Aspartyl (Asparaginyl) β-Hydroxylase AABH as a serum biomarker for colorectal cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 86-86
Author(s):  
Mahmood Moshiri ◽  
Kiarash Moshiri ◽  
Yasamin Farbod ◽  
Arsha Moshiri ◽  
Mohammad Hadi Sekhavati
Keyword(s):  
Colorectal Cancer ◽  
Blood Test ◽  
Sandwich Elisa ◽  
Survival Rates ◽  
Screening Methods ◽  
Cancer Society ◽  
Tissue Samples ◽  
Normal Individuals ◽  
Sandwich Elisa Assay ◽  
Cancer Network

86 Background: Colorectal Cancer (CRC) is the third most common type of cancer diagnosed in the US and Canada. WHO, Canadian Cancer Society (CCS), the National Comprehensive Cancer Network (NCCN) and American Cancer Society (ACS) recommend that men and women begin CRC screening at age 50 or younger if at high risk. Recommended screening procedures: Annual occult fecal blood test (OFBT), a colonoscopy every 5 years, OFBT and colonoscopy every 5 years, or a colonoscopy every 10 years. According to The Surveillance, Epidemiology, and End Results (SEER) Program, only 39% of CRC are diagnosed in stage I, 36% are diagnosed in Stage II, 19% are diagnosed with metastasis. The corresponding 5-year survival rates are 89.8%, 67.7%, and 10.3%. Neither the CCS nor the ACS recommends a blood test be done as part of screening. This is due to the fact that, until now, there has not been a blood test with adequate sensitivity or specificity for screening. Methods: In this study we discovered that Aspartyl (Asparaginyl) β-Hydroxylase (AABH) measurement in serum can be used as an screening test for CRC. AABH has been detected by immunohistochemical staining (IHC) on the cell surface of different cancers including CRC. It has been detected by IHC in > 97% of tumor specimens tested (n > 200) but has not been found in tissue samples from normal individuals. Results: This observation and the observation that AABH is found in the serum of patients with cancer, but not in n0n cancer patients, led us to develop a Sandwich ELISA Assay to measure AABH in serum. In the current study we have quantified AABH levels in CRC patients and compared it with normal individual. Increased levels of AABH were found in the serum of 91.5% of patients with CRC in all different stages of Cancer (n = 60). In normal individuals, AABH was essentially undetectable in serum (n = 30). AABH was identified in serum from patients with CRC irrespective of cancer stage. All serum AABH levels for stages I, II, III and IV were more than 3.3 ng/mL. Conclusions: Thus, our data indicate that by measuring AABH in the serum, we should be able to detect CC at an earlier stage than it is currently detected, resulting to a much better 5-year survival for CC.

AABH (aspartyl (asparaginyl) β-hydroxylase ) as a serum biomarker for colorectal cancer diagnosis and prognosis.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 22-22
Author(s):  
Mahmood Moshiri ◽  
Arsha Moshiri ◽  
Kiarash Moshiri
Keyword(s):  
Colorectal Cancer ◽  
Blood Test ◽  
Sandwich Elisa ◽  
Relative Survival ◽  
Primary Site ◽  
Fecal Occult Blood ◽  
Regional Lymph Nodes ◽  
Cancer Society ◽  
Tissue Samples ◽  
Blood Tests

22 Background: Colorectal cancer (CRC) is the third most common type of cancer diagnosed in the US. The National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS) recommend that men and women begin colorectal cancer screening at age 50 or younger if they are at high risk. One of the following screening procedures is recommended: tests for fecal blood annually, a colonoscopy every 5 years, fecal occult blood tests in conjunction with colonoscopy every 5 years, a double-contrast barium enema every 5 years or a colonoscopy every 10 years. Fecal blood tests and colonoscopy are preferred over either test alone. Despite these recommendations, according to The Surveillance, Epidemiology and End Results Data Base (SEER), only 41% of colon cancers are diagnosed when the cancer is still confined to its primary site, 36% are diagnosed when the tumor has spread directly from its primary site or to regional lymph nodes, 19% are diagnosed when the cancer has already metastasized (4% unknown). The corresponding 5-year relative survival rates are 89.8% for localized disease, 67.7% for regional disease, and 10.3% for metastatic disease. Methods: Neither the NCCN nor the ACS recommends that a blood test be done as part of screening. This is due to the fact that, until now, there has not been a blood test with adequate sensitivity or specificity for this purpose. We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a screening test for colorectal cancer. Results: AABH has been detected by immunohistochemical staining (IHC) on the cell surface of a broad range of cancers including CRC. It has been detected by IHC in > 99% of tumor specimens tested (n > 2300) but has not been found in adjacent normal tissue and in tissue samples from people who do not have cancer. This observation and the observation that AABH is found in the serum of patients with cancer, but not in the serum of people who are cancer-free, led the development of a sandwich ELISA to measure AABH in serum. In the current study we have utilized the serum assay to quantify AABH levels in patients diagnosed with CRC and compared these values with those of people who did not have a diagnosis of cancer. Increased levels of AABH were found in the serum of 99% of patients with CRC (n = 175). In individuals not known to have cancer, AABH was essentially undetectable in serum (n = 213, specificity = 96%). Conclusions: AABH was identified in serum from patients with CRC irrespective of stage. Serum AABH levels for stages I, II, III and IV (local, regional, advanced regional and metastatic) were higher than 0.30 ng/mL (Cut off level). Thus, our data indicate that by measuring AABH in the serum, we should be able to detect colorectal cancer in most individuals at an earlier stage than it is currently detected. Hence, we believe that the broad application of this test could result in a much better 5-year survival for the majority of patients with colorectal cancer.

scholarly journals Metabolomic profile of colorectal cancer patients and its clinical implications

2020 ◽  
Vol 25 (6) ◽  
pp. 2045-2054
Author(s):  
CLAUDIU RĂCHIERIU ◽  
◽  
FLORIN GRAUR ◽  
EMIL MOIS ◽  
CARMEN SOCACIU ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Diagnosis ◽  
Biological Fluids ◽  
Tumor Staging ◽  
Public Health Issue ◽  
Screening Methods ◽  
Tissue Samples ◽  
Medical Databases ◽  
Colorectal Cancer Patients

Background: Colorectal Cancer (CRC) is a great public health issue and the outcomes of treatment depends on early diagnosis. Metabolomics may provide biomarkers for early diagnosis, staging, prognosis and follow-up. Methods: The authors searched for the results of the published studies existing in medical databases (PubMed) for all the changes in the main metabolic pathways (carbohydrate, lipid, aminoacid, nucleotide and other important metabolites) of the CRC patients and how the metabolic changes can be used as biomarkers, for tumor staging, prognosis and follow-up. Results: While most of the metabolites values in biological fluids or tissue samples are modified (either increased or decreased) and the results are usually constant across the studies it seems that only patterns of metabolites (fingerprints of 5, 15 or even 30 metabolites) can be used for the regarding issues mentioned above. Conclusion: Some studies conclude that some metabolomic models are statistically much better than current existing markers and may become screening methods in the near future.

A novel, cost-effective strategy for the screening of colorectal cancer with higher patient compliance.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 407-407
Author(s):  
Afsaneh Motamed-Khorasani ◽  
Andrea Lee Small-Howard
Keyword(s):  
Colorectal Cancer ◽  
Patient Compliance ◽  
Blood Test ◽  
Early Stage ◽  
Cost Effective ◽  
Patient Treatment ◽  
Screening Methods ◽  
Crc Screening ◽  
Combined Test ◽  
Low Sensitivity

407 Background: Routine screening methods for colorectal cancer (CRC) have poor patient compliance and low sensitivity for early stages. The sensitivity rates are 19, 71, 76, and 83% for Fecal Occult Blood test (FOBT), stool DNA test, colonoscopy/sigmoidoscopy, and double-contrast barium enema; respectively. Biological markers have also been tested including CEA (sensitivity of 38.7%); however, its utility in CRC screening is limited due to low sensitivity. Onko-Sure is an FDA-cleared blood test for monitoring of CRC treatment/recurrence. It measures the accumulation of Fibrin/Fibrinogen Degradation products in the serum using anti-DR-70 antibody. The objective was to determine whether DR-70 and CEA combination can improve the sensitivity such that it can be used as a cost-effective alternative to current screening methods yet with a higher patient compliance. Methods: A total of 564 serum samples were retrospectively obtained from a serum bank in two arms: confirmed healthy control (n=298) and biopsy-confirmed CRC (n=266) groups. The samples were tested for DR-70 and CEA. Results: The results showed sensitivity of 58.2% and specificity of 59.83% for DR-70 and CEA combined. The sensitivity for the combined test was 55.5% higher than that of CEA alone. A consistent improvement of sensitivity for the combined usage relative to CEA alone was observed with an increase of 73%, 108%, 58% and 18% in CRC stage I, II, III and IV; respectively. The sensitivity of the combined test was 48%, 47%, 57% and 98% for stages I, II, III and IV. Conclusions: Combining DR-70 and CEA tests showed a significant clinical advantage in CRC screening over using each marker alone. The sensitivity improvement was highest for stages I/II, which has important implications in patient treatment options, prognosis and survival rate due to this early detection. With a 3 times higher sensitivity for early stage CRC compared to using FOBT, this approach should improve the CRC early stage diagnosis. Such early stage detection is less likely using routine approaches for CRC screening because of low sensitivity and low patient compliance.

scholarly journals Colorectal cancer screening: Barriers to the faecal occult blood test (FOBT) and colonoscopy in Singapore

2016 ◽  
Vol 25 (4) ◽  
pp. 207-214 ◽  
Author(s):  
Sook Kwin Yong ◽  
Whee Sze Ong ◽  
Gerald Choon-Huat Koh ◽  
Richard Ming Chert Yeo ◽  
Tam Cam Ha
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Blood Test ◽  
Screening Method ◽  
Occult Blood ◽  
Faecal Occult Blood Test ◽  
Screening Methods ◽  
Occult Blood Test ◽  
Crc Screening ◽  
Faecal Occult

Introduction: This study aims to identify the barriers to adopting faecal occult blood test (FOBT) and colonoscopy as colorectal cancer (CRC) screening methods among the eligible target population of Singapore. Materials and methods: This study was previously part of a randomised controlled trial reported elsewhere. Data was collected from Singapore residents aged 50 and above, via a household sample survey. The study recruited subjects who were aware of CRC screening methods, and interviewed them about the barriers to screening that they faced. Collected results on barriers to each screening method were analysed separately. Results: Out of the 343 subjects, 85 (24.8%) recruited knew about FOBT and/or colonoscopy. Most of the respondents (48.9%) cited not having symptoms as the reason for not using the FOBT. This is followed by inconvenience (31.1%), not having any family history of colon cancer (28.9%), lack of time (28.9%) and lack of reminders/recommendation (28.9%). Of the respondents who indicated not choosing colonoscopy as a screening method, more than one-half (54.8%) identified not having any symptoms as the main barrier for them, followed by not having any family history (38.7%) and having a healthy/low-risk lifestyle (29.0%). There was no difference between the reported barriers to each of the screening methods and the respondents’ dwelling types. Conclusions: Lack of knowledge, particularly the misconceptions of not having symptoms and being healthy, were identified as the main barriers to FOBT and colonoscopy as screening methods. Interventions to increase the uptake of CRC screening in this population should be tailored to address this misconception.

scholarly journals MicroRNAs as non-invasive screening biomarkers of colorectal cancer

2015 ◽  
Vol 88 (4) ◽  
pp. 453-456 ◽  
Author(s):  
Roberta Maria Manzat Saplacan ◽  
Petru Adrian Mircea ◽  
Loredana Balacescu ◽  
Ovidiu Balacescu
Keyword(s):  
Colorectal Cancer ◽  
Cancer Detection ◽  
Blood Test ◽  
Cost Effective ◽  
Screening Methods ◽  
Circulating Microrna ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Diagnostic Potential ◽  
The World

Colorectal cancer is a major cause of cancer-associated deaths in the world. Early detection would be greatly enhanced if accurate and cost-effective diagnostic biomarkers for this disease were accessible. The development of such a blood test will evidently lower the screening costs in regards of colorectal cancer detection. Lately, it has been suggested that microRNA diagnostic biomarkers are feasible new screening methods for colorectal cancer. This review summarizes the diagnostic potential of circulating microRNA biomarkers in relation with colorectal cancer, as well as current methods to detect them. 

Tumor marker CA 11-19 as a new serum blood test for monitoring colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 536-536
Author(s):  
John J. Costanzi ◽  
Tommye Ann Jordan ◽  
Lisa Jensen-long
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Tumor Marker ◽  
Sensitivity And Specificity ◽  
Blood Test ◽  
Sandwich Elisa ◽  
Fecal Occult Blood ◽  
Increased Risk

536 Background: Colorectal cancer remains the third most frequent cause of cancer deaths globally. The FOBT (fecal occult blood test) and FIT (fecal immunochemical test) as well as CEA are increasingly being used to screen or monitor patients at increased risk for colorectal cancer (CRC), however none has optimal performance in terms of both sensitivity and specificity. Data was recently published* on the new serum blood test colorectal tumor marker CA11-19. This data showed a sensitivity of 98% (95% CI, 93.1%-99.5%) and specificity of 84% (95% CI, 80.0%-87.9%) at a cut-off value of 6.5 U/mL with a high sensitivity for detection of early stage CRC as opposed to CEA whose values are reported ~40% and ~30–80%** respectively for sensitivity and specificity. This study will look at case studies that show an array of long-term monitoring outcomes which suggest possible use of CA 11-19 instead of CEA. Methods: Using a sandwich ELISA assay, a new colon cancer antigen, CA 11-19, (100 kDa glycoprotein) was measured in samples of 7 patients with a variety of conditions in normal, benign GI diseases, polyps and colon cancer. This long-term follow up is recorded from 8 to 20 years. Results: Serum samples previously frozen were used to measure the CA11-19 antigen. An average follow up time of 15 years (range 8 to 20 years) was recorded. Elevated levels of CA11-19 were detected in patients with polyps and CRC prior to treatment and decreased levels were measured after the removal of the polyps or cancer. Importantly, rising rates of CA11-19 were seen in patients with cancer recurrences of colorectal cancers. Conclusions: CA 11-19 is a serologic tumor marker for colorectal cancer with a published sensitivity of 97.7% and a specificity of 84.4%*. Preliminary reports from 7 cases show long-term data which could be more helpful in monitoring and or follow-up of high risk patients for CRC than the current CEA testing method. Additional studies are needed to further validate the use of CA 11-19 in these patient groups.

scholarly journals Association between colorectal cancer and Fusobacterium nucleatum and Bacteroides fragilis bacteria in Iranian patients: a preliminary study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Abundance ◽  
Normal Tissue ◽  
Bacteroides Fragilis ◽  
Fusobacterium Nucleatum ◽  
Normal Mucosa ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Adjacent Normal Mucosa ◽  
Iranian Patients

Abstract Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.

scholarly journals Immunohistochemical expression of β-catenin, Ki67, CD3 and CD18 in canine colorectal adenomas and adenocarcinomas

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Kristin M. V. Herstad ◽  
Gjermund Gunnes ◽  
Runa Rørtveit ◽  
Øyvor Kolbjørnsen ◽  
Linh Tran ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Colorectal Adenomas ◽  
Colorectal Carcinogenesis ◽  
Positive Staining ◽  
Colonic Tissue ◽  
Retrospective Case ◽  
Tissue Samples ◽  
Colonic Cells ◽  
Control Samples

Abstract Background Inflammation is believed to influence human colorectal carcinogenesis and may have an impact on prognosis and survival. The mucosal immunophenotype in dogs with colorectal cancer is poorly described. The aim of this study was to investigate whether the density, distribution and grade of tumor-infiltrating immune cells (TIIs) are different in normal colonic tissue vs benign stages (adenomas) and malignant stages (adenocarcinomas) of canine colorectal carcinogenesis, and thus, whether they can be considered as prognostic factors in dogs. This retrospective case-control study was performed on formalin-fixed, paraffin-embedded tissue samples from dogs with histologically confirmed colorectal adenoma (n = 18) and adenocarcinoma (n = 13) collected from archived samples. The samples had been collected by colonoscopy, surgery or during postmortem examination. Healthy colonic tissue obtained post mortem from dogs euthanized for reasons not involving the gastrointestinal tract served as control tissue (n = 9). Results The tumor samples had significantly lower numbers of CD3+ T-cells in the epithelium compared to controls (adenocarcinoma vs control, Kruskal-Wallis test, p = 0.0004, and adenoma vs control, p = 0.002). Adenomas had a significantly lower number of CD18+ cells in the lamina propria, compared to control samples (Kruskal-Wallis test, p = 0.008). Colonic samples from control dogs had uniform staining of β-catenin along the cell membrane of epithelial cells. Compared to normal colonic cells, the expression levels of cytoplasmic β-catenin were significantly higher in adenomas and adenocarcinomas (adenoma vs control Kruskal-Wallis test, p = 0.004, and adenocarcinoma vs control, p = 0.002). None of the control samples showed positive staining of β-catenin in the nucleus of colonic cells. In contrast, adenocarcinomas and adenomas showed moderate to strong staining of the cell nucleus. The nuclear β-catenin expression (signal strength and distribution) was significantly higher in adenomas compared to adenocarcinomas (Kruskal-Wallis test, p < 0.05). Conclusions β-catenin and Ki67 were not useful markers for demonstrating tumor progression from adenomas to adenocarcinomas. The lower presence of CD18 and CD3+ cells in colorectal tumors compared to controls indicates a reduced presence of histiocytes and T-cells, which may have implications for the pathogenesis and progression of colorectal cancer in dogs.

scholarly journals German oncology certification system for colorectal cancer – relative survival rates of a single certified centre vs. national and international registry data

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maximilian Richter ◽  
Lena Sonnow ◽  
Amir Mehdizadeh-Shrifi ◽  
Axel Richter ◽  
Rainer Koch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
International Comparison ◽  
Cancer Registry ◽  
Survival Data ◽  
Survival Rates ◽  
Relative Survival ◽  
Registry Data ◽  
Cancer Registry Data ◽  
Colon And Rectal Cancer

Abstract Objectives To evaluate how the certification of specialised Oncology Centres in Germany affects the relative survival of patients with colorectal cancer (CRC) by means of national and international comparison. Methods Between 2007 and 2013, 675 patients with colorectal cancer, treated at the Hildesheim Hospital, an academic teaching hospital of the Hannover Medical School (MHH), were included. A follow-up of the entire patient group was performed until 2014. To obtain international data, a SEER-database search was done. The relative survival of 148,957 patients was compared to our data after 12, 36 and 60 months. For national survival data, we compared our rates with 41,988 patients of the Munich Cancer Registry (MCR). Results Relative survival at our institution tends to be higher in advanced tumour stages compared to national and international cancer registry data. Nationally we found only little variation in survival rates for low stages CRC (UICC I and II), colon, and rectal cancer. There were notable variations regarding relative survival rates for advanced CRC tumour stages (UICC IV). These variations were even more distinct for rectal cancer after 12, 36 and 60 months (Hildesheim Hospital: 89.9, 40.3, 30.1%; Munich Cancer Registry (MCR): 65.4, 28.7, 16.6%). The international comparison of CRC showed significantly higher relative survival rates for patients with advanced tumour stages after 12 months at our institution (77 vs. 54.9% for UICC IV; raw p<0.001). Conclusions Our findings suggest that patients with advanced tumour stages of CRC and especially rectal cancer benefit most from a multidisciplinary and guidelines-oriented treatment at Certified Oncology Centres. For a better evaluation of cancer treatment and improved national and international comparison, the creation of a centralised national cancer registry is necessary.

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