Frequency Of Colorectal Cancer Research Articles

Analysis of patch-based GCN risk score distribution corresponding to gene mutations in colorectal cancer using whole slide images.

e15650 Background: Colorectal cancer (CRC) is one of the most common malignancies, with the third highest incidence and the second highest mortality in the world. Risk scores are typically employed to predict outcomes such as disease risk, prognosis, or treatment response. Risk scores are usually calculated by combining biomarkers or genetic variants with statistical models, such as logistic regression or Cox proportional hazards models, and then observe the relationship between genetic variations and survival time through survival analysis. We have constructed a deep learning model based on Graph Convolutional Networks (GCNs), which is capable of predicting risk scores using Whole Slide Images (WSIs). Statistical analyses were applied to explore the distribution of risk scores associated with different variants in colorectal cancer. Methods: We performed risk scores prediction on a total of 384 samples from TCGA-COAD and TCGA-READ using our patch-based GCN model. We analyzed the distribution of risk scores in colorectal cancer samples and investigated the effects of gene mutations in key pathways on these risk scores. Results: Risk score predictions by our patch-based GCN model were conducted on 384 samples, revealing that the maximum, minimum, median, mean, and standard deviation of risk scores were -0.78, -1.89, -1.34, -1.34, and 0.20, respectively. The data overall conformed to a normal distribution ( p < 0.05 ). We selected core genes in key pathways combined with top ten genes with the highest mutation frequency in colorectal cancer for statistical analysis to explore the correlation with the predicted risk scores. These gene mutations were found in a total of 346 patients. The results indicated that mutations in the TP53 and OBSCN genes led to significant differences in risk scores as predicted by our model ( p < 0.05 ). The risk scores based on gene mutations also have significant differences and consistent trend in these genes. Conclusions: Our results indicate the risk scores generated by the patch-based GCN model have the consistent trend with the risk scores generated by mutation information of core genes in colorectal cancer. Whether risk scores based on digital pathology prediction can replace mutation detection in predicting patient survival status requires further exploration.

Evaluation of Colorectal Cancer Screening Awareness and Compliance Rates over the Age of 40: Single Center Data in Türkiye

The frequency of colorectal cancer is increasing under the age of 50, and new sights have emerged regarding the initiation of screening in the earlier age group. This study aims to measure the consciousness of patients over the age of 40 about colorectal cancer screening and to reveal the screening rates of individuals over the age of 50. 300 consecutive patients who applied to our center and were older than 40 years of age were included. The questionnaire was created based on current guidelines and literature knowledge by the investigators and done through face-to-face interviews. Patients over 50 years of age who did not undergo screening were analyzed by dividing them into groups according to their socio-demographic characteristics and colorectal cancer risk factors. While 64.7% of the participants stated that they knew about colorectal cancer screening, only 32.4% of the participants aged 50 and over had colorectal cancer screening. The vast majority of patients stated that they did not have enough knowledge about the subject. The rate of participants who stated that they were considering entering the cancer screening program after completing this questionnaire was 73.7%. Colorectal cancer screening rates of non-smokers, women, and married participants were higher than the other group (P=0.016, P=0.017, and P=0.033, respectively). This study shows low screening compliance of individuals over the age of 50. We think that it is important to encourage and inform all adults over the age of 40 about colorectal cancer screening for public health.

Risks and Histoprognostic Factors of Colorectal Cancer in East of Algeria

The frequency of colorectal cancer (CRC) is gradually increasing in the Algerian population. It ranks 3rd among the most common cancers. Diet and lifestyle are the factors that play a role in developing these cancers. CRC is a major public health problem; it is essential to determine the factors causing this disease. In our retrospective study conducted at the Cancer Center from January to December 2019, which involved 60 cases with CRC, it was noted that the most representative age group is between 51 and 60 years old (46.7%). There is a predominance of the female sex with 60% of the cases against 40% of the male sex. Obesity Type 2 represents the highest rate of cases with 45% and overweight with 43.3%. We note that 75% of patients have no surgical history and 25% are operated. The left colon and the transverse colon are the most affected (53.85% and 30.77%). It is noted that the class with the highest rate is grade T3N2Mx with 46% of cases. Our results show that obesity, as well as diabetes and hypertension and family history of digestive cancers are closely related to colorectal risk.

Delayed Colorectal Cancer Diagnosis during the COVID-19 Pandemic in Alberta: A Framework for Analyzing Barriers to Diagnosis and Generating Evidence to Support Health System Changes Aimed at Reducing Time to Diagnosis.

The frequency of colorectal cancer (CRC) diagnosis has decreased due to the COVID-19 pandemic. Health system planning is needed to address the backlog of undiagnosed patients. We developed a framework for analyzing barriers to diagnosis and estimating patient volumes under different system relaunch scenarios. This retrospective study included CRC cases from the Alberta Cancer Registry for the pre-pandemic (1 January 2016–4 March 2020) and intra-pandemic (5 March 2020–1 July 2020) periods. The data on all the diagnostic milestones in the year prior to a CRC diagnosis were obtained from administrative health data. The CRC diagnostic pathways were identified, and diagnostic intervals were measured. CRC diagnoses made during hospitalization were used as a proxy for severe disease at presentation. A modified Poisson regression analysis was used to estimate the adjusted relative risk (adjRR) and a 95% confidence interval (CI) for the effect of the pandemic on the risk of hospital-based diagnoses. During the study period, 8254 Albertans were diagnosed with CRC. During the pandemic, diagnosis through asymptomatic screening decreased by 6·5%. The adjRR for hospital-based diagnoses intra-COVID-19 vs. pre-COVID-19 was 1.24 (95% CI: 1.03, 1.49). Colonoscopies were identified as the main bottleneck for CRC diagnoses. To clear the backlog before progression is expected, high-risk subgroups should be targeted to double the colonoscopy yield for CRC diagnosis, along with the need for a 140% increase in monthly colonoscopy volumes for a period of 3 months. Given the substantial health system changes required, it is unlikely that a surge in CRC cases will be diagnosed over the coming months. Administrators in Alberta are using these findings to reduce wait times for CRC diagnoses and monitor progression.

EMAST frequency in colorectal cancer: a meta-analysis and literature review.

Aim: The prognostic and predictive value of Elevated Microsatellite Alterations at Selected Tetranucleotide (EMAST) has been reported in colorectal cancer (CRC). The prevalence of EMAST in CRC varied across the literature. We conducted a meta-analysis to determine the prevalence of EMAST in CRC. Materials & methods: Three international databases including PubMed, ISI and Scopus were searched to identify related articles that described the frequency of EMAST. Results: Analysis was performed on 16 eligible studies including 4922 patients. The overall EMAST prevalence among CRCs patients was 33% (95% CI: 23-43%, I2=98%). Conclusion: This study indicated that approximately a third of the CRC patients are diagnosed with EMAST, hereupon EMAST as a prognostic and predictive biomarker should be more studied clinically.

Oxidative Stress Level in Onco-Surgical Treatment Dynamics at Patients with Malignant Colo-Rectal Tumors

Colorectal cancer (CRC) is one of the most common human malignancies, affecting one of 20 persons in areas with high socio-economic standard. In Romania, the frequency of colorectal cancer is growing rapidly placing the country among countries with an average incidence of the disease. There are some etiologic factors involved and treatment of disease is carried out after proper staging. Biochemical mechanisms underlying malignant transformation in colorectal cancer are not all fully understood, therefore our work trying to enter in the path of oxygen metabolism at patients surgically treated. The aim of the study is to follow the production of active metabolites of oxygen, in the dynamics of the surgical procedure, and how the endogenous natural protection systems are activated, following the invasive procedure. Oxidative stress biochemistry assays, realized before and after surgical excision showed a direct relationship between the production of reactive oxygen species and the presence of tumor, without being able to distinguish exactly if malignant tissue is able to induce oxidative stress, or the latter occurs due to neoplastic changes. Based on the results we can say with certainty that the reactive oxygen species ROS primary attack occurs in the lipids, and then the proteins, following activation of endogenous antioxidant defence.

Spontaneous regression of advanced transverse colon cancer with remaining lymph node metastasis

BackgroundThe observation of spontaneous regression (SR) has been well documented for many cancer types, including renal cell carcinoma, non-Hodgkin’s lymphoma, leukemia, neuroblastoma, and malignant melanoma. However, the SR frequency in colorectal cancer is very rare. Therefore, the accumulation of SR colorectal cancer cases might contribute to find the regression mechanism.Case presentationA 67-year-old woman received colonoscopy due to being positive for fecal occult blood testing and was diagnosed as having a transverse colon cancer at a local hospital. She was admitted to our institution for surgical treatment of the colon cancer. The colonoscopy revealed a type 2 tumor of 13 mm in diameter at the hepatic flexure of the transverse colon. The enhanced computed tomography (CT) showed an enlarged lymph node in the intermediate lymph node region. The 18F-fluorodeoxyglucose positron emission tomography/CT showed no abnormal accumulation on the transverse colon; however, an abnormal accumulation was found at the enlarged lymph node. The patient was preoperatively diagnosed as having advanced transverse colon cancer with lymph node metastasis and underwent laparoscopic right hemicolectomy with D3 lymph node dissection. Pathological examination showed only a scar-like tissue and no cancerous lesion in the transverse colon, while a metastatic lymph node was histologically confirmed in the intermediate lymph node region. Loss of MLH1 and PMS2 expression was observed in the cancer cells of both biopsy specimens and resected lymph nodes. No recurrence was seen for 5 years after surgery.ConclusionsWe reported a rare case of SR of the primary transverse colon cancer without regression of the metastatic regional lymph node. We considered that colorectal cancer with SR should be resected because even if SR of the primary lesion occurs, lymph node metastasis might have an inconsistent behavior as shown in the present case.

Cancer screening in adults with down syndrome, a proposal.

The specific distribution of cancers in Down syndrome (DS) calls into question the validity of screening policies for cancer surveillance as implemented for the general population. We performed a literature review of cancer screening opportunities for adults with DS, taking account of the tumor profile in this specific population. In DS, solid tumors in adults are at most half as common as in the overall group of persons with intellectual disabilities, who have a frequency similar to that of the general population. In women with DS, breast cancer is rare, the frequency of colorectal cancer is poorly described, and cervical cancer is rarely reported, although sometimes observed at an advanced stage. Young men have an increased risk of testicular cancer. We propose that adults with DS should participate in colon cancer screening. For women with DS, breast cancer screening is not recommended, but annual clinical monitoring should be conducted, with the option to perform ultrasound or MRI examination in suspect cases. For cervical cancer, screening could be proposed to women who are sexually active beginning at age 25 years. Annual surveillance for testicular cancer via palpation by a health professional is preferable from ages 15 to 45. In case of additional genetic predisposition in a person with DS, a surveillance similar to other family members is recommended. The specific tumor profile in DS warrants an adapted screening program for breast, colon, cervical and testicular neoplasia.

Frequency of Defective Mismatch Repair System in a Series of Consecutive Cases of Colorectal Cancer in a National Cancer Center.

The frequency of colorectal cancer (CRC) with defective mismatch repair (dMMR) is estimated between 5 and 15%. In our population, the frequency of dMMR is unknown. Our objective was to show the frequency of dMMR. Determination of dMMR with immunohistochemistry was performed prospectively for 202 patients who presented consecutively with CRC for the first time at our institution. The median age was 59years (IQR 47 to 68), 119 (58.9%) were women, and 43 (21.3%) cases showed dMMR. The only clinicopathological characteristics associated with dMMR were the location in the right colon and the presence of a family history of cancer. In the multivariate analysis, only the presence of the tumor in the right colon was associated with dMMR (OR = 5.823, 95%-C.I. = 2.653-12.784, p < .001). The 21.3% of the cases demonstrated a dMMR and the only clinical-pathological characteristic associated with dMMR was location in the right colon.

Prognostic Impact of Macroscopic Complete Resection and Inflammatory Status for Colorectal Cancer With Peritoneal Dissemination

Objective: To clarify the appropriate treatment policy for colorectal cancer with peritoneal metastasis, case series were analyzed retrospectively. Summary of background data: The frequency of colorectal cancer and peritoneal dissemination occurring simultaneously is 4% to 7%. The prevention of peritoneal metastasis and the development of a strategy for cure are considered important factors in improving the treatment outcome of colorectal cancer. Methods: A total of 60 patients with colorectal cancer with peritoneal dissemination were enrolled in this study. Tumor and host condition characteristics and treatment regimens affecting patient survival were tested by using Kaplan-Meier survival analysis. Results: Histologic type, carbohydrate antigen 19-9, macroscopic complete resection, and Glasgow Prognostic Score were found to be independent prognostic factors for overall survival. Conclusions: Peritoneal carcinomatosis can result in better patient prognoses in patients with well-differentiated carcinoma, less peritoneal spread, low levels of tumor markers, and a low Glasgow Prognostic Score. In these patients, curative resection of peritoneal metastases followed by intensive chemotherapy might be effective.

Early Interval Colorectal Cancer in the Inflammatory Bowel Disease Population: Is There a Role for Risk Stratification?

Introduction: Current guidelines recommend starting colorectal cancer (CRC) surveillance in patients with inflammatory bowel disease (IBD) 8-10 years after symptom-onset. Recent European studies report that the incidence of CRC preceding the 8-10-year recommendation ranges from 12-42%. We aimed to describe the frequency of early interval CRC in a United States IBD cohort and to identify risk factors for early interval CRC. Methods: We performed a case-control study of IBD patients diagnosed with CRC from 2005-2016. We compared characteristics of patients with early interval CRC (diagnosis of CRC within 8 years of IBD symptom-onset) to those with standard interval CRC. Statistical analysis was performed using chisquared and Fisher's exact test for categorical variables and Student's t-test or Wilcoxon Rank Sum test for continuous variables as appropriate. A multivariable logistic regression was performed controlling for all variables with a P-value <0.15. Results: 96 patients with IBD and CRC were identified. 12 (12.5%) patients developed CRC within 8 years of IBD symptom-onset (Figure 1). Patients with an early-interval CRC were older at IBD symptom-onset (mean 44.8 vs. 30.5 years; P=0.002) and slightly younger at the time of CRC diagnosis (mean 47.2 v. 55.2 years; P=0.078) than those with standard interval CRC. Active smoking was also associated with early interval CRC (27.3% v. 5.1%) (P=0.036). Patients with a history of systemic corticosteroid use (8.3% v 40.5%; P=0.051) and oral 5-aminosalicylic acid use (25.0% v. 60.7%; P=0.020) were less likely to have an early interval CRC. On multivariate logistic regression, when controlling for age at CRC diagnosis, age at IBD symptom-onset, gender, 5-aminosalicylic acid use, and smoking, both younger age at CRC diagnosis (odds ratio [OR] 0.57; 95% CI 0.35 - 0.91) and older age at IBD symptom-onset (OR 1.79; 95% CI 1.10-2.92) remain significant predictors of early interval CRC (Table 1).Figure: Frequency of Colorectal Cancer By Duration of Inflammatory Bowel Disease Symptoms.Table: Table. Predictors of Early Interval Colorectal Cancer Among Patients with Inflammatory Bowel DiseaseConclusion: A substantial number of patients with IBD develop CRC prior to the currently recommended timeframe for initiation of CRC surveillance. Risk stratifying patients based on predictors would allow us to individualize CRC surveillance for patients with IBD. Future studies should focus on developing a clinical tool that can be used to individualize the timing of CRC surveillance for this at-risk population. A multicenter study would allow us to better generalize our results as well as validate our predictors.

Circulating tumor DNA analysis before and after resection for colorectal cancer.

3597 Background: Detection of circulating tumor DNA (ctDNA) has broad clinical utility including disease monitoring, prognostication and response to chemotherapy. ctDNA is commonly detected by targeting tumor-specific features including mutations, insertions, deletions or hypermethylation. The two genes, BCAT1 and IKZF1, are methylated with high frequency in colorectal cancer (CRC). This study aimed to analyze the impact of tumor resection on ctDNA levels by assaying pre- and postoperative blood samples for methylated BCAT1 and IKZF1. Methods: 91 people (age 32-86 years, 53% male) with invasive CRC, but without neoadjuvant therapy, had blood collected prior to surgery and within 12 months (1-12 months) after resection. Cancers were clinicopathologically staged. DNA extracted from plasma was assayed for methylated BCAT1/ IKZF1 and detection of either marker was deemed positive for ctDNA. Results: 47 (52%) of the 91 CRC patients were ctDNA positive before resection, including 5/30 (17%) stage I, 17/28 (61%) stage II, 23/31 (74%) stage III and 2/2 (100%) stage IV. After resection 75% (35/47) became ctDNA negative (median 2 months after resection), and all had apparent tumour clearance. Of the 35 postoperative ctDNA negative cases 22 had further surveillance CT scans within study timeframe. 86% (20/22) showed no recurrent CRC but 2 of these developed a new cancer (metachronous CRC, prostate). The remaining 2 tested ctDNA positive 14 and 25 months later and recurrence was confirmed. Of the 12 postoperative ctDNA positive cases, two were found to not have complete tumour clearance at surgery (residual disease). Follow-up CT scans were available for a further 8 patients which revealed that 4 later presented with cancer (3 recurrence, 1 thyroid) at a median 15 months after resection. The remaining 4 postoperative positive cases were negative at subsequent blood testing (median 8 months later). Conclusions: Methylated BCAT1/IKZF1 DNA in preoperative blood is dependent on tumor stage, but informs the completeness of resection given the high rate (74.5%) of ctDNA disappearance post-surgery. If cases persistently test ctDNA positive after surgery or become ctDNA positive later, residual or recurrent disease should be suspected, respectively.

Measuring the effects of radiotherapy on DNA methylation in colorectal cancer.

e15089 Background: BCAT1 and IKZF1are methylated with high frequency in colorectal cancer (CRC). This study aimed to investigate the level of methylation in these two genes in tissue samples from CRC patients who had undergone radiotherapy. Methods: Tumor and adjacent non-tumor tissue was collected from 50 CRC patients, including 14 subjected to radiotherapy prior to surgical resection. DNA was extracted, bisulfite converted and the levels of methylated BCAT1 and IKZF1 DNA were expressed as the percentage of 5ng tissue DNA (normalized to ACTB levels). Results: In the 36 CRC patients who did not receive radiotherapy prior to resection, tumor tissues had high levels of methylated BCAT1 and IKZF1 compared with adjacent non-tumor tissues (p &lt; 0.001, Table). The CRC tissues from the 14 patients who received radiotherapy pre-surgery had significantly lower levels of methylation compared to the levels in tumors from non-treated patients (p&lt;0.01, Table). Radiotherapy did not appear to affect the methylated BCAT1/IKZF1DNA levels in adjacent non-cancer tissues (p &gt; 0.05, Table). In this limited dataset, a correlation was observed with %methylation and response to radiotherapy measured based on tumor size relative to original size, with the lowest methylation in the tumors associated with the greatest downsizing. Conclusions: The high levels of methylated BCAT1 and IKZF1 in CRC tissue and the low levels in the surrounding non-cancer tissue suggest that the markers are tumor specific with no obvious field effect. In contrast, in the samples obtained from patients treated with radiotherapy prior to resection, the methylation levels in CRC tissues were similar to the levels measured in the adjacent non-tumor tissues. Further studies are necessary to determine the reason for this and whether it has implications for monitoring response to therapy based on blood levels of methylated BCAT1 and IKZF1. [Table: see text]

Frequency of Her2/neu expression in colorectal adenocarcinoma: a study from developing South Asian Country.

BackgroundHuman Epidermal Growth Factor (Her-2/neu) has strong therapeutic implications in certain cancers like breast and gastric cancer. Literature on its frequency in colorectal cancer is scarce. In this study, we have investigated the frequency of Her-2/neu expression in colorectal adenocarcinomas and its association with various clinicopathological variables.MethodsA total of 95 patients who underwent colonoscopic biopsy or colectomy were studied after Institutional Ethical Approval. Hematoxylin & eosin (H&E) staining was performed on all the tissue sections. Expression of Her-2/neu was investigated by immunohistochemistry using α-Her-2 antibody. In order to quantify Her-2/neu expression, three criterias were applied that includes the pattern of staining, intensity of staining and percentage of tumor cells stained. Furthermore, its association was seen with various clinicopathological variables including age, gender, histopathological type, grade and stage of the tumor. Data was entered and analyzed using SPSS version 21. A p-value of < 0.05 was considered as significant.ResultsFrom the total of 95 cases, 75 (78.9 %) cases showed Her-2/neu expression. Pattern of Her-2/neu staining was significantly associated with the grade of colorectal cancer depicting cytoplasmic Her-2/neu expression higher in low grade (50 %) while membranous Her-2/neu expression more in high grade colorectal cancer (45 %) (P-value = 0.030). Pattern of Her-2/neu staining was also significantly associated with the type of colorectal cancer representing membranous Her-2/neu expression to be more common in mucinous type (38.5 %) while cytoplasmic Her-2/neu expression to be more frequent in non mucinous type (42.7 %) of colorectal cancer (p-value = 0.024).We observed a significant association between percentage of cells stained & tumor type, with score 3+ maximum in non mucinous type of colorectal cancer (p-value = 0.006).ConclusionHer2/neu is considerably expressed in colorectal adenocarcinoma in Pakistani population. Our findings indicate a significant strong association of cytoplasmic Her-2/neu expression with low grades and membranous Her-2/neu expression with high grades of colorectal cancer. These findings add to the body of information & may help in conducting clinical trials in future to explore its therapeutic significance as well.

Regulation of functional KCNQ1OT1 lncRNA by β-catenin.

Long noncoding RNAs (lncRNAs) have been implicated in many biological processes through epigenetic mechanisms. We previously reported that KCNQ1OT1, an imprinted antisense lncRNA in the human KCNQ1 locus on chromosome 11p15.5, is involved in cis-limited silencing within an imprinted KCNQ1 cluster. Furthermore, aberration of KCNQ1OT1 transcription was observed with a high frequency in colorectal cancers. However, the molecular mechanism of the transcriptional regulation and the functional role of KCNQ1OT1 in colorectal cancer remain unclear. Here, we show that the KCNQ1OT1 transcriptional level was significantly increased in human colorectal cancer cells in which β-catenin was excessively accumulated in the nucleus. Additionally, overexpression of β-catenin resulted in an increase in KCNQ1OT1 lncRNA-coated territory. On the other hand, knockdown of β-catenin resulted in significant decrease of KCNQ1OT1 lncRNA-coated territory and an increase in the mRNA expression of the SLC22A18 and PHLDA2 genes that are regulated by KCNQ1OT1. We showed that β-catenin can promote KCNQ1OT1 transcription through direct binding to the KCNQ1OT1 promoter. Our evidence indicates that β-catenin signaling may contribute to development of colorectal cancer by functioning as a novel lncRNA regulatory factor via direct targeting of KCNQ1OT1.

A real health problem of our days: Colorectal Cancer

Abstract Colorectal cancer is one of the major mortality causes in the world, with an increased frequency in western countries, which are better developed economically. Romanian statistics show that the frequency of this type of cancer is increasing rapidly. In the year 2000, all over the world there were approximately 1 million new cases of colorectal cancer, and over 500 thousands deaths, thus affecting 1 from 20 inhabitants from the developed countries and being the second main cancer death cause, at both sexes in Europe. In Romania, incidence and mortality have doubled in the last 20 years, reaching a 17.74/100000 inhabitants incidence in the year 2000. Both for men and women, this disease is on the 3rd place in Romania, after bronhopulmonary cancer and gastric (for men) and breast and uterus cancer, respectively. This paper has as purpose obtaining data about the frequency of colorectal cancer in recent years, and the repartition of this data on years, sex, age, environment, complications and other particularities. To reach this purpose we have done a retrospective study on patients that were admitted during 2010-2014 in the surgical clinic, medical clinic and oncology section from the Constanta Emergency County hospital, with colorectal neoplasm as a diagnosis.

Evaluation of an assay for methylated BCAT1 and IKZF1 in plasma for detection of colorectal neoplasia

BackgroundSpecific genes, such as BCAT1 and IKZF1, are methylated with high frequency in colorectal cancer (CRC) tissue compared to normal colon tissue specimens. Such DNA may leak into blood and be present as cell-free circulating DNA. We have evaluated the accuracy of a novel blood test for these two markers across the spectrum of benign and neoplastic conditions encountered in the colon and rectum.MethodsCirculating DNA was extracted from plasma obtained from volunteers scheduled for colonoscopy for any reason, or for colonic surgery, at Australian and Dutch hospitals. The extracted DNA was bisulphite converted and analysed by methylation specific real-time quantitative PCR (qPCR). A specimen was deemed positive if one or more qPCR replicates were positive for either methylated BCAT1 or IKZF1 DNA. Sensitivity and specificity for CRC were estimated as the primary outcome measures.ResultsPlasma samples were collected from 2105 enrolled volunteers (mean age 62 years, 54 % male), including 26 additional samples taken after surgical removal of cancers. The two-marker blood test was run successfully on 2127 samples. The test identified 85 of 129 CRC cases (sensitivity of 66 %, 95 % CI: 57–74). For CRC stages I-IV, respective positivity rates were 38 % (95 % CI: 21–58), 69 % (95 % CI: 53–82), 73 % (95 % CI: 56–85) and 94 % (95 % CI: 70–100). A positive trend was observed between positivity rate and degree of invasiveness. The colonic location of cancer did not influence assay positivity rates. Gender, age, smoking and family history were not significant predictors of marker positivity. Twelve methylation-positive cancer cases with paired pre- and post-surgery plasma showed reduction in methylation signal after surgery, with complete disappearance of signal in 10 subjects. Sensitivity for advanced adenoma (n = 338) was 6 % (95 % CI: 4–9). Specificity was 94 % (95 % CI: 92–95) in all 838 non-neoplastic pathology cases and 95 % (95 % CI: 92–97) in those with no colonic pathology detected (n = 450).ConclusionsThe sensitivity for cancer of this two-marker blood test justifies prospective evaluation in a true screening population relative to a proven screening test. Given the high rate of marker disappearance after cancer resection, this blood test might also be useful to monitor tumour recurrence.Trial registrationACTRN12611000318987.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1674-2) contains supplementary material, which is available to authorized users.

BRAF Gene Mutation Analysis in Colorectal Cancer in South of Iran

Background: Colorectal carcinoma is the third most commonly diagnosed cancer worldwide and many studies have focused on its molecular basis. BRAF V600E is the single most important mutation of this gene in cancers. It shows variable, but usually low, frequency in colorectal cancer, but is associated with distinct histologic, prognostic and molecular features. It is highly associated with MSI (microsatellite instability), CIMP-H (CpG island methylator phenotype), serrated pathway, poor prognosis and resistance to anti-EGFR (epidermal growth factor) drugs and interestingly absent in Lynch syndrome. Objectives: In this study, we analyzed BRAF V600E mutation in colorectal cancer in Iranian patients. Patients and Methods: One hundred patients with colorectal cancer, operated in hospitals affiliated to Shiraz University of medical Sciences (Faghihi and Namazi Hospital) were selected. The cases were chosen from the pathology files of the above mentioned hospitals, during 2011-2013. Genomic DNA were extracted from the paraffin blocks, by the DNP TM kit, amplified using conventional PCR and DNA sequenced using the automated sequencer (Sanger method). Results: Patients were 21-87 years old (mean = 59.8), 45% female and 55% male. Thirty percent of the cases had right-sided and 70% left-sided cancer, of which 83% were well and 17% moderately differentiated. No BRAF V600E mutation was detected in these 100 cases. Conclusions: The BRAF mutation is not common in colorectal cancer patients in the South of Iran. Our results are very similar to very few previous studies conducted in Iran, although we suggest further studies with larger numbers of patients to confirm these results.

A panel of genes methylated with high frequency in colorectal cancer.

BackgroundThe development of colorectal cancer (CRC) is accompanied by extensive epigenetic changes, including frequent regional hypermethylation particularly of gene promoter regions. Specific genes, including SEPT9, VIM1 and TMEFF2 become methylated in a high fraction of cancers and diagnostic assays for detection of cancer-derived methylated DNA sequences in blood and/or fecal samples are being developed. There is considerable potential for the development of new DNA methylation biomarkers or panels to improve the sensitivity and specificity of current cancer detection tests.MethodsCombined epigenomic methods – activation of gene expression in CRC cell lines following DNA demethylating treatment, and two novel methods of genome-wide methylation assessment – were used to identify candidate genes methylated in a high fraction of CRCs. Multiplexed amplicon sequencing of PCR products from bisulfite-treated DNA of matched CRC and non-neoplastic tissue as well as healthy donor peripheral blood was performed using Roche 454 sequencing. Levels of DNA methylation in colorectal tissues and blood were determined by quantitative methylation specific PCR (qMSP).ResultsCombined analyses identified 42 candidate genes for evaluation as DNA methylation biomarkers. DNA methylation profiles of 24 of these genes were characterised by multiplexed bisulfite-sequencing in ten matched tumor/normal tissue samples; differential methylation in CRC was confirmed for 23 of these genes. qMSP assays were developed for 32 genes, including 15 of the sequenced genes, and used to quantify methylation in tumor, adenoma and non-neoplastic colorectal tissue and from healthy donor peripheral blood. 24 of the 32 genes were methylated in >50% of neoplastic samples, including 11 genes that were methylated in 80% or more CRCs and a similar fraction of adenomas.ConclusionsThis study has characterised a panel of 23 genes that show elevated DNA methylation in >50% of CRC tissue relative to non-neoplastic tissue. Six of these genes (SOX21, SLC6A15, NPY, GRASP, ST8SIA1 and ZSCAN18) show very low methylation in non-neoplastic colorectal tissue and are candidate biomarkers for stool-based assays, while 11 genes (BCAT1, COL4A2, DLX5, FGF5, FOXF1, FOXI2, GRASP, IKZF1, IRF4, SDC2 and SOX21) have very low methylation in peripheral blood DNA and are suitable for further evaluation as blood-based diagnostic markers.

High methylation of the SEPT9 gene in Chinese colorectal cancer patients

Methylation of the septin 9 gene (SEPT9) occurs in higher frequency in colorectal cancer (CRC) compared to control samples, which suggests that SEPT9 methylation is a useful biomarker for screening CRC. However, the methylation status of SEPT9 in Chinese CRC patients is scarcely reported. In the present study, SEPT9 methylation was tested in CRC tissues obtained from a Chinese population and correlations with pathological characteristics were investigated. The methylation status of SEPT9 was detected using methylation-specific polymerase chain reaction (PCR)-denaturing high-performance liquid chromatography (MSP-DHPLC) in 234 colorectal tissues (172 cases, 62 controls). Samples were sequenced to confirm the results from MSP-DHPLC. The chi-squared test was used to analyze the correlation of SEPT9 gene methylation status and pathological characteristics in CRCs. SEPT9 gene methylation was detected in 152 of 172 (88.4%) cases of verified CRC and in 4 of 62 (6.5%) healthy controls (χ(2) = 137.62, P < 0.001). There was no association between the methylation status of SEPT9 and age, gender, Duke's stage, TNM stage, differentiation, and site of cancer (P > 0.05). Our results suggest that SEPT9 gene methylation is a valuable biomarker for screening CRC in the Chinese population.