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Impact of RAS and BRAF mutations on carcinoembryonic antigen production and pattern of colorectal metastases

World Journal of Gastrointestinal Oncology 2016年第1期8卷 128-135页

作者： may cho chie akiba cecilia lau david smith milhan telatar michelle afkhami stephen sentovich kurt melstrom marwan fakih department of medical oncology city of hope national medical centerDuarteCA 91010United States department of statistics city of hope national medical centerDuarteCA 91010United States department of pathology city of hope national medical centerDuarteCA 91010United States department of surgical oncology city of hope national medical centerDuarteCA 91010United States

AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen(CEA) ***: In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer(CRC) were included. Patients' characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF ***: Among 174 patients, mutations in KRAS, NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations(KRAS and NRAS) were more likely to be found in African American patients(87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA(< 5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm any association between mutational status and site of metastatic disease at initial ***: No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Patients with RAS mutations were more likely to present with CEA levels < 5 ng/mL. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.

关键词： RAS BRAF carcinoembryonic antigen Pattern of metastatic disease Surveillance

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Micro-plate magnetic chemiluminescence immunoassay and its applications in carcinoembryonic antigen analysis

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Science China Chemistry 2010年第4期53卷 812-819页

作者： LI ZhiYong1, ZHANG QianYun2, ZHAO LiXia1, LI ZhenJia3, HU GuoMao3, LIN Jin-Ming2 & WANG Shan4 1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China 2Department of Chemistry, Tsinghua University, Beijing 100084, China 3Beijing Chemclin Biotech Co., Ltd., Beijing Academy of Science and Technology, Beijing 100094, China 4School of Chemistry and Chemical Engineering, Xianyang Normal College, Xianyang 712000, China 1. State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beijing 100085 China2. Department of Chemistry Tsinghua University Beijing 100084 China3. Beijing Chemclin Biotech Co. Ltd. Beijing Academy of Science and Technology Beijing 100094 China4. School of Chemistry and Chemical Engineering of Xianyang Normal College Xianyang 712000 China

A micro-plate magnetic chemiluminescence immunoassay was developed for rapid and high throughput detection of carcinoembryonic antigens (CEA) in human sera. This method was based on a sandwich immunoreaction of fluorescein isothiocyanate (FITC)-labeled anti-CEA antibodies, CEA antigens, and horseradish peroxidase (HRP)-conjugated anti-CEA antibodies in mi- cro-plate. The immunomagnetic particles coated with anti-FITC antibodies were used as the solid phase for the immunoassay. The separation procedure was carried out by a magnetic plate adaptor and the luminol-hydrogen peroxide (H2O2)-HRP system was employed for the chemiluminescence detection. The proposed method combined the advantages of the micro-plate reactor and magnetic particle separation technology with the linear range of 5-250 ng mL·1. The detection limit of CEA was 0.61 ng mL·1. The coefficient of the variation was less than 7% and 13% for intra-assay and inter-assay precision, respectively. Compared with the commercial micro-plate chemiluminescent kit, the proposed method showed a good correlation.

关键词： micro-plate magnetic chemiluminescence immunoassay carcinoembryonic antigen tumor marker

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Determination of carcinoembryonic antigen using a novel amperometric enzyme-electrode based on layer-by-layer assembly of gold nanoparticles and thionine

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Science China Chemistry 2007年第1期50卷 97-104页

作者： YUAN Ruo ZHUO Ying CHAI YaQin ZHANG Ying SUN AiLi Chongqing Key Laboratory of Analytical Chemistry College of Chemistry and Chemical EngineeringSouthwest UniversityChongqing 400715China

Electrochemical sensing of carcinoembryonic antigen(CEA)on a gold electrode modified by the se- quential incorporation of the mediator,thionine(Thi),and gold nanoparticles(nano-Au),through co- valent linkage and electrostatic interactions onto a self-assembled monolayer configuration is de- scribed in this *** enzyme,horseradish peroxidase(HRP),was employed to block the possible remaining active sites of the nano-Au monolayer,avoid the non-specific adsorption,instead of bovine serum albumin(BSA),and amplify the response of the antigen-antibody *** ex- periments indicated highly efficient electron transfer by the imbedded Thi mediator and adsorbed *** HRP kept its activity after immobilization,and the studied electrode showed sensitive response to CEA and high stability during a long period of *** working range for the system was 2.5 to 80.0 ng/mL with a detection limit of 0.90 ng/*** model membrane system in this work is a potential biosensor for mimicking the other immunosensor and enzyme sensor.

关键词： immunosensor gold nanoparticles(nano-Au) thionine(Thi) carcinoembryonic antigen(CEA) horseradish peroxidase(HRP) layer-by-layer(LBL)

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Cyst fluid glucose: An alternative to carcinoembryonic antigen for pancreatic mucinous cysts

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World Journal of Gastroenterology 2019年第19期25卷 2271-2278页

作者： César Vivian Lopes Department of Gastroenterology and Digestive Endoscopy Santa Casa Hospital

Pancreatic cystic lesions(PCLs) have been increasingly recognized in clinical practice. Although inflammatory cysts(pseudocysts) are the most common PCLs detected by cross-sectional imaging modalities in symptomatic patients in a setting of acute or chronic pancreatitis, incidental pancreatic cysts with no symptoms or history of pancreatitis are usually neoplastic cysts. For these lesions,it is imperative to identify mucinous cysts(intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) due to the risk of their progression to malignancy. However, no single imaging modality alone is sufficient for a definitive diagnosis of all PCLs. The cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration provides additional information for the differential diagnosis of PCLs. Current recommendations suggest sending cyst fluid for cytology evaluation and measurement of carcinoembryonic antigen(CEA) levels. Unfortunately, the sensitivity of cytology is greatly limited, and cyst fluid CEA has demonstrated insufficient accuracy as a predictor of mucinous cysts. More recently, cyst fluid glucose has emerged as an alternative to CEA for distinguishing between mucinous and nonmucinous lesions. Herein, the clinical utility of cyst fluid glucose and CEA for the differential diagnosis of PCLs was evaluated.

关键词： carcinoembryonic antigen Differential diagnosis Fine-needle biopsy Glucose Pancreatic cyst Tumor marker

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Prognostic value of preoperative carcinoembryonic antigen/tumor size in rectal cancer

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World Journal of Gastroenterology 2019年第33期25卷 4945-4958页

作者： Du Cai Zeng-Hong Huang Hui-Chuan Yu Xiao-Lin Wang Liang-Liang Bai Guan-Nan Tang Shao-Yong Peng Ying-Jie Li Mei-Jin Huang Guang-Wen Cao Jian-Ping Wang Yan-Xin Luo Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease(Supported by National Key Clinical Discipline)The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655Guangdong ProvinceChina Department of Colorectal Surgery The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655Guangdong ProvinceChina Department of Biochemistry and Molecular Medicine School of MedicineUniversity of CaliforniaDavisSacramentoCA 95817United States Department of Epidemiology Second Military Medical UniversityShanghai 200433China

BACKGROUND carcinoembryonic antigen(CEA)is a commonly used biomarker in colorectal ***,controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal ***,we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level,which may better reflect the malignancy of rectal *** To assess the prognostic impact of preoperative CEA/tumor size in rectal *** We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to *** patients were randomly divided into two cohorts for cross-validation:training cohort and validation *** training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the *** selected rank statistics were used to identify the optimum cutoff for CEA/tumor *** Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival *** and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor *** primary and secondary outcomes were overall survival(OS)and disease-free survival(DFS),*** In all,556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort(2/3 of 556,n=371)and the validation cohort(1/3 of 556,n=185).The cutoff was 2.429 ng/mL per *** of the baseline data showed that high CEA/tumor size was correlated with older age,high TNM stage,the presence of perineural invasion,high CEA,and high carbohydrate antigen 19-9(CA 19-9).Kaplan-Meier curves showed a manifest reduction in 5-year OS(training cohort:56.7%vs 81.1%,P<0.001;validation cohort:58.8%vs 85.6%,P<0.001)and DFS(training cohort:52.5%vs 71.9%,P=0.02;validation cohort:50.3%vs 79.3%,P=0.002)in the high CEA/tumor size group compared with the low CEA/tumor size *** an

关键词： carcinoembryonic antigen carcinoembryonic antigen/tumor size Rectal cancer Prognosis Survival analysis

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prognostic significance of pretreatment serum carcinoembryonic antigen levels in gastric cancer with pathological lymph node-negative: A large sample singlecenter retrospective study

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World Journal of Gastroenterology 2017年第48期23卷 8562-8569页

作者： Jun Xiao Zai-Sheng Ye Sheng-Hong Wei Yi Zeng Zhen-Meng Lin Yi Wang Wen-Hao Teng Lu-Chuan Chen Department of Gastrointestinal Surgery Fujian Cancer Hospital and Fujian Medical University Cancer Hospital

AIM To assess whether elevated serum carcinoembryonic antigen(CEA) is in the inferior prognosis for pathological lymph node-negative(p N_0) gastric cancer(GC) patients who underwent D_2 *** About 469 p N0 GC patients,who received D^2 radical gastrectomy were retrospectively analyzed. The X-tile plots cut-off point for CEA were 30.02 ng/m L using minimum P-value from log-rank χ~2 statistics,and p N_0 GC patients were assigned to two groups: those more than 30.02 ng/m L(n = 48;CEA-high group) and those less than 30.02 ng/m L(n = 421;CEA-low group). Clinicopathologic characteristics were compared usingPearson's χ2 or Fisher's exact tests,and survival curves were so manufactured using the Kaplan-Meier method. Univariate and multivariate analysis were carried out using the logistic regression *** The percentage of vessel carcinoma embolus(31.35% vs 17.1%) and advanced GC(T_(2-4b))(81.25% vs 65.32%) were higher in CEA-high group than CEA-low group. The CEA-positive patients had a significantly poorer prognosis than the CEA-nagetive patients in terms of overall survival(57.74% vs 90.69%,P 0.05). Multivariate survival analysis showed that CEA(OR = 4.924),and T category(OR = 2.214) were significant prognostic factors for stage p N0 GC(all P < 0.05). Besides,only T category(OR = 1.962) was an independent hazard factor in the CEA-high group(P < 0.05).CONCLUSION Those pretreatment serum CEA levels over 30.02 ng/m L on behalf of worse characteristics and unfavourable tumor behavior,and a poor prognosis for a nearly doubled risk of mortality in GC patients.

关键词： carcinoembryonic antigen Gastric cancer Pathological lymph node-negative X-tile plots 5-year survial rate

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Preoperative carcinoembryonic antibody is predictive of distant metastasis in pathologically T1 colorectal cancer after radical surgery

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World Journal of Gastroenterology 2013年第3期19卷 389-393页

作者： Zheng Lou Rong-Gui Meng Wei Zhang En-Da Yu Chuan-Gang Fu Department of Colorectal Surgery Changhai Hospital

AIM:To identify the predictors of distant metastasis in pathologically T1(pT1)colorectal cancer(CRC)after radical resection. METHODS:Variables including age,gender,preoperative carcinoembryonic antibody(CEA)level,tumor location,tumor size,lymph node status,and histological grade were *** with and without metastasis were compared with regard to age,gender,CEA level and pathologic tumor characteristics using the independent t test orχ 2 test,as *** factors were determined by logistic regression analysis. RESULTS:Metastasis occurred in 6(3.8%)of the 159 patients during a median follow-up of 67.0(46.5%) *** rates of distant metastasis in patients with pT1 cancer of the colon and rectum were 6.7%and 2.9%, respectively(P<0.001).The rates of distant metastasis between male and female patients with T1 CRC were 6.25%and 1.27%,respectively(P<0.001).The most frequent site of distant metastasis was the liver. Age(P=0.522),gender(P=0.980),tumor location(P =0.330),tumor size(P=0.786),histological grade(P =0.509),and high serum CEA level(P=0.262)were not prognostic factors for lymph node *** analysis revealed that age(P=0.231),gender(P =0.137),tumor location(P=0.386),and tumor size (P=0.514)were not risk factors for distant metastasis after radical resection for T1 colorectal *** metastasis was only significantly correlated with high preoperative serum CEA level(P=0.001).Using multivariate logistic regression analysis,high preoperative serum CEA level(P=0.004;odds ratio 15.341; 95%CI 2.371-99.275)was an independent predictor for postoperative distant metastasis. CONCLUSION:The preoperative increased serum CEA level is a predictive risk factor for distant metastasis in CRC patients after radical *** chemotherapy may be necessary in such patients,even if they have pT1 colorectal cancer.

关键词： Colorectal cancer Risk factor Metastasis Pathologically T1 carcinoembryonic antigen

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Prognostic factors in resectable cholangiocarcinoma patients: carcinoembryonic antigen, lymph node, surgical margin and chemotherapy

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World Journal of Gastrointestinal Oncology 2013年第4期5卷 81-87页

作者： Kosin Wirasorn Thundon Ngamprasertchai Jarin Chindaprasirt Aumkhae Sookprasert Narong Khantikaew Ake Pakkhem Piti Ungarereevittaya Department of Medicine Khon Kaen University Department of Surgery Khon Kaen University Department of Pathology Khon Kaen University

AIM: To evaluate outcomes in resectable cholangiocarcinoma patients and to determine prognostic factors. METHODS: A retrospective study was conducted among newly-diagnosed cholangiocarcinoma patients from January 2009 to December 2011 who underwent curative resection in Srinakarind Hospital (a 1000-bed university hospital). Two hundred and sixty-three cholangiocarcinoma patients with good performance were enrolled. These patients had pathological reports with clear margins or microscopic margins. Prognostic factors which included clinical factors, serum liver function test as well as serum tumor makers at presentation,tumor data, and receiving adjuvant chemotherapy were determined by uniand multivariate analysis. RESULTS: The median overall survival time was 17 mo (95%CI: 13.2-20.7); and 1-, 2-, and 3year survival rates were 65.5%, 45.2% and 35.4%. Serum albumin levels, serum carcinoembryonic antigen (CEA) levels, staging classifications by American Joint Committee on cancer, pathological tumor staging, lymph node metastases, tumor grading, surgical margin status, and if adjuvant chemotherapy was administered, were shown to be significant prognostic factors of resectable cholangiocarcinoma by univariate analysis. Multivariate analysis, however, established that only abnormal serum CEA [hazard ratio (HR) 1.68; P = 0.027] and lymph node metastases (HR 2.27; P = 0.007) were significantly associated with a decrease in overall survival, while adjuvant chemotherapy (HR 0.71; P = 0.067) and surgical margin negative (HR 0.72; P = 0.094) tended to improve survival time. CONCLUSION: Serum CEA and lymph node metastases which were associated with advanced stage tumors become strong negative prognostic factors in cholangiocarcinoma.

关键词： Cholangiocarcinoma Prognosis carcinoembryonic antigen Lymph nodes Neoplasm metastasis Surgical margin status Hepatectomy Chemotherapy Adjuvant Survival rate

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carcinoembryonic Antigen as a Prognostic Factor in Colorectal Cancer with Liver Metastases

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Journal of Cancer Therapy 2015年第12期6卷 1035-1044页

作者： George E. McNally David M. Lloyd Jorge P. Grondona College of Medical and Dental Sciences University of Birmingham Birmingham UK Department of Hepatobiliary and Pancreatic Surgery University Hospitals of Leicester Leicester UK Department of Surgery Centro Medico de San Isidro Buenos Aires Argentina

Aim: The objective of this study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA) level in colorectal cancer patients with liver metastases. The serum CEA level was recorded at the point of metastasis diagnosis, differing from the majority of literature looking at preoperative metastasectomy CEA level. Methods: From January 2010 to December 2014, 138 patients with a diagnosis of colorectal cancer and liver metastases were included in the study—population from Buenos Aires, Argentina. Patients with both resectable and unresectable liver metastases were followed up over a 4-year period. Kaplan Meier survival analysis was used to produce survival curves that were compared by log-rank test. Results: The overall survival for all patients studied with a CEA < 100 ng/ml was significantly longer compared to patients with CEA ≥ 100 ng/mL (p < 0.001). The 1-, 2-, and 3-year overall survival rates for the whole cohort were 73.6, 56.6 and 53.8% respectively. For patients with unresectable metastases, a low CEA level (<100 ng/mL) was also associated with the increased overall survival (p = 0.036). Conclusions: In our patient cohort, this study indicated that a low CEA level (<100 ng/mL) measured at metastasis diagnosis was a good prognostic indicator for improving survival in patients with colorectal liver metastases. These findings highlight the importance of measuring serum CEA levels in this group of patients at the time of liver metastasis diagnosis.

关键词： carcinoembryonic Antigen (CEA) Colorectal Cancer Survival Liver Metastasis Postoperative Mortality

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Expression of Mammaglobin and carcinoembryonic Antigen in Peripheral Blood of Patients with Breast Cancer Using Real Time Polymerase Chain Reaction

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Open Journal of Clinical Diagnostics 2017年第4期7卷 103-112页

作者： Negin Khosravi Naghmeh Bahrami Adnan Khosravi Atefeh Abedini Arda Kiani Somayeh Sharifynia Pegah Gharaeeyan Sharareh Seifi Abdolreza Mohamadnia Islamic Azad University Tehran Iran Craniomaxillofacial Research Center Tehran University of Medical Sciences Tehran Iran Oral and Maxillofacial Surgery Department School of Dentistry Tehran University of Medical Sciences Tehran Iran Iranian Tissue Bank & Research Center Tehran University of Medical Sciences Tehran Iran Tobacco Prevention and Control Research Center National Research Institute of Tuberculosis and Lung Diseases (NRITLD) Shahid Beheshti University of Medical Sciences Tehran Iran Tracheal Diseases Research Center National Research Institute of Tuberculosis and Lung Diseases (NRITLD) Shahid Beheshti University of Medical Sciences Tehran Iran Clinical Tuberculosis and Epidemiology Research Center National Research Institute of Tuberculosis and Lung Diseases (NRITLD) Shahid Beheshti University of Medical Sciences Tehran Iran Chronic Respiratory Diseases Research Center National Research Institute of Tuberculosis and Lung Diseases (NRITLD) Shahid Beheshti University of Medical Sciences Tehran Iran Virology Research Center National Research Institute of Tuberculosis and Lung Diseases (NRITLD) Shahid Beheshti University of Medical Sciences Tehran Iran Department of Biotechnology School of Advanced Technologies in Medicine Shahid Beheshti University of Medical Sciences Tehran Iran

Background and Objectives: Breast cancer is among the most common causes of cancer related mortality in women worldwide. Early detection and prompt diagnosis of tumor is the first step to prevent cancer-related morbidity and mortality, and a comprehensive understanding of the involved molecular mechanisms can greatly help in this respect. Breast cancer, like many other types of cancer, is caused by a combination of genetic and epigenetic changes such as inactivation of tumor suppressor genes. Materials and Methods: This study was performed on 40 breast cancer patients and 40 healthy controls. Quantitative real time reverse transcription polymerase chain reaction (real time qRT-PCR) was used to assess the expression of carcinoembryonic antigen (CEA) and mammaglobin mRNA in the peripheral blood of patients and healthy controls. The two groups were compared using t-test. Results: The two groups were not significantly different in terms of the mean age. Twenty-nine out of 40 cancer patients were positive for CEA mRNA and its sensitivity was calculated to be 72.5%. Twelve out of 40 healthy controls were positive for CEA mRNA. Twenty-six out of 40 patients were positive for mammaglobin mRNA indicative of 65% sensitivity while only five out of 40 healthy controls were positive for mammaglobin mRNA. Conclusion: Both CEA and mammaglobin mRNA had high sensitivity in cancer patients;thus, they can be used for screening and early detection of breast cancer patients. Further studies with larger sample sizes are required to confirm the current findings.

关键词： Breast Cancer Biomarker Mammaglobin mRNA carcinoembryonic Antigen mRNA

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