Early Diagnosis Of Colorectal Cancer Research Articles

A Panel of Four Anti-HSPG Monoclonal Antibodies Benefits in Increasing the Specificity in Detection of Colorectal Cancer

Colorectal cancer (CRC) is the second leading with main cause of death is liver and lung metastasis. Using of a combination of genetic and epigenetic markers are addressed but the results have not been approved in clinical practice. A set of serum biomarkers has been proposed to increase accuracy in early diagnosis of CRC. In addition, non-invasive as well as the best prognostic panel of biomarkers and define predictive biomarkers for treatment of CRC are all aims of future research. HSPGs is an important biomolecule involving in cancer cell proliferation, differentiation, and migration. Membrane HSPGs shed into blood circulation and matrix in particular circumstance can be used as a specific biomarker for some cancer cells. In order to evaluate the benefit of a panel of anti-HSPGs monoclonal antibodies in increasing specificity to detect CRC, four clones of anti-HSPGs were studied for its specific reaction on various tumor cell lines by indirect immunofluorescent technique and analyzed by flow cytometer compared to normal white blood cells. A combination of two or more clones were focused. The results showed that all four clones presented a variation in reaction to all solid tumor cell lines tested but negative to normal white blood cells from different ABO blood groups. Interestingly, amongst those cells tested, HT29, a colorectal cancer cell lines were significantly reacted with all four monoclonal antibodies. Taken together, we proposed a panel of four anti-HSPGs monoclonal antibodies to be applied in various detection platforms to increase the specificity in screening of CRC. Keywords: Cancer biomarkers, Colorectal cancer, HSPG

A diagnostic prediction model for colorectal cancer in elderlies via internet of medical things.

Internet of Medical Things (IoMT) and embedded systems have improved the healthcare systems by enabling remote monitoring the patients’ health conditions anywhere and anytime especially during novel COVID-19 pandemic. In this paper, an IoT-based predicting model is proposed to predict colorectal cancer (CRC) in elderlies. It provides a CRC predicting model for the involved medical team to continuously trace an elderly’s biological indicators using smart wearable embedded systems and medical IoT devices. In this model, vital medical data is collected by IoMT devices and sensors, then analytical information is derived via machine learning (ML) methods for early CRC diagnosis and elderly’s health parameters changes. The experimental results confirm that the suggested model meets the proper accuracy of predicting the CRC in aged people.

Comprehensive aptamer-based screen of 1317 proteins uncovers improved stool protein markers of colorectal cancer.

To screen and validate novel stool protein biomarkers of colorectal cancer (CRC). A novel aptamer-based screen of 1317 proteins was used to uncover elevated proteins in the stool of patients with CRC, as compared to healthy controls (HCs) in a discovery cohort. Selected biomarker candidates from the discovery cohort were ELISA validated in three independent cross-sectional cohorts comprises 76 CRC patients, 15 adenoma patients, and 63 healthy controls, from two different ethnicities. The expression of the potential stool biomarkers within CRC tissue was evaluated using single-cell RNA-seq datasets. A total of 92 proteins were significantly elevated in CRC samples as compared to HCs in the discovery cohort. Among Caucasians, the 5 most discriminatory proteins among the 16 selected proteins, ordered by their ability to distinguish CRC from adenoma and healthy controls, were MMP9, haptoglobin, myeloperoxidase, fibrinogen, and adiponectin. Except myeloperoxidase, the others were significantly associated with depth of tumor invasion. The 8 stool proteins with the highest AUC values were also discriminatory in a second cohort of Indian CRC patients. Several of the stool biomarkers elevated in CRC were also expressed within CRC tissue, based on the single-cell RNA-seq analysis. Stool MMP9, fibrinogen, myeloperoxidase, and haptoglobin emerged as promising CRC stool biomarkers, outperforming stool Hemoglobin. Longitudinal studies are warranted to assess the clinical utility of these novel biomarkers in early diagnosis of CRC.

Morden tactic in diagnosis and treatment of early colon cancer (review of literature)

According to the literature review, the use of modern endoscopes with high resolution and a narrow-band imagine function with optical magnification, as well as autofluorescence, chromoscopy, endosonography, makes it possible to establish a diagnosis of early colorectal cancer with a high degree of accuracy. Nowadays, endoscopic submucosal dissection and endoscopic mucosal resection are the methods of choice in the treatment of early (Tis, T1sm1N0M0) colon cancer.

Circulating Biomarkers of Colorectal Cancer (CRC)-Their Utility in Diagnosis and Prognosis.

The global burden of colorectal cancer (CRC) is expected to increase, with 2.2 million new cases and 1.1 million annual deaths by 2030. Therefore, the establishment of novel biomarkers useful in the early diagnosis of CRC is of utmost importance. A number of publications have documented the significance of the overexpression of several specific proteins, such as inflammatory mediators, in CRC progression. However, little is known about the potential utility of these proteins as circulating blood tumor biomarkers of CRC. Therefore, in the present review we report the results of our previous original studies as well as the findings of other authors who investigated whether inflammatory mediators might be used as novel biomarkers in the diagnosis and prognosis of CRC. Our study revealed that among all of the tested proteins, serum M-CSF, CXCL-8, IL-6 and TIMP-1 have the greatest value in the diagnosis and progression of CRC. Serum TIMP-1 is useful in differentiating between CRC and colorectal adenomas, whereas M-CSF and CRP are independent prognostic factors for the survival of patients with CRC. This review confirms the promising significance of these proteins as circulating biomarkers for CRC. However, due to their non-specific nature, further validation of their sensitivity and specificity is required.

Identification of microbial markers across populations in early detection of colorectal cancer

Associations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-l-glycero-beta-d-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.

Reconstrução de Trânsito Intestinal: Caracterização sociodemográfica, clínica e terapêutica da clientela

Objetivo: Analisar as características sociodemográficas, clínicas e terapêuticas de pessoas submetidas à Reconstrução de Trânsito Intestinal. Metodologia: trata-se de um estudo retrospectivo, descritivo-analítico, quantitativo, realizado em um centro de reabilitação especializado em uma cidade paulista, com levantamento de 134 prontuários de pacientes que realizaram Reconstrução de Trânsito Intestinal (RTI), aprovado pelo Comitê de Ética em Pesquisa (Parecer nº 2.831.709). Resultados e discussão: Com a análise de prontuários da população de pacientes que realizaram RTI 134 (100%), obteve-se média de idade de 57,3 anos, predominantemente do sexo masculino 78 (58%), do atendimento pelo sistema público de saúde 122 (91%); do diagnóstico oncológico 63 (47%); de cirurgia de urgência 88 (66%); e de 92 (69%) pessoas com colostomias. Houve correlação estatisticamente significante entre tipo de estomia, caráter da cirurgia, técnica cirúrgica e o diagnóstico de indicação cirúrgica, diferentemente das variáveis cirurgia e o tempo de estomia. Conclusão: Há necessidade de prevenção e diagnóstico precoce de CCR, além do planejamento da assistência à saúde para o seguimento de controle cirúrgico e oncológico, para agilização de reconstrução de trânsito intestinal (RTI) quando possível, além do preparo desta clientela para as mudanças na vida após RTI, bem como no gerenciamento da previsão e provisão de equipamentos coletores e adjuvantes, o que requer integração das ações dos diferentes níveis de atendimento desta clientela.

A NOVEL EXTENSIVE EX-VIVO OCT DATABASE FROM MURINE MODELS OF COLORECTAL CANCER

Abstract INTRODUCTION New non-invasive technologies for improving early diagnosis of colorectal cancer (CRC) are demanded by clinicians. Optical Coherence Tomography (OCT) provides sub-surface structural information and offers diagnosis capabilities of colon polyps, further improved by machine learning methods. Databases of OCT images are necessary to facilitate algorithms development and testing. MATERIALS AND METHODS A database has been acquired from rat colonic samples with a Thorlabs OCT system with 930nm centre wavelength that provides 1.2KHz A-scan rate, 7μm axial resolution in air, 4μm lateral resolution, 1.7mm imaging depth in air, 6mm x 6mm FOV, and 107dB sensitivity. The colon from anaesthetised animals has been excised and samples have been extracted and preserved for ex-vivo analysis with the OCT equipment. RESULTS This database consists of OCT 3D volumes (C-scans) and 2D images (B-scans) of murine samples from: 1) healthy tissue, for ground-truth comparison (18 samples; 66 C-scans; 17,478 B-scans); 2) hyperplastic polyps, obtained from an induced colorectal hyperplastic murine model (47 samples; 153 C-scans; 42,450 B-scans); 3) neoplastic polyps (adenomatous and adenocarcinomatous), obtained from clinically validated Pirc F344/NTac-Apcam1137 rat model (232 samples; 564 C-scans; 158,557 B-scans); and 4) unknown tissue (polyp adjacent, presumably healthy) (98 samples; 157 C-scans; 42,070 B-scans). CONCLUSIONS A novel extensive ex-vivo OCT database of murine CRC model has been obtained and will be openly published for the research community. It can be used for classification/segmentation machine learning methods, for correlation between OCT features and histopathological structures, and for developing new non-invasive in-situ methods of diagnosis of colorectal cancer.

ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer.

Simple SummaryThe survival of colorectal cancer patients largely relies on the stage at diagnosis. The identification of early and non-invasive biomarkers to be used in screening programs for the diagnosis of the disease at the premalignant stage is mandatory. The aim of this study is to validate in plasma-derived extracellular vesicles secreted by malignant cells the diagnostic potential of well-known tumor-associated genes, ΔNp73, TAp73, and Δ133p53, in healthy subjects (n = 29), individuals with premalignant lesions (n = 49), and colorectal cancer patients (n = 42). Our data support ΔNp73 levels contained in extracellular vesicles as such a non-invasive and premature biomarker for the early diagnosis of colorectal cancer.The early diagnosis of colorectal cancer is a key factor in the overall survival of the patients. The actual screening programs include different approaches with significant limitations such as unspecificity, high invasiveness, and detection at late stages of the disease. The specific content of extracellular vesicles derived from malignant cells may represent a non-invasive technique for the early detection of colorectal cancer. Here, we studied the mRNA levels of ΔNp73, TAp73, and Δ133p53 in plasma-derived extracellular vesicles from healthy subjects (n = 29), individuals with premalignant lesions (n = 49), and colorectal cancer patients (n = 42). Extracellular vesicles’ ΔNp73 levels were already significantly high in subjects with premalignant lesions. Δ133p53 levels were statistically increased in colorectal cancer patients compared to the other two groups and were associated with patients’ survival. Remarkably, TAp73 mRNA was not detected in any of the individuals. The evaluation of ΔNp73, Δ133p53 and CEA sensitivity, specificity and AUC values supports ΔNp73 as a better early diagnosis biomarker and CEA as the best to identify advanced stages. Thus, low levels of CEA and a high content of ΔNp73 may identify in screening programs those individuals at higher risk of presenting a premalignant lesion. In addition, Δ133p53 emerges as a potential prognosis biomarker in colorectal cancer.

Clinical Assay for the Early Detection of Colorectal Cancer Using Mass Spectrometric Wheat Germ Agglutinin Multiple Reaction Monitoring.

Simple SummaryColorectal cancer (CRC) is currently the third leading cause of cancer death worldwide. Early diagnosis of CRC is important for increasing the opportunity for treatment and receiving a good prognosis. The aim of our study was to develop a detection method that combined wheat germ agglutinin (WGA) chromatography with mass spectrometry (MS) for early detection of CRC. Further, machine learning algorithms and logistic regression were applied to combine multiple biomarkers we discovered. We validated in a population of 286 plasma samples the diagnostic performance of peptides corresponding to WGA-captured protein and its combination, which received a sensitivity of 84.5% and a specificity of 97.5% in the diagnoses of CRC. Proteomic biomarkers combined with algorithms can provide a powerful tool for discriminating patients with CRC and health controls (HCs). Measurements of WGA-captured PF4, ITIH4, and APOE with MS are then useful for early detection of CRC. Additionally, our study revealed the potential of applying lectin chromatography with MS for disease diagnosis.Colorectal cancer (CRC) is currently the third leading cause of cancer-related mortality in the world. U.S. Food and Drug Administration-approved circulating tumor markers, including carcinoembryonic antigen, carbohydrate antigen (CA) 19-9 and CA125 were used as prognostic biomarkers of CRC that attributed to low sensitivity in diagnosis of CRC. Therefore, our purpose is to develop a novel strategy for novel clinical biomarkers for early CRC diagnosis. We used mass spectrometry (MS) methods such as nanoLC-MS/MS, targeted LC-MS/MS, and stable isotope-labeled multiple reaction monitoring (MRM) MS coupled to test machine learning algorithms and logistic regression to analyze plasma samples from patients with early-stage CRC, late-stage CRC, and healthy controls (HCs). On the basis of our methods, 356 peptides were identified, 6 differential expressed peptides were verified, and finally three peptides corresponding wheat germ agglutinin (WGA)-captured proteins were semi-quantitated in 286 plasma samples (80 HCs and 206 CRCs). The novel peptide biomarkers combination of PF454–62, ITIH4429–438, and APOE198–207 achieved sensitivity 84.5%, specificity 97.5% and an AUC of 0.96 in CRC diagnosis. In conclusion, our study demonstrated that WGA-captured plasma PF454–62, ITIH4429–438, and APOE198–207 levels in combination may serve as highly effective early diagnostic biomarkers for patients with CRC.

Assessing Colorectal Cancer Screening Barriers in Rural Appalachia

The age-appropriate colorectal cancer (CRC) screening rate in the rural Appalachian area is low compared with the national rate, which may account for the overall higher incidence of CRC in this area. The purpose of this study was to explore potential barriers to CRC screening in the West Virginia Appalachian area. A cross-sectional survey was designed to identify patient-reported barriers to CRC screening using the health belief model to assess their attitudes and behaviors. Autonomous paper-based surveys were randomly handed to individuals older than 50 years at various locations, including healthcare and nonhealthcare facilities. All of the responses were then categorized into two groups: the screened group and the unscreened group. Differences among both groups were statistically analyzed. There were three main areas that significantly accounted for the discrepancies between the screened and unscreened groups: perceptions of discomfort from screening tests, psychological and behavior deterrents in CRC screening and diagnosis, and limited resources for accessing care, especially transportation. In particular, psychological and behavioral deterrents in CRC screening appeared to play a role in promoting aversion to CRC screening. Lack of CRC screening awareness and knowledge may be responsible for fatalism regarding CRC and aversion to screening. Thus, multidisciplinary interventions that provide education about CRC screening, early intervention prognosis, and treatment options, as well as addressing systemic barriers to screening, such as assistance with scheduling, prep instructions, and transportation, can improve the screening rate in Appalachia and eventually lead to better outcomes through the early diagnosis of CRC.

Advances in Imaging Modalities and Contrast Agents for the Early Diagnosis of Colorectal Cancer.

Colorectal cancer is one of the most common gastrointestinal cancers worldwide. The mortality rate of colorectal cancer has declined by more than 20% due to the rapid development of early diagnostic techniques and effective treatment. At present, there are many diagnostic modalities available for the evaluation of colorectal cancer, such as the carcinoembryonic antigen test, the fecal occult blood test, endoscopy, X-ray barium meal, computed tomography, magnetic resonance imaging, and radionuclide examination. Sensitive and specific imaging modalities have played an increasingly important role in the diagnosis of colorectal cancer following the rapid development of novel contrast agents. This review discusses the applications and challenges of different imaging techniques and contrast agents applied to detect colorectal cancer, for the purpose of the early diagnosis and treatment of patients with colorectal cancer.

Clinical Value of Detecting Tumor Endothelial Marker 8 (ANTXR1) as a Biomarker in the Diagnosis and Prognosis of Colorectal Cancer.

BackgroundDespite the continuous improvements in prevention and detection of colorectal cancer (CRC), there is an urgent need to find a sensitive, specific, and noninvasive biomarker to improve the early diagnosis and prognosis of CRC. We aimed to evaluate the tissue TEM8 expression and the serum TEM8 concentration in CRC patients.MethodsThe study enrolled 42 CRC patients and 35 controls. Immunohistochemical staining was performed to assess the TEM8 tissue expression, whereas the serum TEM8 concentration was evaluated with the ELISA assay.ResultsThe expression of TEM8 observed in all primary colorectal tumor samples was significantly correlated with the TNM stages and the presence of lymphovascular invasion. The serum TEM8 concentration was significantly higher in CRC patients than in the controls. The TEM8 level was strongly associated with the TNM stage, depth of invasion, and lymph node and distant metastasis. Patients with a high serum TEM8 concentration had a worse overall survival (OS) rate than CRC patients with a low serum TEM8 level.ConclusionTEM8 may serve as a biomarker for the diagnosis of CRC and it has value in predicting the prognosis of patients with CRC.

The Roles of Transmembrane Mucins Located on Chromosome 7q22.1 in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common types of cancers. It is associated with a poor prognosis and high mortality. The role of mucins (MUCs) in colon tumorigenesis is unclear, but it might be significant in the progression of malignancy. Some mucins, such as MUC1 and MUC13, act as oncogenes, whereas others, such as MUC2 and MUC6, are tumor suppressors. However, there are still mucins with unidentified roles in CRC. In this review, we discuss the reported roles of mucins in CRC. Moreover, we review the capability of the mucin family to serve as a sensitive and specific histopathological marker for the early diagnosis of CRC. Lastly, the role of mucin genes clustered on chromosome 7q22 in CRC and other cancers is also discussed.

Development of a Novel Prognostic Model for Predicting Lymph Node Metastasis in Early Colorectal Cancer: Analysis Based on the Surveillance, Epidemiology, and End Results Database.

BackgroundIdentification of a simplified prediction model for lymph node metastasis (LNM) for patients with early colorectal cancer (CRC) is urgently needed to determine treatment and follow-up strategies. Therefore, in this study, we aimed to develop an accurate predictive model for LNM in early CRC.MethodsWe analyzed data from the 2004-2016 Surveillance Epidemiology and End Results database to develop and validate prediction models for LNM. Seven models, namely, logistic regression, XGBoost, k-nearest neighbors, classification and regression trees model, support vector machines, neural network, and random forest (RF) models, were used.ResultsA total of 26,733 patients with a diagnosis of early CRC (T1) were analyzed. The models included 8 independent prognostic variables; age at diagnosis, sex, race, primary site, histologic type, tumor grade, and, tumor size. LNM was significantly more frequent in patients with larger tumors, women, younger patients, and patients with more poorly differentiated tumor. The RF model showed the best predictive performance in comparison to the other method, achieving an accuracy of 96.0%, a sensitivity of 99.7%, a specificity of 92.9%, and an area under the curve of 0.991. Tumor size is the most important features in predicting LNM in early CRC.ConclusionWe established a simplified reproducible predictive model for LNM in early CRC that could be used to guide treatment decisions. These findings warrant further confirmation in large prospective clinical trials.

A novel cell-free DNA methylation-based model improves the early detection of colorectal cancer.

Screening for early‐stage disease is vital for reducing colorectal cancer (CRC)‐related mortality. Methylation of circulating tumor DNA has been previously used for various types of cancer screening. A novel cell‐free DNA (cfDNA) methylation‐based model which can improve the early detection of CRC is warranted. For our study, we collected 313 tissue and 577 plasma samples from patients with CRC, advanced adenoma (AA), non‐AA and healthy controls. After quality control, 187 tissue DNA samples (91 non‐malignant tissue from CRC patients, 26 AA and 70 CRC) and 489 plasma cfDNA samples were selected for targeted DNA methylation sequencing. We further developed a cfDNA methylation model based on 11 methylation biomarkers for CRC detection in the training cohort (area under curve [AUC] = 0.90 (0.85–0.94]) and verified the model in the validation cohort (AUC = 0.92 [0.88–0.96]). The cfDNA methylation model robustly detected patients pre‐diagnosed with early‐stage CRC (AUC = 0.90 [0.86–0.95]) or AA (AUC = 0.85 [0.78–0.91]). Here we established and validated a non‐invasive cfDNA methylation model based on 11 DNA methylation biomarkers for the detection of early‐stage CRC and AA. The utilization of the model in clinical practice may contribute to the early diagnosis of CRC.

Hsa_circ_001659 serves as a novel diagnostic and prognostic biomarker for colorectal cancer

Colorectal cancer (CRC) is prevalent worldwide and novel diagnostic and prognostic biomarkers are needed to improve precision medicine. Circular RNAs (circRNAs) are currently being considered as emerging tumor biomarkers. Herein, we aimed to explore the possible clinical application of circRNAs in the early diagnosis and prognostic prediction of CRC. First, candidate circRNA was selected by integrating analysis of Gene Expression Omnibus (GEO) database using GEO2R program. ROC curve analysis demonstrated the predictive values and likelihood ratios of circ_001659 were satisfactory for the diagnosis of CRC, including patients in early-stage disease or patients with carcinoembryonic antigen (CEA)-negative status. Moreover, serum circ_001659 may be a novel biomarker in the assessment of successful treatment and remission of cancer tracking. We further investigated the oncogenic role of circ_001659. In vivo and in vitro experiments indicated that circ_001659 could promote CRC cell invasion and migration. Mechanistically, circ_001659 was localized in the nucleus, recruited the RBBP5 to Vimentin promoter and increased H3K4 trimethylation level on the Vimentin promoter region, which epigenetically activated Vimentin transcription. Our findings demonstrate that circ_001659 could be a useful serum biomarker for CRC diagnosis and prognosis. Targeting circ_001659 and its pathway may be meaningful for treating patients with CRC.

RNAM EXPRESSION AND DNA METHYLATION OF DKK2 GENE IN COLORECTAL CÂNCER.

Colorectal cancer is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of colorectal cancer remains unclear. The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. Among the 35 patients studied, 18 were male, 10 were on right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 expression and clinical or pathological features. DKK2 promoter methylation (P=0.154) and DKK2 RNA expression (P=0.345) did not show significant correlation with overall survival. DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.

Aberrant expression of m6A mRNA methylation regulators in colorectal adenoma and adenocarcinoma

BackgroundAs the most prevalent post-transcriptional mRNA modification in eukaryotes, N6-Methyladenosine (m6A) is closely linked to the occurrence and development of colorectal cancer (CRC). However, there is no systematic evaluation of the expression of m6A regulatory genes in CRC. MethodsBy analyzing the TCGA database, we identified METTL3, YTHDF1, IGF2BP1, IGF2BP3, EIF3B, HNRNPA2B1 as overexpressed m6A regulators in CRC. After verification by immunohistochemistry (IHC) in 10 CRC cases, YTHDF1, IGF2BP1, IGF2BP3, and EIF3B were identified as potential biomarkers in CRC. Further validation was done by IHC and qRT-PCR in two larger cohorts. ResultsWe identified 6 up-regulated m6A regulatory genes in CRC in TCGA analysis, and verified that YTHDF1, IGF2BP1, IGF2BP3, and EIFB3 were all significantly differentially expressed between CRC and normal tissues by IHC (p < 0.0001). In another larger cohort, we further validated the overexpression of those genes in CRC as compared to both normal tissues (p < 0.0001) and adenoma tissues (p < 0.05). Detailed analysis suggested that detection of one of the three genes, YTHDF1, IGF2BP1 and IGF2BP3, and combined detection of EIF3B gene could be a good strategy for early diagnosis of both CRC and precancerous lesions. Furthermore, we found that the mRNA levels of YTHDF1, IGF2BP1, and IGF2BP3 were also significantly up-regulated in CRC but not adenoma as compared to normal tissues. ConclusionWe evaluted the abnormal expression of m6A regulatory genes during CRC carcinogenesis, and identified four m6A genes (YTHDF1, IGF2BP1, IGF2BP3, and EIF3B) as potential biomarkers of both CRC and adenoma.

Identification of ANXA1 as a potential prognostic biomarker and correlating with immune infiltrates in colorectal cancer

Background ANXA1 is a calcium-dependent phospholipid-binding protein and is frequently associated with inflammation, cell proliferation and apoptosis. However, the relationship between ANXA1 and the prognosis of multiple tumours and tumour infiltrating immune cells remains unclear. Methods Multivariate Cox proportional regression analysis was used for signature genes exploration in the basic of colon adenocarcinoma (COAD) RNA-sequence dataset obtained from TCGA, following the identification of 267 common differentially expressed genes, including ANXA1, among three expression profile datasets (GSE41328, GSE110224, and GSE113513). The differential expression of ANXA1 in different tumours and their corresponding normal tissues were evaluated through the Tumour Immune Estimation Resource (TIMER) and Oncomine database. Subsequently, we investigated the correlation between the expression level of ANXA1 and diverse panel of infiltrating immune cells and their related gene markers in colorectal cancer using correlation analysis in TIMER and GEPIA database. Results The high expression of ANXA1 was demonstrated to be closely correlated with poor survival in patients with colorectal cancer. More importantly, we found that changes in ANXA1 expression showed a moderate to strong, and statistically significant, correlation with infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. By contrast, there are only weak correlations between ANXA1 expression and immune cell infiltration in ESCA and STAD. ANXA1 expression was considerably associated with various immune markers involving immune cell recruitment, polarization of tumour-associated macrophages, and T cell exhaustion. Conclusion ANXA1 is not only an independent risk factor in the prediction of the prognosis of colorectal cancer, but also a crucial regulator in immune cell infiltration. This study may shed light on the clinical value of ANXA1, especially in the areas of early diagnosis of colorectal cancer and therapeutic target discovery.