CRA and CRC, achieving an area under the curve of 0.89. Through this endeavor, we identified two novel genes, CNTNAP5 and GATA6, implicated in CRC carcinogenesis. Overall, our findings reveal convincing biomarkers markers for detecting CRAs with a propensity for CRC development, highlighting the importance of early genetic screening in CRC prevention.

A lighter hybrid feature fusion framework for polyp segmentation

Colonoscopy is widely recognized as the most effective method for the detection of colon polyps, which is crucial for early screening of colorectal cancer. Polyp identification and segmentation in colonoscopy images require specialized medical knowledge and are often labor-intensive and expensive. Deep learning provides an intelligent and efficient approach for polyp segmentation. However, the variability in polyp size and the heterogeneity of polyp boundaries and interiors pose challenges for accurate segmentation. Currently, Transformer-based methods have become a mainstream trend for polyp segmentation. However, these methods tend to overlook local details due to the inherent characteristics of Transformer, leading to inferior results. Moreover, the computational burden brought by self-attention mechanisms hinders the practical application of these models. To address these issues, we propose a novel CNN-Transformer hybrid model for polyp segmentation (CTHP). CTHP combines the strengths of CNN, which excels at modeling local information, and Transformer, which excels at modeling global semantics, to enhance segmentation accuracy. We transform the self-attention computation over the entire feature map into the width and height directions, significantly improving computational efficiency. Additionally, we design a new information propagation module and introduce additional positional bias coefficients during the attention computation process, which reduces the dispersal of information introduced by deep and mixed feature fusion in the Transformer. Extensive experimental results demonstrate that our proposed model achieves state-of-the-art performance on multiple benchmark datasets for polyp segmentation. Furthermore, cross-domain generalization experiments show that our model exhibits excellent generalization performance.

Diagnostic and screening potential of plasma exosome miR‑99b‑5p and its combination with other miRNAs for colorectal cancer.

Extracellular vesicles (EVs) secreted by tumor cells have been documented to hold viable biomarker potential. Therefore, the present study evaluated the potential clinical value of EV-microRNAs (miRNAs or miRs) in the plasma exosomes of patients with colorectal cancer (CRC) for the early diagnosis and screening of CRC. In total, 95 plasma samples were collected at The Third Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) between 2017 and 2019. Specifically, 68 samples were from patients with CRC and 27 were from healthy control (HC) donors. High-throughput sequencing was used to detect the expression of miRNAs in the isolated plasma EVs, which was subsequently verified by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic potential of single and combined miRNAs for CRC. Bioinformatics analysis was employed to predict the target genes of candidate miRNAs. Compared with those in the HC group, the CRC group expressed higher levels of miR-99b-5p and miR-409-3p, especially during the early stages of CRC. Clinicopathological analysis confirmed the higher expression levels of miR-99b-5p during the early stages, as well as higher expression levels in the colon compared with those in the rectum. ROC curve analysis revealed that the area under the curve (AUC) of miR-99b-5p for the diagnosis of early CRC was 73.5% (P=0.007). The early diagnostic capability of miR-99b-5p combined with miR-409-3p for CRC was evaluated, and the AUC was found to be 74.1% (P=0.006). In addition, the AUC of the combination of miR-99b-5p, miR-409-3p and carcinoembryonic antigen was 81.2% (P<0.001), indicating that this three-parameter combination displayed higher diagnostic power compared with any single miRNA for early CRC screening. The results from the present study suggest that the expression of miR-99b-5p in plasma exosomes is significantly upregulated in CRC, which holds potential for the early diagnosis of this cancer type. Such potential can be enhanced further by combining it with other miRNAs. Therefore, the present study provides a comprehensive but preliminary insight for the viability of miR-99b-5p (alone or combined with other miRNAs) for CRC diagnosis, which requires further exploration in the future.

Risk of Colorectal Cancer among Patients with One or Multiple Metabolic Syndrome Components

Background/Objectives: Dysfunctions of metabolic syndrome (MetS) have been identified as a significant risk factor for colorectal cancer (CRC). However, current colon cancer guidelines do not classify patients with MetS as high risk, thereby leaving these individuals vulnerable. Consequently, we explored the relationship between MetS, its individual components, and the development of CRC in a cohort of patients with MetS to assess the necessity for CRC screening in these individuals. Methods: This study included patients ages 18 and older that received a service from the Marshall-Health (MH) practice plan, Cabell-Huntington Hospital (CHH), MU/JCESOM’s Edwards Comprehensive Cancer Center (ECCC), or the University of Kentucky HealthCare (UKHC) system between 2010 and 2018. We implemented log-binomial regression models to assess the individual and collective effects of MetS components after adjusting other CRC risk factors. Results: Given that CRC prevalence increases in the older population (aged 65 years and above), and that multiple components of MetS are observed within the same population, we analyzed the concurrent impact of all MetS components on CRC. Log-binomial regression models were implemented to assess the risk of CRC due to MetS components after adjusting other risk factors. Conclusions: We identified specific components that markedly increased CRC risk, suggesting that individuals with these components should be prioritized for early screening. These findings could significantly influence early CRC screening protocols, with the ultimate aim to reduce mortality associated with the disease.

Evaluation of Multigene Methylation for Blood-Based Detection of Colorectal Cancer.

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

Liver Disease as a Potential Risk Factor for Colorectal Cancer: A Community Hospital Experience.

Liver disease (LD) is a common pathology worldwide. Many patients remain asymptomatic and undiagnosed. Colorectal cancer (CRC) is a prevalent neoplasm and a leading cause of cancer-related deaths globally. Multiple studies suggest that inflammation in the liver could drive the initiation of colorectal cancer. This five-year (2018-2022) case-control study included 274 patients diagnosed with CRC and adenomas at a community hospital in Houston, Texas. Each patient's medical record was reviewed for pre-existing LD, including steatosis, cirrhosis, primary biliary cirrhosis, and Hepatitis B and C infections. This study aims to investigate the association between LD and CRC risk and assess differences by gender, race, and ethnicity. The study cohort comprised 124 (45.3%) women and 150 (54.7%) men. Data were compared and analyzed using a Chi-squared test for independence and binomial logistic regression. A p-value of < 0.05 was considered statistically significant. Results: Patients with LD had a two-fold increase in the odds of developing CRC compared to those without LD, in both univariate and multivariate analyses (OR 2.13 {95% CI 1.30-3.49}, p = 0.003 / OR 2.30 {95% CI 1.37-3.87}, p = 0.002, respectively). The chi-square test revealed that the association between CRC and LD was stronger in women than in men (p = 0.018 and p = 0.056, respectively). Our study establishes a positive correlation between LD and CRC development, suggesting LD is a potential risk factor for CRC, particularly in women. Future research directions include exploring the underlying mechanisms of this association, evaluating the utility of early CRC screening in individuals with LD, and assessing the impact of interventions targeting LD on CRC incidence and mortality.

Early screening of colorectal cancer using feature engineering with artificial intelligence-enhanced analysis of nanoscale chromatin modifications

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity of cancer cells. We deployed an optical spectroscopic nanosensing technique, chromatin-sensitive partial wave spectroscopic microscopy (csPWS), to evaluate the packing density scaling D of the chromatin chain conformation within packing domains from rectal mucosa in 256 patients with varying degrees of progression to colorectal cancer. We found average packing scaling D of chromatin domains was elevated in tumor cells, histologically normal-appearing cells 4 cm proximal to the tumor, and histologically normal-appearing rectal mucosa compared to cells from control patients (p < 0.001). Nuclear D had a robust correlation with the model of 5-year risk of CRC with r2 = 0.94. Furthermore, rectal D was evaluated as a screening biomarker for patients with advanced adenomas presenting an AUC of 0.85 and 85% sensitivity and specificity. artificial intelligence-enhanced csPWS improved diagnostic performance with AUC = 0.90. Considering the low sensitivity of existing CRC tests, including liquid biopsies, to early-stage cancers our work highlights the potential of chromatin biomarkers of field carcinogenesis in detecting early, significant precancerous colon lesions.

Abstract 2439: Potential target genes for early stage detection in Hispanic colorectal cancer

Abstract Background: Colorectal Cancer (CRC) has become the second leading cause of death related to cancer worldwide and the third most common malignancy. CRC tumors are classified into stages to describe the cancer; early (stages I and II) and advanced (stages III and IV). Despite the available screening methods and the scientific efforts in the development of a universal biomarker panel for CRC early detection, there still exists a gap in a reliable non-invasive screening method for the Hispanic community. We aimed to elucidate the most important pathways along with the differential gene expression in early and advanced CRC stages in a Hispanic population. Methods: We examined restrospectively 7 tissue samples from a Puerto Rican Hispanic population recruited throughout the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR) IRB #A2210207. We evaluated transcriptomic changes in advance tumors (n=4) vs. early tumors (n=3) with their respective normal mucosal tissue as negative control. Extracted RNA was sequenced using the Illumina NextSeq (2 × 75bp). The higher-quality reads were aligned, annotated, and quantified to the human genome (hg38) using STAR and RSEM softwares. Gene expression analysis was performed in R statistical software (packages tximport and DESeq2). We compared significantly expressed genes (adjusted p-value &amp;lt;0.05) between study groups (Tumor Advance [TA] vs. Mucosal Advance [MA] and Tumor Early [TE] vs. Mucosal Early [ME]) using Venny, and we performed enrichment analyses and protein-protein interaction networks using Metascape and STRING database, respectively. Results: There were 2284 differentially expressed genes (TA vs. MA) and 984 (TE vs. ME), in which 1736 were unique to advance stages, 436 were unique to early stages and 548 were shared in both tumor stages. Significantly impacted biological processes and pathways include: granulocyte chemotaxis, regulation of inflammatory response, positive regulation of apoptotic process, tissue morphogenesis, G alpha signaling events, interleukin-10 signaling, signaling by interleukins. Additionally, physical and functional interaction networks showed 11 major clusters (≥ 5 genes), which contained several gene hubs including LYN (proto-oncogene), IL-1β, IL-1α, TNF, CCL3, CCL4, CXCR1 and CXCR2 (cytokines/chemokines) among others genes previously reported as CRC biomarkers (DKK1, AQP8, AQP9, CTNNB1, and GNAQ). Discussion/Conclusions: Differential analysis of early CRC tumor samples shows a deregulation of genes related to the inflammatory response which plays an important role in CRC. Modulation of these genes suggests significant potential targets for early detection of CRC in a Hispanic population. Future studies will be focus on the evaluation of selected target genes as a non-invasive early CRC screening method. Citation Format: Elba V. Caraballo, Camille Zenón-Meléndez, Josué Pérez-Santiago, Marcia Cruz-Correa. Potential target genes for early stage detection in Hispanic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2439.

Differentially expressed miR-4310 functions as a tumor suppressor in colorectal cancer.

Colorectal cancer (CRC) is a digestive tract malignancy microRNAs (miRNAs) have attracted much attention as biomarkers in tumor studies. This work focused on the predictive potential and mechanism of miR-4310 in CRC. The miRNA expression profile sets were obtained from the Gene Expression Omnibus (GEO) database, and the appropriate miRNA was screened by GEO2R. The CRC tissues and control tissues of 88 patients with CRC were collected, and the expression of miR-4310 was detected by quantitative real-time PCR, and the efficacy of miR-4310 in diagnosing CRC was evaluated by the receiver operating characteristic curve (ROC). The effects of miR-4310 on the proliferation, migration, and invasion of CRC cells were explored by Cell Counting Kit-8 (CCK-8) and Transwell experiments. Predicting the potential binding sites of miR-4310 and Runt-related transcription factor 1 (RUNX1) by four predictive websites. The relationship between miR-4310 and RUNX1 was confirmed by a double luciferase reporter gene experiment. The bioinformatics analysis found that miR-4310 was differentially expressed in CRC tissues and this finding was certified by the expression of miR-4310 in CRC tissues of collected patients and cultured CRC cell lines. The expression of miR-4310 had a predictive possibility for CRC patients. MiR-4310/RUNX1 pathway had effects on CRC viability, migration, and invasion. MiR-4310 had the potential to be a biomarker for early screening of CRC. MiR-4310 and RUNX1 participated in the regulation of CRC cells.

Routine Fecal Occult Blood Screening and Colorectal Cancer Mortality in Sweden

Population-based colorectal cancer (CRC) screening programs are implemented worldwide, but there are difficulties evaluating their effectiveness. The magnitude of routine CRC screening effectiveness regarding cancer-specific mortality is unclear. To evaluate cancer-specific mortality associated with early vs late or no invitation for routine CRC screening using fecal occult blood testing. This prospective cohort study was performed in the region of Stockholm-Gotland, Sweden, between January 1, 2008, and December 31, 2021. All individuals of the target population of screening born from 1938 to 1954 were included. Data were analyzed from December 12, 2022, to June 25, 2023. Individuals were invited early (2008-2012), late (2013-2015), or not at all to screening with biennial guaiac-based fecal occult blood test. The early invitation group was considered the exposure group and the late or no invitation group was considered the control group. The main outcome was cancer-specific mortality, defined as CRC registered in the Cancer Register with CRC as underlying cause of death in the Cause of Death Register. Excess mortality was calculated as all-cause deaths among the individuals with CRC subtracted from the expected number of deaths had they not had CRC. Poisson regression analysis based on deaths and person-years was used to estimated mortality rate ratio (RR) with 95% CIs, adjusted for follow-up years and attained age. In total, 379 448 individuals (193 436 [51.0%] female) were invited for CRC screening, including 203 670 individuals in the exposure group and 175 778 in the control group. The mean screening participation rate was 63.3%, and there was a maximum of 14 years follow-up. There were 834 CRC deaths in 2 190 589 person-years in the exposure group, compared with 889 CRC deaths in 2 249 939 person-years in the control group. Individuals who underwent early CRC screening had reduced adjusted risk of CRC mortality (RR, 0.86; 95% CI, 0.78-0.95) and excess mortality (RR, 0.84; 95% CI, 0.75-0.93). This prospective cohort study of routine screening with fecal occult blood testing found a 14% decrease in CRC mortality associated with screening. The true association of screening with reduced mortality is expected to be higher due to some coexistence of testing in the control group and CRC deaths diagnosed more than 2 years after screening.

A proteomic classifier panel for early screening of colorectal cancer: a case control study

BackgroundDiagnosis of colorectal cancer (CRC) during early stages can greatly improve patient outcome. Although technical advances in the field of genomics and proteomics have identified a number of candidate biomarkers for non-invasive screening and diagnosis, developing more sensitive and specific methods with improved cost-effectiveness and patient compliance has tremendous potential to help combat the disease.MethodsWe enrolled three cohorts of 479 subjects, including 226 CRC cases, 197 healthy controls, and 56 advanced precancerous lesions (APC). In the discovery cohort, we used quantitative mass spectrometry to measure the expression profile of plasma proteins and applied machine-learning to select candidate proteins. We then developed a targeted mass spectrometry assay to measure plasma concentrations of seven proteins and a logistic regression classifier to distinguish CRC from healthy subjects. The classifier was further validated using two independent cohorts.ResultsThe seven-protein panel consisted of leucine rich alpha-2-glycoprotein 1 (LRG1), complement C9 (C9), insulin-like growth factor binding protein 2 (IGFBP2), carnosine dipeptidase 1 (CNDP1), inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3), serpin family A member 1 (SERPINA1), and alpha-1-acid glycoprotein 1 (ORM1). The panel classified CRC and healthy subjects with high accuracy, since the area under curve (AUC) of the training and testing cohort reached 0.954 and 0.958. The AUC of the two independent validation cohorts was 0.905 and 0.909. In one validation cohort, the panel had an overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89.9%, 81.8%, 89.2%, and 82.9%, respectively. In another blinded validation cohort, the panel classified CRC from healthy subjects with a sensitivity of 81.5%, specificity of 97.9%, and overall accuracy of 92.0%. Finally, the panel was able to detect APC with a sensitivity of 49%.ConclusionsThis seven-protein classifier is a clear improvement compared to previously published blood-based protein biomarkers for detecting early-stage CRC, and is of translational potential to develop into a clinically useful assay.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer.

Colorectal cancer (CRC) is a serious threat worldwide. Although early screening is suggested to be the most effective method to prevent and control CRC, the current situation of early screening for CRC is still not optimistic. In China, the incidence of CRC in the Yangtze River Delta region is increasing dramatically, but few studies have been conducted. Therefore, it is necessary to develop a simple and efficient early screening model for CRC. To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC. Data of 64448 participants obtained from Ningbo Hospital, China between 2014 and 2017 were retrospectively analyzed. The cohort comprised 64448 individuals, of which, 530 were excluded due to missing or incorrect data. Of 63918, 7607 (11.9%) individuals were considered to be high risk for CRC, and 56311 (88.1%) were not. The participants were randomly allocated to a training set (44743) or validation set (19175). The discriminatory ability, predictive accuracy, and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic (ROC) curves and calibration curves and by decision curve analysis. Finally, the model was validated internally using a bootstrap resampling technique. Seven variables, including demographic, lifestyle, and family history information, were examined. Multifactorial logistic regression analysis revealed that age [odds ratio (OR): 1.03, 95% confidence interval (CI): 1.02-1.03, P < 0.001], body mass index (BMI) (OR: 1.07, 95%CI: 1.06-1.08, P < 0.001), waist circumference (WC) (OR: 1.03, 95%CI: 1.02-1.03 P < 0.001), lifestyle (OR: 0.45, 95%CI: 0.42-0.48, P < 0.001), and family history (OR: 4.28, 95%CI: 4.04-4.54, P < 0.001) were the most significant predictors of high-risk CRC. Healthy lifestyle was a protective factor, whereas family history was the most significant risk factor. The area under the curve was 0.734 (95%CI: 0.723-0.745) for the final validation set ROC curve and 0.735 (95%CI: 0.728-0.742) for the training set ROC curve. The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population. The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age, BMI, WC, lifestyle, and family history exhibited high accuracy.

Research progresses and topical issues in early colorectal cancer screening over the past decade

Research progresses and topical issues in early colorectal cancer screening over the past decade

Evaluation of public awareness, knowledge, and attitudes about colorectal cancer screening among the general population in Al-qunfudah.

Colorectal cancer (CRC) is a malignant tumor of the colon and rectum. It can be cured if detected in the early stage through established screening programs. CRC screening is the best way to improve cancer morbidity and mortality. Various approaches such as stool tests, virtual colonoscopy, and sigmoidoscopy are available for early detection. On average, a person after reaching the age of 45 should begin the screening process for CRC periodically for 5 years. Our study aims to measure the population's awareness and knowledge of the effect of CRC screening on CRC outcomes. A cross-sectional study questionnaire was designed and distributed among Saudi residents of the Al-Qunfudah region. A total of 385 participants replied: 55.8% of the participants were males, 78.8% of the study participants mentioned that they had heard about CRC, and 27.3% reported that CRC is common in Al-Qunfudah. In addition, 62.1% knew that CRC is more common in men but only 32.2% had a good awareness level. Moreover, 16.4% of the participants reported that they had received a colonoscopy/sigmoidoscopy; 69.9% did not think of the colonoscopy/sigmoidoscopy procedure as the main barrier to undergoing early screening for CRC. Good awareness regarding CRC was demonstrated in 34.4% of highly educated participants, which was directly associated with levels of education. In conclusion, much more awareness regarding CRC screening is needed in the Al-Qunfudah region. Educational seminars and programs should be made mandatory, and the healthcare system should focus on high-risk individuals.

RSAD2, a pyroptosis-related gene, predicts the prognosis and immunotherapy response for colorectal cancer.

Colorectal cancer (CRC) is among the most prevalent malignant tumors, known for its high heterogeneity. Although many treatments and medications are available, the long-term survival rate of CRC patients is far from satisfactory. Pyroptosis is closely related to tumor progression. This study aimed to identify pyroptosis-related genes (PRGs) and candidate biomarkers to predict the prognosis of CRC patients. Used bioinformatics, we identified PRGs and subsequently screened 288 co-expression genes between pyroptosis-related modules and differentially expressed genes in CRC. Among these hub genes, we selected the top 24 for further analysis and found that Radical S-Adenosyl Methionine Domain Containing 2 (RSAD2) was a novel biomarker associated with the progression of CRC. We developed a risk model for RSAD2, which proved to be an independent prognostic indicator. The receiver operator characteristic analysis showed that the model had an acceptable prognostic value for patients with CRC. In addition, RSAD2 also affects the tumor immune microenvironment and prognosis of CRC. We further validated RSAD2 expression in CRC patients using RT-qPCR and the role of RSAD2 in pyroptosis. Taken together, this study comprehensively assessed the expression and prognostic value of RSAD2 in patients with CRC. These findings may offer a new direction for early CRC screening and development of future immunotherapy strategies.

Retracted: Functionalized Ferroferric Oxide Nanomagnetic Beads for Extraction of Nucleic Acid and Its Application in Early Screening of Colorectal Cancer.

[This retracts the article DOI: 10.1155/2021/5230666.].

Long-term benefits and harms of early colorectal cancer screening in German individuals with familial cancer risk.

Individuals with a family history of colorectal cancer (CRC) may benefit from early screening with colonoscopy or immunologic fecal occult blood testing (iFOBT). We systematically evaluated the benefit-harm trade-offs of various screening strategies differing by screening test (colonoscopy or iFOBT), interval (iFOBT: annual/biennial; colonoscopy: 10-yearly) and age at start (30, 35, 40, 45, 50 and 55 years) and end of screening (65, 70 and 75 years) offered to individuals identified with familial CRC risk in Germany. A Markov-state-transition model was developed and used to estimate health benefits (CRC-related deaths avoided, life-years gained [LYG]), potential harms (eg, associated with additional colonoscopies) and incremental harm-benefit ratios (IHBR) for each strategy. Both benefits and harms increased with earlier start and shorter intervals of screening. When screening started before age 50, 32-36 CRC-related deaths per 1000 persons were avoided with colonoscopy and 29-34 with iFOBT screening, compared to 29-31 (colonoscopy) and 28-30 (iFOBT) CRC-related deaths per 1000 persons when starting age 50 or older, respectively. For iFOBT screening, the IHBRs expressed as additional colonoscopies per LYG were one (biennial, age 45-65 vs no screening), four (biennial, age 35-65), six (biennial, age 30-70) and 34 (annual, age 30-54; biennial, age 55-75). Corresponding IHBRs for 10-yearly colonoscopy were four (age 55-65), 10 (age 45-65), 15 (age 35-65) and 29 (age 30-70). Offering screening with colonoscopy or iFOBT to individuals with familial CRC risk before age 50 is expected to be beneficial. Depending on the accepted IHBR threshold, 10-yearly colonoscopy or alternatively biennial iFOBT from age 30 to 70 should be recommended for this target group.

One-pot preparation of bi-functional POSS-based hybrid monolith via photo-initiated polymerization for isolation of extracellular vesicles

Extracellular vesicles (EVs) are important participants in numerous pathophysiological processes, and could be used as valuable biomarkers to detect and monitor various diseases. However, facile EV isolation methods are the essential and preliminary issue for their downstream analysis and function investigation. In this work, a polyhedral oligomeric silsesquioxanes (POSS) based hybrid monolith combined metal affinity chromatography (MAC) and distearoyl phospholipid ethanolamine (DSPE) function was developed via photo-initiated thiol-ene polymerization. This synthesis process was facile, simple and convenient, and the obtained hybrid monolith could be applied to efficiently isolate EVs from bio-samples by taking advantages of the specific bond of Ti4+ and phosphate groups on the phospholipid membrane of EVs and the synergistic effect of DSPE insertion. Meanwhile, the eluted EVs could maintain their structural integrity and biological activity, suggesting they could be used for downstream application. Furthermore, 75 up-regulated proteins and 56 down-regulated proteins were identified by comparing the urinary EVs of colorectal cancer (CRC) patients and healthy donors, and these proteins might be used as potential biomarkers for early screening of CRC. These results demonstrated that this hybrid monolith could be used as a simple and convenient tool for isolating EVs from bio-samples and for wider applications in biomarker discovery.

EVALUATION OF PUBLIC AWARENESS, KNOWLEDGE, AND ATTITUDES ABOUT COLORECTAL CANCER SCREENING AMONG THE GENERAL POPULATION IN AL-QUNFUDAH, SAUDI ARABIA

Colorectal cancer (CRC) is a malignant tumor of the colon and rectum. It can be cured if detected in the early stage through established screening programs. CRC screening is the best way to improve cancer morbidity and mortality. Various approaches such as stool tests, virtual colonoscopy, and sigmoidoscopy are available for early de- tection. On average, a person after reaching the age of 45 should begin the screening process for CRC periodically for 5 years. Our study aims to measure the populations awareness and knowledge of the effect of CRC screening on CRC outcomes. A cross-sectional study questionnaire was designed and distributed among Saudi residents of the Al-Qunfudah region. A total of 385 participants replied: 55.8% of the participants were males, 78.8% of the study participants mentioned that they had heard about CRC, and 27.3% reported that CRC is common in Al-Qunfudah. In addition, 62.1% knew that CRC is more common in men but only 32.2% had a good awareness level. Moreover, 16.4% of the participants reported that they had received a colonoscopy/sigmoidoscopy 69.9% did not think of the colonoscopy/sigmoidoscopy procedure as the main barrier to undergoing early screening for CRC. Good aware- ness regarding CRC was demonstrated in 34.4% of highly educated participants, which was directly associated with levels of education. In conclusion, much more awareness regarding CRC screening is needed in the Al-Qunfudah region. Educational seminars and programs should be made mandatory, and the healthcare system should focus on high-risk individuals.

RGSB-UNet: Hybrid Deep Learning Framework for Tumour Segmentation in Digital Pathology Images.

Colorectal cancer (CRC) is a prevalent gastrointestinal tumour with high incidence and mortality rates. Early screening for CRC can improve cure rates and reduce mortality. Recently, deep convolution neural network (CNN)-based pathological image diagnosis has been intensively studied to meet the challenge of time-consuming and labour-intense manual analysis of high-resolution whole slide images (WSIs). Despite the achievements made, deep CNN-based methods still suffer from some limitations, and the fundamental problem is that they cannot capture global features. To address this issue, we propose a hybrid deep learning framework (RGSB-UNet) for automatic tumour segmentation in WSIs. The framework adopts a UNet architecture that consists of the newly-designed residual ghost block with switchable normalization (RGS) and the bottleneck transformer (BoT) for downsampling to extract refined features, and the transposed convolution and 1 × 1 convolution with ReLU for upsampling to restore the feature map resolution to that of the original image. The proposed framework combines the advantages of the spatial-local correlation of CNNs and the long-distance feature dependencies of BoT, ensuring its capacity of extracting more refined features and robustness to varying batch sizes. Additionally, we consider a class-wise dice loss (CDL) function to train the segmentation network. The proposed network achieves state-of-the-art segmentation performance under small batch sizes. Experimental results on DigestPath2019 and GlaS datasets demonstrate that our proposed model produces superior evaluation scores and state-of-the-art segmentation results.