Grade Of Colorectal Cancer Research Articles

T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma.

The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

Association of BMP4 RS444235 Gene Polymorphism and the Stage and Grade of Colorectal Cancer at Prof. dr. I G.N.G Ngoerah General Hospital

Association of BMP4 RS444235 Gene Polymorphism and the Stage and Grade of Colorectal Cancer at Prof. dr. I G.N.G Ngoerah General Hospital

Association Between BsmI Vitamin D Receptor Gene Polymorphism and Clinicopathological Features of Colorectal Cancer Patients in 2019-2020 at Prof. Dr. I.G.N.G Ngoerah Denpasar Bali

Aging is related to the occurrence of cancer. Colorectal cancer is one of the most common types of cancer found in Indonesia. The BsmI vitamin D receptor polymorphism has been extensively studied before and has been associated with colorectal cancer. This study aims to determine the relationship between the BsmI vitamin D receptor polymorphism and the clinicopathological features of colorectal cancer patients in 2019-2020 at Prof. dr. I.G.N.G Ngoerah Denpasar Bali. This research is a cross-sectional analytical research. The study was conducted at the Biomedical Laboratory Unit of the Faculty of Medicine, Udayana University from June to December 2022. A total of 35 samples were obtained from stored biological materials of colorectal cancer patients who were treated at the Digestive Surgery Polyclinic at Prof. RSUP. dr. I.G.N.G Ngoerah in 2019-2020 in the Udayana University Biochemistry laboratory. To detect the status of the BsmI polymorphism, DNA segments were amplified by the polymerase chain reaction (PCR) method and followed by sequencing. The results showed from 35 samples, 8 samples (22.9%) had the GG allele and 27 samples (77.1%) had the GA allele. A statistically significant association was found between BsmI vitamin D receptor polymorphisms and colorectal cancer grading (p=0.016), but no significant association was found between BsmI vitamin D receptor polymorphisms and the histopathological type of colorectal cancer (p=0.553). The conclusion of this study is that there is a significant relationship between BsmI vitamin D receptor polymorphism and grading, but not with the histopathological type of colorectal cancer, age and gender of colorectal cancer patients in 2019-2020 at Prof. dr. I.G.N.G Ngoerah Denpasar Bali. Keywords: Colorectal cancer, Vitamin D receptor, BsmI polymorphism, clinicopathology.

Association of CCND1 Gene Polymorphism rs9344 with Grade and Invasion Degree of Colorectal Cancer at Prof. Dr. I.G.N.G. Ngoerah Central General Hospital

The majority of colorectal cancer (CRC) are sporadic CRC that can be caused by genetic variations such as Single Nucleotide Polymorphisms (SNPs). The CCND1 gene polymorphism rs9344 could involve at the beginning and the development of CRC. This study aimed to analyze the association between CCND1 gene polymorphism rs9344 with the grade and invasion degree of colorectal cancer in at Prof. Dr. I.G.N.G. Ngoerah Central General Hospital, Denpasar, Bali. This cross-sectional study was carried out at the Integrated Biomedical Laboratory Unit, Faculty of Medicine, Udayana University. Data analysis of 32 samples showed majority age was above 50 years old as many as 28 (87.5%), with men as 21 samples (65.6%). Histopathology description was adenocarcinoma in 32 samples (100%). Grading histopathology low grade was 31 samples (96.6%). The degree of tumor invasion was high as 25 samples (78.1%). From the aspect of pathological stage pNx as much as 27 (84.4%). The majority location of tumors was on the left side as 21 samples (65.6%). The polymorphisms of CCND1 rs9344 genotype sequentially AA as 20 samples (62.5%), AG as 9 samples (28.1%), while GG as 3 samples (9.4%). The statistical analysis found that CCND1 gene polymorphism rs9344 was not associated with colorectal cancer grade (p&gt;0.05), and not associated with invasion degrees of colorectal cancer (p&gt;0.05). Taken together, we conclude that no significant association between the CCND1 gene polymorphism rs9344 with grade and invasion degree of colorectal cancer at Prof. Dr. I.G.N.G. Ngoerah Central General Hospital, Denpasar, Bali.

The Association Between CYP24A1 rs4809957 Gene Polymorphism and Grade of Colorectal Cancer at Prof. Dr. I G.N.G Ngoerah Hospital in Bali

Introduction: Colorectal cancer (CRC) is a malignancy in the large intestine, including the colon and rectum. One of the pathogenesis of CRC is the molecular pathway. This study aimed to evaluate the association between the CYP24A1 rs4809957 gene polymorphism and the histopathological grade of CRC patients at Prof. Dr. I G.N.G. Ngoerah Hospital in 2018-2019. Methods: This research was an observational analytic study with a cross-sectional design. This study used 34 samples of stored biological material from CRC tissue. CYP24A1 polymorphism (rs4809957) was identified using qPCR. Results: The results showed that the mean ± SD of the patient’s age was 61.09 ± 11.79 years. A total of 18 patients (52.9%) of the patient sample were male, and 16 patients (47.1%) were female. The histopathological grade of CRC in this study consisted of 30 samples (88.2%) of low grade and 4 (11.8%) of high grade. There were 21 patients (61.8%) who had a history of smoking. In addition, 20 patients (58.8%) had a history of consuming alcoholic beverages. This study’s CYP24A1 rs4809957 gene polymorphism comprised the AA+AG genotype in 23 samples (67.6%) and GG in 11 (32.4%). There was no significant association between the CYP24A1 rs4809957 gene polymorphism and the histopathological grade of CRC with a p-value = 0.580 and PR (95%CI) = 2.33 (0.83 – 19.42). Conclusion: This study concluded that there was no significant association between the CYP24A1 rs4809957 gene polymorphism and the histopathological grade of CRC patients.

Polysaccharide immunization and colorectal cancer: A systematic review and network meta-analysis.

Polysaccharides have a variety of biological activities, and in the anti-tumor field, they produce tumor suppressive effects by regulating the polarization of tumor-associated macrophages (TAMs). In immunotherapy, it has significant activities in modulating cytokines and antibody production. We reviewed them and selected CD24, an immune target, for meta-analysis with colorectal cancer (CRC) to investigate the correlation between CD24 expression and CRC. Correlation of CD24 positive expression with clinical-pathological features: age, sex, Duke’s stage, diameter, depth of invasion, degree of differentiation, and lymph node metastasis. It showed that: CD24 expression in CRC was significantly correlated with advanced nuclear grade of CRC, lymph node metastasis, Duke’s stage of CRC and age of CRC patients, while there was no significant correlation with gender, tumor diameter and invasion depth. The aim is to clarify the specific mechanism of polysaccharide immune anti-tumor, combined with targeted site-specific anti-solid tumor.

Unusually high incidence of polyomavirus JC infection in the higher grade of colorectal cancer tissues in Taiwan

IntroductionThe human JC polyomavirus (JCPyV) has been detected in colorectal cancer (CRC) tissues and is suggested to contribute to CRC tumorigenesis. The rearrangement of the JCPyV regulatory region is supposedly associated with CRC development. The progression of CRC involves the stepwise accumulation of mutations. The large tumor antigen (LT) of JCPyV can trigger uncontrolled cell cycle progression by targeting oncogenes, and tumor suppressor genes, and causing chromosome instability. Few studies have focused on the presence of JCPyV DNA in the higher grade of CRC tissues.MethodsWe collected 95 tissue blocks from samples of stages I, II, III, and IV CRC. Nested PCR targeting the regulatory region of the viral genome was performed to determine the presence of JCPyV DNA in the various stages of colorectal cancer tissues.ResultsThe nested PCR results showed that the positive rate of JCPyV DNA increased with the progression of CRC stages. The archetypal-like, non-rearrangement genotype of JCPyV with subtle mutations was the major genotype found in CRC samples.ConclusionsThis finding in our study suggests that there may be an association between JCPyV and CRC progression.

Divide-and-Attention Network for HE-Stained Pathological Image Classification.

Simple SummaryWe propose a Divide-and-Attention network that can learn representative pathological image features with respect to different tissue structures and adaptively focus on the most important ones. In addition, we introduce deep canonical correlation analysis constraints in the feature fusion process of different branches, so as to maximize the correlation of different branches and ensure that the fused branches emphasize specific tissue structures. Extensive experiments on three different pathological image datasets show that the proposed method achieved competitive results.Since pathological images have some distinct characteristics that are different from natural images, the direct application of a general convolutional neural network cannot achieve good classification performance, especially for fine-grained classification problems (such as pathological image grading). Inspired by the clinical experience that decomposing a pathological image into different components is beneficial for diagnosis, in this paper, we propose a Divide-and-Attention Network (DANet) for Hematoxylin-and-Eosin (HE)-stained pathological image classification. The DANet utilizes a deep-learning method to decompose a pathological image into nuclei and non-nuclei parts. With such decomposed pathological images, the DANet first performs feature learning independently in each branch, and then focuses on the most important feature representation through the branch selection attention module. In this way, the DANet can learn representative features with respect to different tissue structures and adaptively focus on the most important ones, thereby improving classification performance. In addition, we introduce deep canonical correlation analysis (DCCA) constraints in the feature fusion process of different branches. The DCCA constraints play the role of branch fusion attention, so as to maximize the correlation of different branches and ensure that the fused branches emphasize specific tissue structures. The experimental results of three datasets demonstrate the superiority of the DANet, with an average classification accuracy of 92.5% on breast cancer classification, 95.33% on colorectal cancer grading, and 91.6% on breast cancer grading tasks.

An Association BetweenBlastocystisSubtypes and Colorectal Cancer Patients: A Significant Different Profile from Non-cancer Individuals.

PurposeBlastocystis is a common enteric human parasite of non-conclusive pathogenicity which may be determined by subtype (ST) variation. Colorectal cancer (CRC) is considered one of the primary causes of cancer mortality. Blastocystis ST7 has been shown to reduce beneficial intestinal microbiota and may exacerbate CRC. This study assessed the possible association between Blastocystis STs and CRC in comparison to non-cancer patients.Material and MethodsA total of 200 fecal samples were obtained from CRC (100) and non-CRC (100) individuals attending Beni-Suef University Hospital, Egypt. Blastocystis was searched for in all samples using microscopy and culturing. Positive subculture samples were genetically sequenced and subtyped using conventional polymerase chain reaction (PCR). Blastocystis STs were determined by sequencing and a phylogenetic tree was created. Related patient characteristics and tumor stages were analyzed for association with presence of Blastocystis.ResultsBlastocystis was identified in 52% and 42% of CRC and non-cancer individuals, respectively. ST1, 2, and 3 were isolated from both cancer and non-cancer individuals; however, for the first time, ST7 was only isolated from CRC stool samples with significant association. Associated patient characteristics were evaluated as predictors.ConclusionBlastocystosis is highly prevalent in CRC patients, predominantly in the latest CRC grades and stages. To the best of our knowledge, this is the first study to report the identification of Blastocystis ST7 in CRC patients. To determine whether certain STs of Blastocystis are associated with CRC would require further research, including the role played by gut microbiota.

Colorectal cancer and Blastocystis sp. infection

BackgroundBlastocystis sp. is a common intestinal protozoan found worldwide. Based on gene analysis, 17 subtypes (STs, ST1–ST17) have been identified, 9 of which have been isolated from humans. Differences in clinical consequences may depend on differences among the STs. Here, we evaluated the prevalence of Blastocystis sp. in patients with colorectal cancer (CRC) compared to a control group and assessed the relationships between Blastocystis sp. infection and sex; age; and CRC grade, stage, and location.MethodsThe study included 107 CRC patients (41 women and 66 men, median age 65 years); 124 subjects without colorectal cancer or a history of oncological disease comprised the control group (55 women and 69 men, median age 63). Stool samples were collected from patients before oncological treatment and examined using light microscopy (iodine-stained smear). Additionally, PCR-based identification of Blastocystis sp. was performed in 95 stool samples from CRC patients and 76 stool samples from the control group.ResultsLight microscopy showed that the prevalence of Blastocystis sp. was significantly higher in CRC patients than in the control group (12.15% and 2.42%, respectively; p = 0.0041). Multivariate analysis showed that the odds of Blastocystis sp. infection were fivefold higher in the CRC group than in the control group. PCR-based molecular examinations demonstrated that the proportion of patients infected with Blastocystis sp. was significantly higher in the CRC group than in the control group (12.63% and 2.63%, respectively; p = 0.023). The predominant ST in the CRC group was ST3, detected in nine patients (75%), followed by ST1 (2 patients, 16.7%) and ST2 (1 patient, 8.3%). No association was found between Blastocystis sp. infection and age, sex, or CRC stage, grade, or location.ConclusionsThe results showed that CRC was associated with an increased risk of opportunistic Blastocystis sp. infection, even before oncological treatment. To the best of our knowledge, this is the first report estimating the prevalence of Blastocystis sp. infection in CRC patients before oncological treatment in Europe.

The Proteomic Expression of Nuclear Apoptosis-Inducing Factor1 (NAIF1) in Colorectal Tissues

The neogenic recombinases are potentially a source of genetic variability possibly implicated in themechanisms of genetic instability involved in the processes of carcinogenesis. One of these neogenicrecombinases is the nuclear apoptosis-inducing factor 1(NAIF1), which codes the protein NAIF1 thatinduces apoptosis in various human cancers.The aim of this work is to study the expression of NAIF1 neogene in cancerous and non-cancerous colorectaltissues.The protein expression of NAIF1gene has been studied by western blot method in the samples of proteinextracted from 29 patients with colorectal cancer.The result of this study showed that the protein expression of NAIF1 was found in both cancerous andnon-cancerous colorectal tissues, but it is highly expressed in non-cancerous tissues adjacent to cancerousone. Its expression is higher in non-metastatic cancerous tissues compared with metastatic one. Also thisexpression is higher in microsatellite instable (MSI) group of cancer compared with microsatellite stable(MSS) group.It can be concluded that NAIF1 protein expression inversely related with more advanced stage or grade ofcolorectal cancer and it may have a role in inhibition of proliferation, migration and invasion of colorectalcancer by inducing apoptosis.

The potential value of miRNA-223 as a diagnostic biomarker for Egyptian colorectal patients.

Colorectal cancer (CRC) is the third lethal malignancy worldwide. Dysregulation of microRNAs (miRNAs) mediates several growth factors signaling pathways and induces abnormal genes expression, which leads to colorectal carcinogenesis. We aimed to comprehensively assess the expression of miRNA-200c, miRNA-203a, miRNA-223 in Egyptian CRC tissue and their corresponding serum samples and to explore if they have any potential prognostic or diagnostic value for CRC patients. A total of 195 subjects (120 CRC patients and 75 healthy controls) participated in exploration and validation sets. The relative expression of miRNA-200c, miRNA-203a, and miRNA-223 was measured in both CRC tissue and serum samples, and the expressed miRNAs were compared in different CRC grades and types and the prognostic value was evaluated. The expression levels of miRNA-200c and miRNA-203a were reduced in CRC tissue samples than adjacent noncancerous tissues. miRNA-223 level was significantly upregulated in both CRC tissue and serum samples with a positive association between them (r = 0.85, P = 0.001). The miRNA-223 can effectively discriminate CRC patients from controls and can significantly differentiate between colon and rectal cancer patients. The association between serum miRNA-223 expression and CRC development was validated in the second set and the ROC curve showed highly significant prognostic value with 90.1% sensitivity, 87% specificity, and area under the curve of 0.914 (95% confidence interval: 0.830-0.978, P = 0.0001). These results showed the association between miRNA-223 upregulation and the CRC carcinogenesis. Circulating miRNA-223 can be a potential noninvasive prognostic biomarker for Egyptian CRC patients.

A Study of Significance of Poorly Differentiated Clusters in Colorectal Carcinomas: Association with Histopathological Prognostic Factors

Introduction: Colorectal Cancer (CRC) is the third most common cancer worldwide with prevalence rate of 47 million per five years and 1.8 million new cases per year. Routinely differentiation-based histologic grading of CRC is used, but its clinical impact is limited by insufficient prognostic value, inter-observer variability and the difficulty of its application to specific CRC’s like mucinous, micropapillary, signet ring cell and medullary carcinomas. To overcome this, Poorly Differentiated Cluster (PDC) based grading have been proposed recently in 2012 by Ueno H et al., PDC is defined as a solid cancer cell nest comprising ≥5 cancer cells, lacking a gland-like structure. Aim: To compare PDC based grading with conventional World Health Organisation (WHO) grading in resected specimens of colorectal adenocarcinomas and to evaluate the relationship of PDC grading with known prognostic histopathological parameters. Materials and Methods: The present study was a descriptive study done duration of three years and two months in the Department of Pathology, JSS Medical College and Hospital, Mysuru, Karnataka, India. A total of 60 CRC cases were studied. WHO grading was done according to eighth edition, 2018 of the American Joint Committee on Cancer (AJCC) staging system. Haematoxylin and Eosin (H&amp;E) stained slides were studied by two pathologists and looked for inter-observer variability by k statistics. Finally, both pathologists arrived at a consensus and was subjected for PDC grading and correlated with other prognostic histological markers. The comparison of data was done by Pearson’s Chi-square test and t-test. The p-values &lt;0.05 were considered statistically significant. Fleiss-Cohen’s weighted k statistics was used for the assessment of inter-observer variability in tumour grading. Results: There was significant association between PDC grading and WHO grading with k-value of 0.852 and p-value of 0.001. The maximum cases on PDC grading were of G-II type-29 (48.3%) followed by G-III-25 (41.7%) and G-I-6 (10%). There was increase in G-II and G-III carcinomas, as mucinous adenocarcinoma and signet ring cell carcinomas were also graded with PDC which was not possible with current WHO grading system. Conclusion: Present study findings suggest that PDC grading is more reproducible and provides better prognostic stratification as it is less subjective than the conventional WHO grading.

Interrelations of Apoptotic and Cellular Senescence Genes Methylation in Inflammatory Bowel Disease Subtypes and Colorectal Carcinoma in Egyptians Patients.

Ras-related domain family member 1 transcript variant A (RASSF1A) controls apoptosis and cell proliferation while p14/ARF gene has a regulatory role in cellular senescence. Failure of apoptosis and cellular senescence occurs during inflammatory bowel disease (IBD) and colorectal cancer (CRC). To reveal the role of peripheral leukocyte promoter methylation of RASSF1A and p14/ARF in the pathogenesis of IBD subtypes and CRC we investigated the methylation state of the two genes by methylation-specific polymerase chain reaction (MSP-PCR) in 60 CRC patients, 60 patients with IBD; 27 with ulcerative colitis and 33 had Crohn's disease and also in 30 healthy subjects. Methylated RASSF1A and p14/ARF genes were detected in 55% and 60% of CRC, while the frequency of the methylated RASSF1A and p14/ARF genes was 23.3% and 43.3% in IBD patients and 3.3% and 13.3% in the control group (P = 0.000 each). Also, the frequency of methylated RASSF1A gene was significantly higher in ulcerative colitis than in Crohn's disease, while a non-significant frequency of methylated p14/ARF was detected between ulcerative colitis and Crohn's disease. Furthermore, methylated RASSF1A and p14/ARF were associated with the grade of CRC but not associated with the age of patients, family history, or tumor location. Results suggest that methylated RASSF1A and p14/ARF are related to CRC and IBD pathogenesis and may be used as molecular biomarkers for early detection of CRC and IBD.

Quantitative immunochemical fecal occult blood test for neoplasia in colon cancer screening.

To investigate the performance of the quantitative immunochemical fecal occult blood test (qFIT) and to determine the association between the fecal hemoglobin (Hb) level and the location and size of adenomas and the stages of colorectal cancer (CRC). A total of 692 participants were included in the study. Their fecal Hb level was measured using an OC-SENSA MICRO qFIT. The colonoscopy results, including the location, size, and histological features of the adenomas, as well as the relationship between the Hb level and different characteristics were analyzed. Performance of the qFIT at various thresholds of fecal Hb levels was evaluated. Advanced colorectal neoplasia (ACRN) was identified in 76 patients based on the colonoscopic and pathological examinations. Large adenomas (≥10 mm) had a higher fecal Hb level than small adenomas (<10 mm). Advanced adenomas located on the left side of the colon presented with a higher fecal Hb level than those on the right side (P = 0.022). Stage III-IV CRC patients had a significantly higher Hb level than stage I-II patients (P = 0.013). The sensitivity and specificity of qFIT for ACRN was 51.3% and 86.4%，respectively, with the best cut-off level of 400 ng/mL. The sensitivity and specificity for CRC was 61.0% and 89.1%, with the best cut-off level of 500 ng/mL. qFIT has an acceptable sensitivity and specificity for ACRN detection. Furthermore, the qFIT results are associated with the location and size of adenomas as well as the grade of CRC.

Pathologic and molecular characteristics of colorectal cancer in patients with type 2 diabetes

Objective Type 2 diabetes increases the risk of colorectal cancer and reduces the survival rate of the patients. Therefore, analyzing the characteristics of colorectal cancer in patients with type 2 diabetes may help to develop precise medical measures and to improve the prognosis of patients. Methods The pathological characteristics of 123 colorectal cancer cases with or without type 2 diabetes were analyzed. In addition, PCR and pyrosequencing method were used to test the common gene mutation status of colorectal cancer, including KRAS(codons 12, 13, 61, and 146), BRAF(codon 600), and PIK3CA (exons 9 and 20), in order to investigate the molecular characteristics of colorectal cancer in diabetic patients which may provide some clues to clinical decision. Results The mean age and body mass index of patients with diabetes were higher than those of patients without diabetes, but there was no difference in the location, the degree of cell differentiation and the grade of colorectal cancer between these 2 groups. The rate of PIK3CA mutation in patients with type 2 diabetes mellitus, especially in patients with long term type 2 diabetes was significantly higher than that in patients without diabetes (28.6% vs 10.3%, P<0.05). There was no significant difference between the two groups in common BRAF and KRAS mutation sites. Conclusion Diabetes does not alter the clinical pathological characteristics of colorectal cancer, but long course type 2 diabetes increases PIK3CA mutation rate. Therefore, using medicine targeting PIK3CA gene mutation may help to improve the prognosis of patients. (Chin J Endocrinol Metab, 2018, 34: 655-659) Key words: Colorectal cancer; Diabetes mellitus, type 2; Gene mutation

Abstract 5057: Exposure to highly energetic charged (hze) particle radiation is associated with higher colitis and colorectal cancer incidence in IL10-/- mice

Abstract Epidemiological data from atom-bomb survivors and from radiotherapy patients have highlight an underlying risk of colitis and colorectal cancer (CRC) after ionizing radiation-exposure. In contrast, astronauts planning to undertake deep space exploration such as mission to Mars have risk of radiation exposure from highly energetic charged (HZE) particles present in galactic cosmic radiation (GCR) and risk of colitis and CRC after HZE-exposure is yet to be determined. Therefore, animal studies are warranted to address existing uncertainties in colitis and CRC risk prediction after exposure to HZE radiation. Here we report IL10-/- mice as a suitable mouse model for assessment of colitis and CRC risk after exposure to space radiation. Male mice (n=12 mice/group) were whole-body exposed to sham-radiation, γ-rays and 28Si-ion (300 MeV/n; 70 keV/μm; 1.4 Gy). Mice were sacrificed three months after irradiation, and colon swiss-rolls sections were analyzed for colitis and CRC grade was noted in hematoxylin and eosin stained sections. Immunohistochemistry (β-catenin, Cyclin-D1, phospho-H3, iNOS, phoshoNfKβ-p65, and Cox2) was also performed to assess HZE-induced proliferative and inflammatory signaling. Further, inflammation-associated gene-expression analysis was also conducted in both radiation-induced tumor and adjoining normal tissue area. Here we report that relative to controls and γ-ray, colitis score, colon tumor incidence, size and grade was significantly higher after space (28Si-ion) radiation exposure. Higher number of phospho-H3 positive cells in 28Si-ion exposed mouse colon demonstrated increased proliferative index and in increased colon tumors of higher grade, could be due to greater activation of β-catenin and its downstream effector cyclin D1. In addition, higher accumulation of iNOS, phoshoNfKβ-p65, and Cox2 in stromal and epithelial cells after space radiation exposure clearly indicates upregulation of both immune and epithelial inflammation as drivers of colitis and CRC development. Inflammation associated protein markers and gene expression signatures were more pronounced after 28Si-ion exposure. Significant up-regulation of GATA4, ICAM1, ITGA2 and EGFR were exclusive to 28Si-ion exposed mouse colon, however PTGES and TGFβ1 were upregulated in both γ and 28Si-ion exposed mice. Overall, this study suggests that IL10-/- mouse are a suitable model to assess IR-induced colitis and CRC risk, and that space radiation carries higher risk of colitis and CRC incidence, relative to γ-rays at comparable doses. This study has implications for risk prediction in astronauts planning for deep space mission and also for cancer patients planning to undergo particle radiotherapy. Citation Format: Shubhankar Suman, Bo-Hyun Moon, Albert J. Fornace, Kamal Datta. Exposure to highly energetic charged (hze) particle radiation is associated with higher colitis and colorectal cancer incidence in IL10-/- mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5057.

Expressions of octamer-binding transcription factor 4 and phosphorylated-protein kinase B in colorectal cancer and their clinical significances

Objective To investigate the expressions of octamer-binding transcription factor 4 (Oct4) and phosphorylated-protein kinase B (p-Akt) proteins in colorectal cancer and their clinical significances, in order to explore the roles of Oct4 and p-Akt in the staging and grading of colorectal cancer. Methods Immunohistochemical technique was used to examine the expression of Oct4 and p-Akt proteins in 78 cases of colorectal cancer in Wuxi Second Hospital of Traditional Chinese Medicine and Wuxi First People's Hospital from January 2011 to December 2016. Relationship between expressions of Oct4 and p-Akt proteins and clinicopathological parameters were analyzed. Results The positive rate of Oct4 in tumors was 74.36 % (58/78), which was obviously higher than that in normal tissues [35.90 % (20/78), χ2 = 23.32, P < 0.01]; and the positive rate of p-Akt in tumors was 67.95 % (53/78), which was obviously higher than that in normal tissues[28.21 % (25/78), χ2 = 24.68, P < 0.01]. The double positive and negative expression rate of these two proteins accounted for 80.8 % (63/78), with a linear positive correlation (r = 0.455, P < 0.000 1). In 78 cases of colorectal cancer, the expression of Oct4 protein was correlated with histological grade, lymph node metastasis, and Duke staging (all P < 0.05), and the expression of p-Akt protein was correlated with histological grade and lymph node metastasis (both P < 0.05). The multivariate logistic regression analysis showed that the expression of Oct4 protein was related to histological grade and Duke staging (both P < 0.05), and the expression of p-Akt protein was only related to lymph node metastasis (P < 0.05). Conclusion The combined detection of Oct4 protein and p-Akt protein has reliable and important clinical significance for judging the histological grade, lymph node metastasis and Duke staging of colorectal cancer. Key words: Colorectal neoplasms; Octamer-binding transcription factor 4; Phosphorylated-protein kinase B

Radiomics Evaluation of Histological Heterogeneity Using Multiscale Textures Derived From 3D Wavelet Transformation of Multispectral Images.

Colorectal cancer (CRC) is markedly heterogeneous and develops progressively toward malignancy through several stages which include stroma (ST), benign hyperplasia (BH), intraepithelial neoplasia (IN) or precursor cancerous lesion, and carcinoma (CA). Identification of the malignancy stage of CRC pathology tissues (PT) allows the most appropriate therapeutic intervention. This study investigates multiscale texture features extracted from CRC pathology sections using 3D wavelet transform (3D-WT) filter. Multiscale features were extracted from digital whole slide images of 39 patients that were segmented in a pre-processing step using an active contour model. The capacity for multiscale texture to compare and classify between PTs was investigated using ANOVA significance test and random forest classifier models, respectively. 12 significant features derived from the multiscale texture (i.e., variance, entropy, and energy) were found to discriminate between CRC grades at a significance value of p < 0.01 after correction. Combining multiscale texture features lead to a better predictive capacity compared to prediction models based on individual scale features with an average (±SD) classification accuracy of 93.33 (±3.52)%, sensitivity of 88.33 (± 4.12)%, and specificity of 96.89 (± 3.88)%. Entropy was found to be the best classifier feature across all the PT grades with an average of the area under the curve (AUC) value of 91.17, 94.21, 97.70, 100% for ST, BH, IN, and CA, respectively. Our results suggest that multiscale texture features based on 3D-WT are sensitive enough to discriminate between CRC grades with the entropy feature, the best predictor of pathology grade.

Circulating Exosomal miR-17-5p and miR-92a-3p Predict Pathologic Stage and Grade of Colorectal Cancer

Exosomes are extracellular membrane vesicles of 50- to 130-nm diameter secreted by most tumor cells. Exosomes can mediate the intercellular transfer of proteins and RNAs, including microRNAs (miRNAs), and promote both tumorigenesis and premetastatic niche formation. In this study, we performed exosomal RNA sequencing to identify candidate exosomal miRNAs that could be associated with colorectal cancer (CRC) and its distant metastasis. The expression profiles of exosomal miRNA, as secreted by isogenic human primary CRC cell line SW480 and highly metastatic cell line SW620, were analyzed and the potential targets related to tumorigenesis and metastatic progression were investigated. We found that 25 miRNAs had been up-regulated and 5 miRNAs had been down-regulated in exosomes purified from SW620 culture supernatant. Candidate miRNAs were further evaluated for CRC diagnosis using quantitative real-time polymerase chain reaction in CRC patients. Higher expression levels of circulating exosomal miR-17-5p and miR-92a-3p were significantly associated with pathologic stages and grades of the CRC patients. CONCLUSIONS: Circulating exosomal miR-17-5p and miR-92a-3p may provide a promising noninvasive prognostic biomarker for primary and metastatic CRC.