Early Diagnosis Of Colorectal Cancer Research Articles

Cell-free circulating tumor RNAs in plasma as the potential prognostic biomarkers in colorectal cancer.

Cell free RNA (cfRNA) contains transcript fragments from multiple cell types, making it useful for cancer detection in clinical settings. However, the pathophysiological origins of cfRNAs in plasma from colorectal cancer (CRC) patients remain unclear. To identify the tissue-specific contributions of cfRNAs transcriptomic profile, we used a published single-cell transcriptomics profile to deconvolute cell type abundance among paired plasma samples from CRC patients who underwent tumor-ablative surgery. We further validated the differentially expressed cfRNAs in 5 pairs of CRC tumor samples and adjacent tissue samples as well as 3 additional CRC tumor samples using RNA-sequencing. The transcriptomic component from intestinal secretory cells was significantly decreased in the in-house post-surgical cfRNA. The HPGD, PACS1, and TDP2 expression was consistent across cfRNA and tissue samples. Using the Cancer Genome Atlas (TCGA) CRC datasets, we were able to classify the patients into two groups with significantly different survival outcomes. The three-gene signature holds promise in applying minimal residual disease (MRD) testing, which involves profiling remnants of cancer cells after or during treatment. Biomarkers identified in the present study need to be validated in a larger cohort of samples in order to ascertain their possible use in early diagnosis of CRC.

Abstract 2302: Detection of tumor-associated methylation and mutation signatures for early colorectal cancer diagnosis

Abstract Introduction: The ability to identify epigenetic signatures, together with genetic alterations, has expanded the translational utility of genomic sequencing in clinical settings. Epigenetic changes may appear at very early stages before diagnosis. Thus, they could be used as epigenetic biomarkers for early detection or risk of cancer development. Circulating cell-free DNA (cfDNA) profiling has emerged as a promising biomarker for cancer diagnosis and prognosis. Herein, we developed targeted next-generation sequencing (NGS) based assays for assessing multiple DNA methylated and mutated regions in both low-quantity (plasma cfDNA) and low-quality formalin-fixed paraffin-embedded (FFPE) tissue for colorectal cancer (CRC) detection. Methods: For the OptiSeqTM CRC methylation panel, we assessed the methylation status of CpG dinucleotides in 42 genes. With this panel, we profiled 6 CRC samples (matching cfDNA and FFPE), 2 primary colon tumors with adjacent normal, and 6 advanced adenomas (AA) FFPE tissue DNA. For healthy individuals, we profiled 12 normal colon FFPE samples and 31 plasma cfDNA (26 matching buffy coat DNA samples). For the OptiSeqTM CRC mutation panel, the mutation status was assessed in 43 genes. Here, we profiled 6 CRC samples (matching cfDNA and FFPE), 19 CRC plasma cfDNA, 4 AA FFPE and 42 healthy individuals’ plasma cfDNA (26 matching buffy coat DNA samples). The analytical and clinical performance for both panels (separately and combined) were calculated using advanced adenoma (AA), CRC, and cancer-free individuals. Results: For CRC cfDNA samples, clinical samples testing showed that the methylation panel had a sensitivity of 50% (95% CI: 13.9-86.0) and specificity of 100% (95% CI: 86.2-100) while the mutation panel yielded the sensitivity 88% (95% CI: 67.7-96.8) and specificity 100% (95% CI: 89.5-100). Combining the mutation panel with the methylation panel, the sensitivity increased to 100% (95% CI: 51.6-100) and specificity to 100% (95% CI: 65.1-93.3). For AA FFPE samples, the methylation panel analysis yielded a sensitivity of 100% (95% CI: 39.5-100.0) and a specificity of 100% (95% CI: 67.8-100). Conclusion: We have developed and validated the targeted NGS-based panels to detect clinically relevant mutation and methylation patterns and demonstrate its potential as a highly sensitive assay for early CRC diagnosis. Citation Format: Pushpinder Bains, Mikhail Kulak, Zhen Cui, Alisha Babu, Stella Tran, Bongyong Lee, Aiguo Zhang, Michael Sha. Detection of tumor-associated methylation and mutation signatures for early colorectal cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2302.

Importance of the neutrophil-lymphocyte ratio and systemic immune-inflammation index in predicting colorectal pathologies in fecal occult blood-positive patients.

The fecal occult blood (FOB) test is one of the primary screening methods for colorectal cancer (CRC). In this study, we aimed to investigate the effect of the neutrophil/lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) in predicting CRC and other colorectal pathologies in patients with a positive FOB test. This retrospective study included patients with a positive FOB test who underwent colonoscopy for the investigation of the etiology. The optimal cutoff levels of NLR and SII for predicting colorectal pathologies were determined using the receiver operating characteristic analysis. Of the 157 FOB+ patients, 35% were male and 65% were female, with a median age of 59 years. There were 96 patients in Group 1 and 61 patients in Group 2. The mean age of the patients in Group 2 was significantly higher (p < 0.001). The rate of male patients was significantly higher in Group 2. NLR and SII were significantly higher in Group 2 than in Group 1 (p < 0.001). The area under the curve values of NLR and SII in predicting colorectal pathologies in FOB+ patients were 0.817 and 0.825, respectively. At the cutoff values of 0.689 and 0.795, NLR and SII had a sensitivity of 60.66% and 95.83%, respectively, and a specificity of 95.83% and 100%, respectively. Neutrophil/lymphocyte ratio and SII can be used as important biomarkers in the early diagnosis of CRC and other colorectal lesions in patients with a positive FOB test.

Neuroglobin plays as tumor suppressor by disrupting the stability of GPR35 in colorectal cancer

BackgroundThe incidence of colorectal cancer (CRC) has increased in recent years. Identification of accurate tumor markers has become the focus of CRC research. Early and frequent DNA methylation tends to occur in cancer. Thus, identifying accurate methylation biomarkers would improve the efficacy of CRC treatment. Neuroglobin (NGB) is involved in neurological and oncological diseases. However, there are currently no reports on epigenetic regulation involvement of NGB in CRC.ResultsNGB was downregulated or silenced in majority CRC tissues and cell lines. The hypermethylation of NGB was detected in tumor tissue, but no or a very low methylation frequency in normal tissues. Overexpression of NGB induced G2/M phase arrest and apoptosis, suppressed proliferation, migration, invasion in vitro, and inhibited CRC tumor growth and angiogenesis in vivo. Isobaric tag for relative and absolute quantitation (Itraq)-based proteomics identified approximately 40% proteins related to cell–cell adhesion, invasion, and tumor vessel formation in the tumor microenvironment, among which GPR35 was proved critical for NGB-regulated tumor angiogenesis suppression in CRC.ConclusionsNGB, an epigenetically silenced factor, inhibits metastasis through the GPR35 in CRC. It is expected to grow into a potential cancer risk assessment factor and a valuable biomarker for early diagnosis and prognosis assessment of CRC.

P53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins

Colorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer-related death worldwide. The detection in plasma samples of autoantibodies against specific tumor-associated antigens has been demonstrated to be useful for the early diagnosis of CRC by liquid biopsy. However, new studies related to the humoral immune response in cancer are needed to enable blood-based diagnosis of the disease. Here, our aim was to characterize the humoral immune response associated with the different p53 and p63 proteoforms derived from alternative splicing and previously described as aberrantly expressed in CRC. Thus, here we investigated the diagnostic ability of the twelve p53 proteoforms and the eight p63 proteoforms described to date, and their specific N-terminal and C-terminal end peptides, by means of luminescence HaloTag beads immunoassays. Full-length proteoforms or specific peptides were cloned as HaloTag fusion proteins and their seroreactivity analyzed using plasma from CRC patients at stages I-IV (n = 31), individuals with premalignant lesions (n = 31), and healthy individuals (n = 48). p53γ, Δ40p53β, Δ40p53γ, Δ133p53γ, Δ160p53γ, TAp63α, TAp63δ, ΔNp63α, and ΔNp63δ, together with the specific C-terminal end α and δ p63 peptides, were found to be more seroreactive against plasma from CRC patients and/or individuals with premalignant lesions than from healthy individuals. In addition, ROC (receiver operating characteristic) curves revealed a high diagnostic ability of those p53 and p63 proteoforms to detect CRC and premalignant individuals (AUC higher than 85%). Finally, electrochemical biosensing platforms were employed in POC-like devices to investigate their usefulness for CRC detection using selected p53 and p63 proteoforms. Our results demonstrate not only the potential of these biosensors for the simultaneous analysis of proteoforms' seroreactivity, but also their convenience and versatility for the clinical detection of CRC by liquid biopsy. In conclusion, we here show that p53 and p63 proteoforms possess differential seroreactivity in CRC patients in comparison to controls, distinctive from canonical proteins, which should improve the diagnostic panels for obtaining a blood-based biomarker signature for CRC detection.

Quantification of mitochondrial cfDNA reveals new perspectives for early diagnosis of colorectal cancer

BackgroundTo unravel how the integrity of nuclear and mitochondrial circulating cell-free DNA (cfDNA) contributes to its plasma quantity in colorectal cancer (CRC) patients.MethodsCfDNA from plasma samples of 80 CRC patients stratified by tumour stage and 50 healthy individuals were extracted. Total cfDNA concentration was determined and equal template concentrations (ETC) were analyzed by quantitative real-time PCR (qPCR) resulting in small and long fragments of KRAS, Alu and MTCO3. The obtained data was also examined relative to the total cfDNA concentration (NTC) and diagnostic accuracy was estimated using receiver operating characteristics.ResultsTotal cfDNA levels were significantly higher in CRC group compared to healthy control and increased with tumour stage. Long nuclear fragment levels were significantly lower in CRC patients in ETC but not NTC condition. The integrity indices of nuclear cfDNA decreased from controls to patients with highly malignant tumor. Mitochondrial cfDNA fragment quantities were strongly reduced in early and late stages of tumor patients and prognostic value was higher in ETC. Predictive models based on either ETC or NTC predictor set showed comparable classification performance.ConclusionIncreased blood cfDNA concentration in late UICC stages inversely correlate with nuclear cfDNA integrity index and suggest that necrotic degradation is not a major cause for higher total cfDNA quantity. The diagnostic and prognostic value of MTCO3 is highly significant in early stages of CRC and can be evaluated more comprehensively, using ETC for qPCR analysis.Trial registrationThe study was registered retrospectively on DRKS, the german register for clinical trials (DRKS00030257, 29/09/2022).

Uptake patterns and predictors of colorectal cancer screening among adults resident in Spain: A population-based study from 2017 to 2020.

Although population screening has improved the early diagnosis of colorectal cancer (CRC), most cases are diagnosed in symptomatic patients. This study aimed to estimate the prevalence and evolution over time of uptake patterns to fecal immunochemical test (FIT) as a screening test for CRC among individuals aged 50-69 in Spain, and to determine the predictive factors for uptake patterns to this type of screening based on sociodemographic, health, and lifestyle characteristics. A cross-sectional study with 14,163 individuals from the 2017 Spanish National Health Survey and the 2020 European Health Survey was performed, including as the main variable uptake pattern to FIT screening within the last 2 years, with which we analyzed sociodemographic factors, health status and lifestyle habits. 38.01% of participants had undergone FIT in the previous 2 years, and from 2017 to 2020, a significant increase in the uptake rate for CRC was observed (2017: 32.35%, 2020: 43.92%, p < 0.001). The positive predictors to FIT uptake pattern included factors such as being between 57 and 69 years, having a higher educational level or a higher social class, having at least one chronic illness, frequent contact with the primary care physician, alcohol consumption and physical activity, while immigration and smoking habit were negative predictors. In Spain, although the evolution of FIT uptake pattern over time is positive, the prevalence of FIT uptake is still low (38.01%), not reaching the level considered as acceptable in the European guidelines. Moreover, there are disparities in CRC screening uptake among individuals.

Differential methylation of DNA promoter sequences in peripheral blood mononuclear cells as promising diagnostic biomarkers for colorectal cancer.

Previous reports have indicated that the methylation profile in peripheral blood mononuclear cells (PBMCs) in different genes and loci is altered in colorectal cancer (CRC). Regarding the high mortality rate and silent nature of CRC, screening and early detection can meaningfully reduce disease-related deaths. Therefore, for the first time, we aimed to evaluate the early non-invasive diagnosis of CRC via quantitative promoter methylation analysis of RUNX3 and RASSF1A genes in PBMCs. In the present study, we analyzed the methylation status of two important tumor suppressor genes including RUNX3 and RASSF1A in 70 CRC patients and 70 non-malignant subjects using methylation-quantification of endonuclease-resistant DNA (MethyQESD), and a bisulfite conversion-independent method. RUNX3 was significantly hypermethylated in PBMCs of CRC patients compared to healthy controls (P < 0.001). By determining the efficient cutoff value, the sensitivity, and specificity of RUNX3 promoter methylation for CRC diagnosis reached 84.28% and 77.14%, respectively. The receiver operating characteristic (ROC) curve analyses demonstrated that RUNX3 promoter methylation has high accuracy (areas under the curve [AUC] = 0.840, P < 0.001) for discriminating CRC subjects from healthy individuals. Moreover, RUNX3 methylation levels in PBMCs progressively increased with the stage of the disease (P < 0.001). Although the amount of RASSF1A promoter methylation was not significantly different between CRC patients and controls as well as in different stages of the disease (P > 0.05). Our findings confirmed that PBMCs are reliable sources of methylation analysis for CRC screening, and RUNX3 promoter methylation can be used as a promising biomarker for early diagnosis of CRC.

Potential key genes are expected to become biomarker for early diagnosis of colorectal cancer through bioinformatics analysis

ABSTRACT Colorectal cancer (CRC) is the leading cause of cancer-related deaths in the world. The aim of this study was to identify the potential key genes, and associated pathways for early-onset CRC through bioinformatics methods. We integrated the gene expression patterns of CRC from three RNAseq datasets (GSE8671, GSE20916, GSE39582) from GEO database to identify DEGs between CRC and normal samples. We established a gene co-expression network through WGCNA. Through the WGCNA calculation, the genes were divided into six modules. The WGCNA analysis screened 242 genes associated with pathological stage and colorectal adenocarcinoma, 31 of which had the ability to predict OS with an AUC >0.7. The GSE39582 dataset identified 2040 DEGs between the CRC and normal samples. The two were intersected to obtain two genes: NPM1 and PANK3. The two genes were used as a threshold to divide the samples into high group and low group for survival analysis. Survival analysis showed that increased expression of both genes was significantly associated with a poorer prognosis. These two genes (NPM1 and PANK3) could be possible marker genes for early diagnosis of CRC, providing ideas for other experimental studies in the future.

Safety and efficacy comparison of polyethylene glycol, hemp seed oil, and 5% sugar brine for bowel preparation in older patients: study protocol for a randomized controlled trial

BackgroundThe incidence of colorectal cancer among the middle-aged and elderly is gradually increasing in China. Colonoscopy is an effective method for the early diagnosis of colorectal cancer, and bowel preparation is one of many important factors affecting colonoscopy. Although there are many studies on intestinal cleansers, the results are not ideal. There is evidence that hemp seed oil has certain potential effects in intestinal cleansing, but prospective studies on this topic are still lacking.MethodsThis is a randomized, double-blind, single-center clinical study. We randomly assigned 690 participants to groups each administered 3 L of polyethylene glycol (PEG), 30 mL of hemp seed oil and 2 L of PEG, or 30 mL of hempseed oil, 2 L of PEG, and 1000 mL of 5% sugar brine. The Boston Bowel Preparation Scale was considered the primary outcome measure. We evaluated the interval between consumption of bowel preparation and first bowel movement. Secondary indicators included the time of cecal intubation, detection rate of polyps and adenomas, willingness to repeat the same bowel preparation, whether the protocol was tolerated, and whether there were adverse reactions during bowel preparation and were evaluated after counting the total number of bowel movements.DiscussionThis study aimed to test the hypothesis that hemp seed oil (30 mL) increases the quality of bowel preparation and reduces the amount of PEG. Previously, we found that its combination with 5% sugar brine can reduce the occurrence of adverse reactions.Trial registrationChinese Clinical Trial Registry ChiCTR2200057626. Prospectively registered on March 15, 2022

Non-steroidal anti-inflammatory drugs and biomarkers: A new paradigm in colorectal cancer.

Colorectal cancer is a sporadic, hereditary, or familial based disease in its origin, caused due to diverse set of mutations in large intestinal epithelial cells. Colorectal cancer (CRC) is a common and deadly disease that accounts for the 4th worldwide highly variable malignancy. For the early detection of CRC, the most common predictive biomarker found endogenously are KRAS and ctDNA/cfDNA along with SEPT9 methylated DNA. Early detection and screening for CRC are necessary and multiple methods can be employed to screen and perform early diagnosis of CRC. Colonoscopy, an invasive method is most prevalent for diagnosing CRC or confirming the positive result as compared to other screening methods whereas several non-invasive techniques such as molecular analysis of breath, urine, blood, and stool can also be performed for early detection. Interestingly, widely used medicines known as non-steroidal anti-inflammatory drugs (NSAIDs) to reduce pain and inflammation have reported chemopreventive impact on gastrointestinal malignancies, especially CRC in several epidemiological and preclinical types of research. NSAID acts by inhibiting two cyclooxygenase enzymes, thereby preventing the synthesis of prostaglandins (PGs) and causing NSAID-induced apoptosis and growth inhibition in CRC cells. This review paper majorly focuses on the diversity of natural and synthetic biomarkers and various techniques for the early detection of CRC. An approach toward current advancement in CRC detection techniques and the role of NSAIDs in CRC chemoprevention has been explored systematically. Several prominent governing mechanisms of the anti-cancer effects of NSAIDs and their synergistic effect with statins for an effective chemopreventive measure have also been discussed in this review paper.

Exploring Core Genes by Comparative Transcriptomics Analysis for Early Diagnosis, Prognosis, and Therapies of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers with a high mortality rate. Early diagnosis and therapies for CRC may reduce the mortality rate. However, so far, no researchers have yet investigated core genes (CGs) rigorously for early diagnosis, prognosis, and therapies of CRC. Therefore, an attempt was made in this study to explore CRC-related CGs for early diagnosis, prognosis, and therapies. At first, we identified 252 common differentially expressed genes (cDEGs) between CRC and control samples based on three gene-expression datasets. Then, we identified ten cDEGs (AURKA, TOP2A, CDK1, PTTG1, CDKN3, CDC20, MAD2L1, CKS2, MELK, and TPX2) as the CGs, highlighting their mechanisms in CRC progression. The enrichment analysis of CGs with GO terms and KEGG pathways revealed some crucial biological processes, molecular functions, and signaling pathways that are associated with CRC progression. The survival probability curves and box-plot analyses with the expressions of CGs in different stages of CRC indicated their strong prognostic performance from the earlier stage of the disease. Then, we detected CGs-guided seven candidate drugs (Manzamine A, Cardidigin, Staurosporine, Sitosterol, Benzo[a]pyrene, Nocardiopsis sp., and Riccardin D) by molecular docking. Finally, the binding stability of four top-ranked complexes (TPX2 vs. Manzamine A, CDC20 vs. Cardidigin, MELK vs. Staurosporine, and CDK1 vs. Riccardin D) was investigated by using 100 ns molecular dynamics simulation studies, and their stable performance was observed. Therefore, the output of this study may play a vital role in developing a proper treatment plan at the earlier stages of CRC.

A Novel Approach on the Use of Samples from Faecal Occult Blood Screening Kits for Metabolomics Analysis: Application in Colorectal Cancer Population.

The incidence of colorectal cancer (CRC) is increasing, and currently it is the third most common cancer. Early CRC diagnosis is still difficult and relies on an invasive colonoscopy and tissue biopsy. The globally observed tendency demands non-invasive, specific, and accurate diagnostic tools for early diagnosis and prognosis. In this work, the main aim was to evaluate for the first time the feasibility of using extracts from the non-invasive sample collection from faecal occult blood (FOB) kits for its use in metabolomics studies taking advantage in this way of the high sensitivity of this technology. Then, a cohort of 131 samples from control individuals (CTL), adenoma (AD) and CRC patients were analysed using a semitargeted approach by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry (UHPLC-ToF-MS). Multivariate and univariate statistical analysis revealed that cholesteryl esters (ChoE) with polyunsaturated fatty acids (PUFAs) together with FOB were relevant metabolites that could clearly separate CRC patients from AD and CTL individuals, whereas the metabolic profiles of CTL and AD were very similar. These results are in agreement with previous findings and reveal the advantage of using the same FOBT samples for several analyses, which would facilitate sample collection and improve direct connection between FOB measurements and metabolomics analysis. Although the sample size and the number of metabolites should be enhanced to cover a wider range of metabolites, alterations in lipid metabolism clearly point out for future perspectives.

Optimized transfer learning for polyp detection

Early diagnosis of colorectal cancer focuses on detecting polyps in the colon as early as possible so that patients can have the best chances for success- ful treatment. This research presents the optimized parameters for polyp detection using a deep learning technique. Polyp and non-polyp images are trained on the InceptionResnetV2 model by the Faster Region Con- volutional Neural Networks (Faster R-CNN) framework to identify polyps within the colon images. The proposed method revealed more remarkable results than previous works, precision: 92.9 %, recall: 82.3%, F1-Measure: 87.3%, and F2-Measure: 54.6% on public ETIS-LARIB data set. This detection technique can reduce the chances of missing polyps during a pro- longed clinical inspection and can improve the chances of detecting multiple polyps in colon images.

Novel DNA methylation biomarkers in stool and blood for early detection of colorectal cancer and precancerous lesions

BackgroundEarly detection and prevention of precancerous lesions can significantly reduce the morbidity and mortality of colorectal cancer (CRC). Here, we developed new candidate CpG site biomarkers for CRC and evaluated the diagnostic value of their expression in blood and stool samples of CRC and precancerous lesions.MethodsWe analyzed 76 pairs of CRC and adjacent normal tissue samples, 348 stool samples, and 136 blood samples. Candidate biomarkers for CRC were screened using a bioinformatics database and identified using a quantitative methylation-specific PCR method. The methylation levels of the candidate biomarkers were validated using blood and stool samples. The divided stool samples were used to construct and validate a combined diagnostic model and to analyze the independent or combined diagnostic value of candidate biomarkers in stool samples of CRC and precancerous lesions.ResultsTwo candidate CpG site biomarkers for CRC, cg13096260 and cg12993163, were identified. Although both biomarkers demonstrated diagnostic performance to a certain extent when using blood samples, they showed better diagnostic value for different stages of CRC and AA with stool samples.Conclusionscg13096260 and cg12993163 detection in stool samples could be a promising approach for screening and early diagnosis of CRC and precancerous lesions.

Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer.

Exosomes are promising new biomarkers for colorectal cancer (CRC) diagnosis, due to their rich biological fingerprints and high level of stability. However, the accurate detection of exosomes with specific surface receptors is limited to clinical application. Herein, an exosome enrichment platform on a 3D porous sponge microfluidic chip is constructed and the exosome capture efficiency of this chip is ≈90%. Also, deep mass spectrometry analysis followed by multi-level expression screenings revealed a CRC-specific exosome membrane protein (SORL1). A method of SORL1 detection by specific quantum dot labeling is further designed and the ensemble classification system is established by extracting features from 64-patched fluorescence images. Importantly, the area under the curve (AUC) using this system is 0.99, which is significantly higher (p< 0.001) than that using a conventional biomarker (carcinoembryonicantigen(CEA), AUC of 0.71). The above system showed similar diagnostic performance, dealing with early-stage CRC, young CRC, and CEA-negative CRC patients.

Application of Polypyrrole-Based Electrochemical Biosensor for the Early Diagnosis of Colorectal Cancer

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

A Reliable and Sensitive Framework for Simultaneous Type and Stage Detection of Colorectal Cancer Polyps.

With the goal of enhancing the early diagnosis of colorectal cancer (CRC) polyps and reducing the risk of mortality in cancer patients, in this article, we present a unique diagnosis framework including a Vision-based Surface Tactile Sensor (VS-TS) and complementary Artificial Intelligence algorithms. Leveraging the morphological characteristics (i.e., shape and texture) and stiffness features of the CRC polyps, the proposed framework is able to reliably and sensitively identify their type and stage. To thoroughly characterize and identify the required VS-TS sensitivity for reliable identification of polyps, we first fabricated three different VS-TSs and qualitatively evaluated their performances on 48 different types of polyp phantoms fabricated based on four different types of realistic CRC polyps and three different materials. Next, to quantitatively compare the performance and sensitivity of the fabricated VS-TSs, we used Support Vector Machine (SVM) algorithm and employed various statistical metrics (i.e., accuracy, reliability, and sensitivity). Next, using the most sensitive VS-TS, we classified the type of tumors using the SVM algorithm and applied the t-Distributed Stochastic Neighbor Embedding algorithm to successfully identify the stiffness of classified polyp phantoms solely based on the output images of the VS-TS sensor. Results demonstrated that an SVM algorithm applied on the image outputs of a VS-TS with a Shore hardness of 00-40 scale is able to classify all types of polyps with > 90% accuracy, sensitivity, and reliability. We also repeated experiments on samples of ex-vivo lamb tripe tissues and successfully verified the high sensitivity and reliability of the proposed framework (i.e., > 94%).

Mean platelet volume/platelet count ratio in combination with tumor markers in colorectal cancer: a retrospective clinical study

BackgroundMean platelet volume (MPV) is a marker of platelet activation, which is usually negatively correlated with platelet count (PC). The ratio of MPV to PC (MPV/PC) has an essential role in the diagnosis of multiple malignancies. However, only a few studies investigated the value of MPV/PC in colorectal cancer (CRC) and the combination of MPV/PC with tumor markers in CRC. This retrospective clinical study aimed to evaluate the diagnostic value of MPV/PC and tumor markers (CA72-4, CA125, CA199) used alone or in combination in CRC.Methods200 patients with CRC and 317 patients with colorectal benign polypus pathologically diagnosed during 2019/01/04 to 2022/06/30 were included. Hematological and pathological parameters of the above patients were collected, data were analyzed with Student’s t-test, one-way ANOVA or Kruskal-Wallis H test and receiver operating characteristic (ROC) curve, and ROC curve was used to evaluate the diagnostic value of tumor markers and MPV/PC used alone or in combination in CRC.ResultsThe MPV/PC in CRC group was significantly lower than the control group (P < 0.0001). Among the three tumor markers, higher CA125 was correlated with distant metastasis and lower differentiation (P < 0.05), increased CA72-4 indicated positive nerve invasion (P = 0.0174), and elevated CA199 was associated with lymphatic metastasis and positive vascular invasion (P < 0.05). For subgroups regarding tumor anatomical location, both CA125 and CA199 were higher in colon cancer group than rectum cancer group (P = 0.0322, P = 0.0094). MPV/PC was associated with tumor infiltration, regional lymph node metastasis, differentiation and nerve invasion (P < 0.05) and the combination of MPV/PC with the three tumor markers produced a larger AUC with higher sensitivity, specificity and Yuden index than MPV/PC or the three tumor markers used alone to distinguish between CRC and colorectal polyps.ConclusionPreoperative MPV/PC in peripheral blood of patients with CRC was lower than the control group. Meanwhile, the combined detection of tumor markers with MPV/PC can improve the diagnostic value of CRC, revealing the potential of MPV/PC as a promising screening tool in CRC early diagnosis.

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.