Early Diagnosis Of Colorectal Cancer Research Articles

Faecal microbial biomarkers in early diagnosis of colorectal cancer.

Colorectal cancer (CRC) is ranked as the second most common cause of cancer deaths and the third most common cancer globally. It has been described as a ‘silent disease’ which is often easily treatable if detected early—before progression to carcinoma. Colonoscopy, which is the gold standard for diagnosis is not only expensive but is also an invasive diagnostic procedure, thus, effective and non‐invasive diagnostic methods are urgently needed. Unfortunately, the current methods are not sensitive and specific enough in detecting adenomas and early colorectal neoplasia, hampering treatment and consequently, survival rates. Studies have shown that imbalances in such a relationship which renders the gut microbiota in a dysbiotic state are implicated in the development of adenomas ultimately resulting in CRC. The differences found in the makeup and diversity of the gut microbiota of healthy individuals relative to CRC patients have in recent times gained attention as potential biomarkers in early non‐invasive diagnosis of CRC, with promising sensitivity, specificity and even cost‐effectiveness. This review summarizes recent studies in the application of these microbiota biomarkers in early CRC diagnosis, limitations encountered in the area of the faecal microbiota studies as biomarkers for CRC, and future research exploits that address these limitations.

Deep learning driven colorectal lesion detection in gastrointestinal endoscopic and pathological imaging.

Colorectal cancer has the second highest incidence of malignant tumors and is the fourth leading cause of cancer deaths in China. Early diagnosis and treatment of colorectal cancer will lead to an improvement in the 5-year survival rate, which will reduce medical costs. The current diagnostic methods for early colorectal cancer include excreta, blood, endoscopy, and computer-aided endoscopy. In this paper, research on image analysis and prediction of colorectal cancer lesions based on deep learning is reviewed with the goal of providing a reference for the early diagnosis of colorectal cancer lesions by combining computer technology, 3D modeling, 5G remote technology, endoscopic robot technology, and surgical navigation technology. The findings will supplement the research and provide insights to improve the cure rate and reduce the mortality of colorectal cancer.

Automatic Polyp and InstrumentSegmentation in MedAI-2021

Polyp and instrument segmentation plays a vital role in the early diagnosis of colorectal cancer (CRC) in that physicians visually inspect the bowel with an endoscope to identify polyps. However, recent works only focus on the accuracy of prediction in the positive samples while omitting the False-Positive (FP) predictions in the negative samples that might mislead the physicians. Here, we propose a novel Dual Model Filtering (DMF) strategy, which efficiently removes FP predictions in negative samples with metrics based threshold setting. To better adapt high-resolution input with various distributions, we embed the PVTv2 backbone to the framework SINetV2 as our model since the polyp segmentation is one of the downstream tasks of camouflaged object detection (COD). Experiments on challenging MedAI datasets demonstrate our method achieves excellent performance. We also conduct extensive experiments to study the effectiveness of the DMF.

Targeted Bisulfite Sequencing Reveals DNA Methylation Changes in Zinc Finger Family Genes Associated With KRAS Mutated Colorectal Cancer.

Background: Colorectal cancer (CRC) is a leading cause of cancer death, and early diagnosis of CRC could significantly reduce its mortality rate. Previous studies suggest that the DNA methylation status of zinc finger genes (ZFGs) could be of potential in CRC early diagnosis. However, the comprehensive evaluation of ZFGs in CRC is still lacking.Methods: We first collected 1,426 public samples on genome-wide DNA methylation, including 1,104 cases of CRC tumors, 54 adenomas, and 268 para-tumors. Next, the most differentially methylated ZFGs were identified and validated in two replication cohorts comprising 218 CRC patients. Finally, we compared the prediction capabilities between the ZFGs and the SEPT9 in all CRC patients and the KRAS + and KRAS- subgroup.Results: Five candidate ZFGs were selected: ESR1, ZNF132, ZNF229, ZNF542, and ZNF677. In particular, ESR1 [area under the curve (AUC) = 0.91] and ZNF132 (AUC = 0.93) showed equivalent or better diagnostic capability for CRC than SEPT9 (AUC = 0.91) in the validation dataset, suggesting that these two ZFGs might be of potential for CRC diagnosis in the future. Furthermore, we performed subgroup analysis and found a significantly higher diagnostic capability in KRAS + (AUC ranged from 0.97 to 1) than that in KRAS- patients (AUC ranged from 0.74 to 0.86) for all these five ZFGs, suggesting that these ZFGs could be ideal diagnostic markers for KRAS mutated CRC patients.Conclusion: The methylation profiles of the candidate ZFGs could be potential biomarkers for the early diagnosis of CRC, especially for patients carrying KRAS mutations.

TP1.2.7The stuck colonoscope

Abstract Background With the increased awareness and push for earlier diagnosis of colorectal cancer, the number of patients undergoing colonoscopy is increasing. Being a common condition, a number of these patients will have herniae. We describe a rare complication during a Sigmoidoscopy in a patient with an Inguinal hernia. The case A 75-year-old man was booked for a flexible sigmoidoscopy for rectal bleeding. The scope was successfully inserted to the Splenic flexure. During withdrawal, the scope stopped moving. It was still possible to advance the scope, but not to withdraw. The patient confirmed the presence of a left inguinal hernia. Physical examination and the position on magnetic scope imager confirmed the loop in the hernia. Various manoeuvres to withdraw the scope were unsuccessful. A colleague was called for a second opinion. We came up with a plan to maintain a ‘long loop‘ position in the hernia, by holding the scope through the scrotum and allowing it to slide on withdrawal. This was successful and the patient was discharged. Discussion Incarceration of the scope in the hernia occurs when the hernial defect permits entry and exit of the scope, leaving a loop in the hernia, in a long loop position. During withdrawal, the configuration changes to a short loop, crowding the hernial defect, preventing the scope from sliding. On searching literature, we found that this technique has been described by Koltun et al and is known as the “Pulley” technique. We suggest that colonoscopists are familiar with this technique.

BH-index: A predictive system based on serum biomarkers and ensemble learning for early colorectal cancer diagnosis in mass screening

Background and objective: Colorectal cancer is one of the most common malignancies among the general population. Artificial Intelligence methodologies based on serum parameters are in continuous development to obtain less expensive tools for highly sensitive diagnoses. This study proposes a predictive system based on serum biomarkers and ensemble learning to predict colorectal cancer presence and the related TNM stage in patients.Methods: We have selected 17 significant plasmatic proteins, i.e., Carcinoembryonic Antigen, CA 19-9, CA 125, CA 50, CA 72-4, Tissue Polypeptide Antigen, C-Reactive Protein, Ceruloplasmin, Haptoglobin, Transferrin, Ferritin, α-1-Antitrypsin, α-2-Macroglobulin, α-1 Acid Glycoprotein, Complement C4, Complement C3, and Retinol Binding Protein, regarding 345 patients (248 affected by the neoplastic disease). The proposed system consists of two predictors, i.e., binary and staging; the former predicts the presence/absence of cancer, while the latter identifies the related TNM stage (I, II, III, or IV). The experiments were conducted by deploying and comparing Random Forest, XGBoost, Support Vector Machine, and Multilayer Perceptron with feature selection based on Gini Importance and with dimensionality reduction via PCA.Results: The results show that the system composed of XGBoost as binary and staging predictor reaches 91.30% accuracy, 90% sensitivity, and 93.33% specificity for the absence/presence outcome, while 66.66% accuracy for the staging response. With the expansion of the training set in favor of positive patients and majority voting, the system composed of the combination of Support Vector Machine, XGBoost, and Multilayer Perceptron as the binary predictor reaches 98.03% accuracy, 100% sensitivity, and 92.30% specificity, while the combination of Random Forest, XGBoost, and Multilayer Perceptron as staging predictor achieves 60% accuracy. The final system reaches, in terms of accuracy, 98.03%, and 66.66% for the binary and staging predictors, respectively. It was also found that the biomarkers which contribute most to the binary decision are Ceruloplasmin and α-2-Macroglobulin, while the least significant dimensions are CA 50 and α-1-Antitrypsin; instead, Carcinoembryonic Antigen and α-1 Acid Glycoprotein are the most significant to the staging decision.Conclusions: The present study proves the effectiveness of deploying serum biomarkers as feature dimensions for early colorectal cancer diagnosis and of using majority voting for noise reduction in the prediction.

MicroRNAs: Small molecules with a large impact on colorectal cancer.

Colorectal cancer (CRC) accounts for one of the main cancer-related mortality and morbidity worldwide. The molecular mechanisms of CRC development have been broadly investigated and, over the last decade, it has become evident that aberrant transcription of microRNAs (miRNAs), a class of small, noncoding RNA molecules, has a significant role in the inception and promotion of CRC. In the involved tissues of CRC, the transcription profile of miRNAs is modulated, and their expression templates are related with prognosis, diagnosis, and treatment outcomes. Here, in the current review, we attempted to discuss the latest information regarding the aberrantly expressed miRNAs in CRC and the advantages of utilizing miRNAs as biomarkers for early diagnosis and prognosis of CRC as well as potential therapeutic application. The effect of miRNAs involved in various signaling pathways, primarily p53, EGFR, Wnt, and TGF-β pathways, was clarified.

Multiplexed DNA Methylation Analysis in Colorectal Cancer Using Liquid Biopsy and Its Diagnostic and Predictive Value.

Early diagnosis of colorectal cancer (CRC) is of high importance as prognosis depends on tumour stage at the time of diagnosis. Detection of tumour-specific DNA methylation marks in cfDNA has several advantages over other approaches and has great potential for solving diagnostic needs. We report here the identification of DNA methylation biomarkers for CRC and give insights in our methylation-sensitive restriction enzyme coupled qPCR (MSRE-qPCR) system. Targeted microarrays were used to investigate the DNA methylation status of 360 cancer-associated genes. Validation was done by qPCR-based approaches. A focus was on investigating marker performance in cfDNA from 88 patients (44 CRC, 44 controls). Finally, the workflow was scaled-up to perform 180plex analysis on 110 cfDNA samples, to identify a DNA methylation signature for advanced colonic adenomas (AA). A DNA methylation signature (n = 44) was deduced from microarray experiments and confirmed by quantitative methylation-specific PCR (qMSP) and by MSRE-qPCR, providing for six genes’ single areas under the curve (AUC) values of >0.85 (WT1, PENK, SPARC, GDNF, TMEFF2, DCC). A subset of the signatures can be used for patient stratification and therapy monitoring for progressed CRC with liver metastasis using cfDNA. Furthermore, we identified a 35-plex classifier for the identification of AAs with an AUC of 0.80.

Colorectal Cancer in Uganda: A 10-Year, Facility-Based, Retrospective Study.

IntroductionColorectal cancer (CRC) is the most common type of gastrointestinal malignancies and the third leading cause of cancer-related deaths for both sexes worldwide. Although the burden of CRC is highest in developed countries, reports are indicating a rise in the incidence of early-onset CRC in developing countries. In this study, we aimed to determine the prevalence of CRC among patients hospitalized with lower gastrointestinal complaints at a tertiary health facility in Uganda.MethodsWe conducted a 10-year retrospective chart review of patients admitted to Mulago National Referral Hospital in Kampala, Uganda, between 1st January 2010 and 31st December 2020. We reviewed all charts of patients admitted to the lower gastrointestinal tract (GIT) ward. Charts with grossly missing data, pediatric patients, and those from other non-lower GIT specialties were excluded.ResultsData of 1476 unique eligible patients were analyzed. Of these,138 had a diagnosis of CRC (prevalence: 9.3%, 95% confidence interval (95% CI): 6.5–11.7%). Among patients with CRC, the female:male ratio was 1:1. The most common site for CRC was the rectum (59.8%, n= 79). For the 138 participants with CRC, 44 had staging data with 72.8% (n=32) having advanced disease, that is, stage 3 or 4. Factors independently associated with CRC were age ≥50 years (adjusted odds ratio (aOR): 4.3, 95% CI: 2.6–7.1, p < 0.001), female sex (aOR: 1.8, 95% CI: 1.2 −2.8, p = 0.005), being widowed (aOR: 2.5, 95% CI: 1.3–5.0, p = 0.006), and presence of any risk factor for CRC (aOR: 5.3, 95% CI: 2.9–9.9, p < 0.001).ConclusionCRC is relatively common among patients hospitalized with lower GIT complaints, particularly among women and those with known risk factors for CRC. Awareness creation and screening programs should be instituted to allow early diagnosis of CRC in our setting.

Interleukin-38 Suppresses Cell Migration and Proliferation and Promotes Apoptosis of Colorectal Cancer Cell Through Negatively Regulating Extracellular Signal-Regulated Kinases Signaling.

Inflammatory cytokines has been of great interest in the field of colorectal cancer (CRC) tumor immunology in recent years. As an anti-inflammatory interleukin (IL), IL-38 may contribute to the early diagnosis of CRC and improve the prognosis of CRC patients. This study was designed to investigate the role of circulating IL-38 and the regulatory mechanism of IL-38 in CRC. Expression of IL-38 were detected by ELISA and immunohistochemical staining. The influence of IL-38 on CRC were evaluated by Western blot and cell biology assays after CRC cells were treated by rhIL-38 or LM22B-10. We also verified the anti-tumor activity of IL-38 in transgenic mouse model. The expression of IL-38 was found to be correlated with progression of CRC. IL-38 inhibits CRC metastasis, proliferation and facilitates apoptosis through suppressing the activation of extracellular signal-regulated kinases (ERK) signaling pathway inducing the decrease of downstream genes, which were partially abrogated by ERK activator LM22B-10 in vitro. We also found that IL-38 overexpression inhibits tumorigenesis in vivo. Our findings indicate that IL-38 may serve as a serum prediction marker to identify the prognosis of CRC patients. IL-38 may inhibit the progression of CRC by negatively regulation on ERK signaling pathway.

Nanotechnology in Colorectal Cancer for Precision Diagnosis and Therapy

Colorectal cancer (CRC) is the third most frequently occurring tumor in the human population. CRCs are usually adenocarcinomatous and originate as a polyp on the inner wall of the colon or rectum which may become malignant in the due course of time. Although the therapeutic options of CRC are limited, the early diagnosis of CRC may play an important role in preventive and therapeutic interventions to decrease the mortality rate. The CRC-affected tissues exhibit several molecular markers that may be exploited as the novel strategy to develop newer approaches for the treatment of the disease. Nanotechnology consists of a wide array of innovative and astonishing nanomaterials with both diagnostics and therapeutic potential. Several nanomaterials and nano formulations such as Carbon nanotubes, Dendrimer, Liposomes, Silica Nanoparticles, Gold nanoparticles, Metal-organic frameworks, Core-shell polymeric nano-formulations, Nano-emulsion System, etc can be used to targeted anticancer drug delivery and diagnostic purposes in CRC. The light-sensitive photosensitizer drugs loaded gold and silica nanoparticles can be used to diagnose as well as the killing of CRC cells by the targeted delivery of anticancer drugs to cancer cells. This review is focused on the recent advancement of nanotechnology in the diagnosis and treatment of CRC.

CRISPR/Cas13-Based Platforms for a Potential Next-Generation Diagnosis of Colorectal Cancer through Exosomes Micro-RNA Detection: A Review.

Simple SummaryColorectal cancer is one of the most prevalent cancers, whereas a significant number of cases are diagnosed in late cancer stages, and survival rates drop dramatically. Micro-RNAs (miRNAs) from cancer-derived exosomes have shown promising diagnosis potential. Our review aims to present CRISPR/Cas-based molecular platforms as an inexpensive, swift, and robust detection tool of cancer-derived exosome micro-RNAs to streamline future applications based on the novel CRISPR/Cas-based platforms to achieve early CRC diagnosis.Colorectal cancer (CRC) is the third most prevalent cancer with the second highest mortality rate worldwide. CRC is a heterogenous disease with multiple risk factors associated, including obesity, smoking, and use of alcohol. Of total CRC cases, 60% are diagnosed in late stages, where survival can drop to about 10%. CRC screening programs are based primarily on colonoscopy, yet this approach is invasive and has low patient adherence. Therefore, there is a strong incentive for developing molecular-based methods that are minimally invasive and have higher patient adherence. Recent reports have highlighted the importance of extracellular vesicles (EVs), specifically exosomes, as intercellular communication vehicles with a broad cargo, including micro-RNAs (miRNAs). These have been syndicated as robust candidates for diagnosis, primarily for their known activities in cancer cells, including immunoevasion, tumor progression, and angiogenesis, whereas miRNAs are dysregulated by cancer cells and delivered by cancer-derived exosomes (CEx). Quantitative polymerase chain reaction (qPCR) has shown good results detecting specific cancer-derived exosome micro-RNAs (CEx-miRNAs) associated with CRC, but qPCR also has several challenges, including portability and sensitivity/specificity issues regarding experiment design and sample quality. CRISPR/Cas-based platforms have been presented as cost-effective, ultrasensitive, specific, and robust clinical detection tools in the presence of potential inhibitors and capable of delivering quantitative and qualitative real-time data for enhanced decision-making to healthcare teams. Thereby, CRISPR/Cas13-based technologies have become a potential strategy for early CRC diagnosis detecting CEx-miRNAs. Moreover, CRISPR/Cas13-based platforms’ ease of use, scalability, and portability also showcase them as a potential point-of-care (POC) technology for CRC early diagnosis. This study presents two potential CRISPR/Cas13-based methodologies with a proposed panel consisting of four CEx-miRNAs, including miR-126, miR-1290, miR-23a, and miR-940, to streamline novel applications which may deliver a potential early diagnosis and prognosis of CRC.

Evaluation of colonoscopic findings in patients undergoing colonoscopy due to positive fecal occult blood test: a single center experience

Aim: Fecal occult blood test is used in the early diagnosis of colorectal cancers. We aimed to evaluate the colonoscopic and pathological findings of patients who underwent colonoscopy due to positive fecal occult blood test in a tertiary center.&#x0D; Material and Method: Patients who had a positive fecal occult blood test and referred to the xxx Training and Research Hospital endoscopy unit for colonoscopy were included in this study. Age, gender, colonoscopic findings and pathology results of the patients were recorded. Statistical analyzes were performed with SPSS.&#x0D; Results: Two hundred and twenty three patients were included in the current study. Of the patients, 101 (45.3%) were male and 122 (54.7%) were female, with a mean age of 53.2 (18-90 years). Endoscopic diagnoses were as 49 (22%) polyps, 13 (5.8%) colon cancer, 4 (1.8%) inflammatory bowel disease, 15 (6.7%) diverticulum, 63 (28.3%) perianal disease, 79 (35.4%) normal colonoscopic findings. Pathological features of colon polyps were as; tubular adenoma in 51%, tubulovillous adenoma in 18.4%, serrated adenoma in 2%, and hyperplastic polyp in 28.6%. Colonoscopy findings of patients according to age groups (over and under 50 years of age); the incidence of polyps (p=0.01) and diverticulum (p=0.001) were significantly higher in patients older than 50 years, while perianal diseases (p=0.031) and normal colonoscopic findings (p=0.008) were higher in patients younger than 50 years of age.&#x0D; Conclusion: Colon pathology was detected in approximately 2/3 of the patients presenting with a positive fecal occult blood test. This test is an inexpensive, easily applicable method that helps to detect colon cancer and precursor lesions, as well as pathologies such as subclinical inflammatory bowel disease and diverticulum causing chronic blood loss.

Expression profiles of miR-196, miR-132, miR-146a, and miR-134 in human colorectal cancer tissues in accordance with their clinical significance : Comparison regarding KRAS mutation.

Colorectal cancer (CRC) is among the most widespread malignancies in the world. MicroRNA (miRNA) has been identified as an important modulator of the biological processes of the cells. This group of noncoding RNAs also has apivotal function in the growth and development of human cancers, including CRC. Among these miRNAs, miR-196, miR-132, miR-146a, and miR-134 have fundamental impacts on the regulation of cancers. The current study aimed to investigate the involvement of these miRNAs in CRC patients. In this study, 50pairs of tumor and tumor margin samples of CRC patients were investigated to assess the expression levels of miR-196, miR-132, miR-146a, and miR-134 in this cancer. For this purpose, firstly, quantitative real-time PCR (qRT-PCR) was applied. Also, KRAS mutation and clinicopathological characteristics of the CRC patients were analyzed in the study groups. The findings demonstrated the overexpression of miR-196 (P-value = 0.0045) and miR-146a (P-value = 0.0033) in tumor tissues compared to controls. Conversely, the expression levels of miR-132 (P-value = 0.00032) and miR-134 (P-value < 0.0001) were downregulated in tumor tissues. Also, miR-146a was the only miRNA with significant expression change in the case of the KRAS gene mutation. Interestingly, the expression ratio of these miRNAs was significantly associated with some of the clinicopathological features of the patients, such as lymph node and distant metastases. Our data demonstrated that these miRNAs appear to be promising novel biomarkers for early diagnosis of CRC and may pave the way for the future establishment of novel therapeutic options for CRC.

Depth diagnosis of early colorectal cancer: Magnifying chromoendoscopy or image enhanced endoscopy with magnification?

Depth diagnosis is extremely crucial in making a treatment choice between endoscopic resection and surgery in the early stages of cancers. Among several imaging modalities, we use magnifying endoscopy to diagnose lesions by close observation of the findings at mucosal surface layer. In combination with topical staining, magnifying endoscopy enables us to assess the definite pit structure, which referred to as magnifying chromoendoscopy (MCE). The pit pattern classification by MCE was proposed and is now widely accepted as the standard diagnostic criteria for colorectal lesions. Meanwhile, image enhanced endoscopy (IEE) represented by narrow-band imaging was developed to improve the visibility of surface and vascular findings without dyeing. Recent collaborative work performed by endoscopic experts in Japan yielded the unified diagnostic criteria, the Japan NBI Expert Team (JNET) classification, based on the findings of IEE with magnification. In this review, focusing on MCE and IEE with magnification, we aimed to give an outline of the pit pattern classification and the JNET classification, and further discuss their accuracy rate of depth diagnosis of early colorectal lesions by performing a review of the related literature. Both modalities have a high accuracy rate of nearly 90% for depth diagnosis. IEE with magnification is an ideal modality because it helps observe lesions without dye spraying; however, lesions with JNET type 2B have an inadequate diagnostic ability, which should be complemented by MCE. We conclude that accurate diagnosis is possible by examining lesions using both modalities properly to overcome the limitations of each modality.

Evaluation of Colon-Specific Plasma Nanovesicles as New Markers of Colorectal Cancer.

Simple SummaryHigh mortality in patients with colorectal cancer (CRC) is one of the main problems in healthcare. This is due to the use of invasive and existing noninvasive screening methods whose resources are limited. A promising alternative is a study of circulating in plasma extracellular nanovesicles (ENVs) reflecting the same composition of biomarkers with the secreted cells, forming subpopulations of tissue-specific ENVs. During the work, we have selected potential colon biomarkers from databases. The study aims to develop a quantitative method for isolating colon-specific ENVs based on the formation of immunocomplexes «beads with antibodies to specific biomarkers». We found that the amount of ENVs carrying potential colon biomarkers was higher in the patients with an IV CRC-stage compared with the healthy donors. It showed a high coefficient of diagnostic significance of these biomarkers in the CRC prognosis. These results will give an impetus to a deeper study of the ENVs as identifiers of cancer’s development.Purpose: Developing new and efficient approaches for the early diagnosis of colorectal cancer (CRC) is an important issue. Circulating extracellular nanovesicles (ENVs) present a promising class of cancer markers. Cells of well-differentiated adenocarcinomas retain the molecular characteristics of colon epithelial cells, and the ENVs secreted by these cells may have colon-specific surface markers. We hypothesize that an increase in the number of ENVs carrying colon-specific markers could serve as a diagnostic criterion for colorectal cancer. Experimental design: Potential colon-specific markers were selected based on tissue-specific expression profile and cell surface membrane localization data. Plasma was collected from CRC patients (n = 48) and healthy donors (n = 50). The total population of ENVs was isolated with a two-phase polymer system. ENVs derived from colon epithelium cells were isolated using immune-beads with antibodies to colon-specific markers prior to labelling with antibodies against exosomal tetraspanins (CD63 and CD9) and quantification by flow cytometry. Results: The number of ENVs positive for single colon cancer markers was found to be significantly higher in the plasma of CRC patients compared with healthy donors. The efficacy of detection depends on the method of ENV labelling. The diagnostic efficacy was estimated by ROC analysis (the AUC varied between 0.71 and 0.79). The multiplexed isolation of colon-derived ENVs using immune-beads decorated with antibodies against five markers allowed for a further increase in the diagnostic potency of the method (AUC = 0.82). Conclusions: ENVs derived from colon epithelium may serve as markers of differentiated CRC (adenocarcinomas). The composition of ligands used for capturing colon-derived ENVs and their method of labelling are critical for the efficacy of this proposed diagnostic approach.

Gankyrin as Potential Biomarker for Colorectal Cancer With Occult Liver Metastases.

The majority of occult liver metastases cannot be detected by computed tomography (CT), magnetic resonance imaging (MRI) or other traditionally morphological imaging approaches since the lesions are too small or they have not yet formed cancer nodules. Gankyrin is a small molecular protein composed of seven ankyrin domains. In this study, the expression of Gankyrin in colorectal cancer (CRC) patients with liver metastases was investigated to determine its prognosis value. Gankyrin expression in CRC patients was initially analyzed using data from The Cancer Genome Atlas (TCGA) database and bioinformatics tools. RT-qPCR, western blotting, immunohistochemistry (IHC) and transwell migration and invasion assays were then performed to verify the expression and function of Gankyrin in CRC cell line, CRC tissues and matched non-tumor tissues of clinical patients. General clinicopathological information including TNM stage as well as preoperative and postoperative imaging results were collected. The main outcome indicator was overall survival (OS), referring to the length of time from surgery to either death or the last visit. Statistical analyses included chi-squared tests, Cox analyses, progression free survival (PFS) rates and OS rates. Elevated Gankyrin expression was confirmed in CRC patients. The upregulated Gankyrin expression was positively correlated with the progression of disease and liver metastasis in CRC patients. OS analysis revealed that prognosis was worse in CRC patients with high Gankyrin expression compared to those with low expression. CRC patients with higher Gankyrin expression also had a higher risk of occult liver metastases and a lower PFS rate. Therefore, Gankyrin can be used as a potential biomarker for early diagnosis of CRC with occult liver metastasis.

B-PO02-147 IMPACT OF ORAL ANTICOAGULATION THERAPY ON COLORECTAL CANCER DIAGNOSIS

Oral anticoagulation therapy (AC) is associated with an increased risk of gastrointestinal (GI) bleeding which is frequently the presenting symptom of colorectal cancer (CRC). There is currently no evidence that AC is associated with an earlier diagnosis of CRC. We sought to investigate if GI bleeding on AC leads to earlier diagnosis of CRC. We retrospectively reviewed pathology findings from 417 patients with CRC undergoing tumor resection. Data was analyzed by tumor greatest dimension, histopathology grade and TNM system. Data was then compared by AC and anti-platelet therapy (AP) use at the time of tumor resection. At time of diagnosis, 27 patients were on AC (6.5%, DOAC n=20, Warfarin n=7) and 390 patients were not. Patients on AC had smaller tumor size (3.3 ± 1.3 cm) vs. those not on AC (4.3 ± 2.7cm, p= 0.02). Of 27 patients on AC, only 2 (8%) were diagnosed ≥ tumor stage 4 compared to 72/374 patients not on AC (19%, p= 0.125). Distant metastasis was found in 5/27 patients (19%) on AC vs. 122/388 patients not on AC (31%, p=0.4). AP therapy was not associated with a decrease in tumor size or stage at diagnosis. AC use was associated with smaller tumor size at the time of diagnosis with a trend toward less advanced tumor stage. Earlier diagnosis of CRC may lead to earlier treatment and improved mortality. Further studies are needed to determine whether AC use is associated with lower mortality in this patient population.

Determination of VOCs in Surgical Resected Tissues from Colorectal Cancer Patients by Solid Phase Microextraction Coupled to Gas Chromatography–Mass Spectrometry

Early diagnosis of colorectal cancer is crucial to increase the survival rates of the patients and breath analysis represents a promising non-invasive tool to obtain information on cancer-related variations on the human volatilome. A solid phase microextraction coupled to gas chromatography–mass spectrometry method for the determination of seven selected compounds, representative of the volatilome secreted by the colonic mucosa of patients affected by colorectal cancer, including benzaldehyde, benzoic acid, dodecane, ethylbenzene, octanal, tetradecane and toluene, was developed. All the extraction parameters were studied for both headspace and direct immersion sampling and the procedures fully validated. The potential of the approach was demonstrated by the time monitoring of the emission of the selected volatile organic compounds from the surgical resected colon mucosa tissues of colorectal cancer patients. Furthermore, the extraction and identification of thirty-one volatile organic compounds secreted by the same tissues was accomplished.

Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers.

Despite advances in the characterization of colorectal cancer (CRC), it still faces a poor prognosis. There is growing evidence that gut microbiota and their metabolites potentially contribute to the development of CRC. Thus, microbial dysbiosis and their metabolites associated with CRC, based on stool samples, may be used to advantage to provide an excellent opportunity to find possible biomarkers for the screening, early detection, prevention, and treatment of CRC. Using 16S rRNA amplicon sequencing coupled with statistical analysis, this study analyzed the cause–effect shift of the microbial taxa and their metabolites that was associated with the fecal gut microbiota of 17 healthy controls, 21 polyps patients, and 21 cancer patients. The microbial taxonomic shift analysis revealed striking differences among the healthy control, polyps and cancer groups. At the phylum level, Synergistetes was reduced significantly in the polyps group compared to the healthy control and cancer group. Additionally, at the genus level and in association with the cancer group, a total of 12 genera were highly enriched in abundance. In contrast, only Oscillosprira was significantly higher in abundance in the healthy control group. Comparisons of the polyps and cancer groups showed a total of 18 significantly enriched genera. Among them, 78% of the genera associated with the cancer group were in higher abundance, whereas the remaining genera showed a higher abundance in the polyps group. Additionally, the comparison of healthy control and polyp groups showed six significantly abundant genera. More than 66% of these genera showed a reduced abundance in the polyps group than in healthy controls, whereas the remaining genera were highly abundant in the polyps group. Based on tumor presence and absence, the abundance of Olsenella and Lactobacillus at the genus level was significantly reduced in the patient group compared to healthy controls. The significant microbial function prediction revealed an increase in the abundance of metabolites in the polyps and cancer groups compared to healthy controls. A correlation analysis revealed a higher contribution of Dorea in the predicted functions. This study showed dysbiosis of gut microbiota at the taxonomic level and their metabolic functions among healthy subjects and in two stages of colorectal cancer, including adenoma and adenocarcinoma, which might serve as potential biomarkers for the early diagnosis and treatment of CRC.