Significance of carcinoembryonic antigen detection in the early diagnosis of colorectal cancer:A systematic review and metaanalysis

BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor involving adenomas that develop into malignant lesions.Carcinoembryonic antigen(CEA)is a non-specific serum biomarker upregulated in CRC.The concentration of CEA is modulated by tumor stage and grade,tumor site in the colon,ploidy status,and patient smoking status.This study aimed to evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.AIM To evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.METHODS A systematic search was performed using four databases:MEDLINE,Cochrane Trials,EMBASE,and the Web of Science.The inclusion criteria were as follows:Adult patients aged≥18 years who had completed CRC curative treatment and were followed up postoperatively;reporting the number of CRC recurrences as an outcome;and randomized,clinical,cohort,and case-control study designs.Studies that were not published in English and animal studies were excluded.The following data were extracted by three independent reviewers:Study design,index tests,follow-up,patient characteristics,and primary outcomes.All statistical analyses were performed using the RevMan 5.4.1.RESULTS A total of 3232 studies were identified,with 73 remaining following the elimination of duplicates.After screening on predetermined criteria,12 studies were included in the final analysis.At a reference standard of 5 mg/L,CEA detected only approximately half of recurrent CRCs,with a pooled sensitivity of 59%(range,33%–83%)and sensitivity of 89%(range,58%–97%).CONCLUSION CEA is a significant marker for CRC diagnosis.However,it has insufficient sensitivity and specificity to be used as a single biomarker of early CRC recurrence,with an essential proportion of false negatives.

Carcinoembryonic antigen,carbohydrate antigen 199 and carbohydrate antigen 724 in gastric cancer and their relationship with clinical prognosis

BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system with a high degree of malignancy.It usually develops insidiously without any specific symptoms in the early stages.As one of the diseases caused by abnormal gene changes,GC has abnormal expression of various oncogenes and products during its development.Tumor markers such as carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and carbohydrate antigen 724(CA724)are not expressed or lowly expressed in normal people,but significantly increased after carcinogenesis.Monitoring the changes in the levels of tumor markers such as CEA,CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors.AIM To investigate the expression of CEA,CA199 and CA724 in GC and their correlation with clinical features,hoping to provide more effective markers for the early preventive diagnosis of GC.METHODS Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group,and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group.The serum CEA,CA199,and CA724 levels were compared between the two groups,and the serum CEA,CA199,and CA724 levels were compared in patients with GC at different TNM stages,and the differences in the positive rates of CEA,CA199,and CA724 alone and in combination in detecting TNM stages of GC and GC were compared.In addition,the relationship between the levels of tumor markers CEA,CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed.The relationship between the serum levels of CEA,CA199 and CA724 and the survival period of GC patients was analyzed by Pearson.RESULTS The serum levels of CEA,CA199 and CA724 in GC group were significantly higher than those in control group(P<0.05).With the increase of TNM stage,the serum CEA,CA199 and CA724 expression levels in GC patients increased significantly,and the differences between groups were statistically significant(P<0.05).The positive rate of the CA724 single test was higher than that of CEA and CA199 single test(P<0.05).The positive rate of the three combined tests was 95.40%(83/87),which was higher than that of CEA,CA199 and CA724 single tests.The difference was statistically significant(P<0.05).The combined detection positive rates of CEA,CA199,and CA724 in stages I,II,III,and IV of GC were 89.66%,93.10%,98.85%,and 100.00%respectively,all of which were higher than the individual detection rates of CEA,CA199,and CA724.The differences were statistically significant(P<0.05).There was no significant difference in serum CEA,CA199 and CA724 levels between GC patients with different genders,smoking history and alcohol history(P>0.05).However,the serum CEA,CA199 and CA724 levels were significantly higher in GC patients aged≥45 years,TNM stage III-IV,with lymph node metastasis and tumor diameter≥5 cm than in GC patients aged<45 years,TNM stage I-II,without lymph node metastasis and tumor diameter<5 cm(P<0.05).CONCLUSION The expression levels of serum tumor markers CEA,CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage.The levels of CEA,CA199 and CA724 are related to age,TNM stage,lymph node metastasis and tumor diameter.The combined detection of CEA,CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.

Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis:A meta-analysis

BACKGROUND Carcinoembryonic antigen(CEA)is a broad-spectrum tumor marker for differential diagnosis,monitoring,and response assessment of a variety of malignancies.AIM To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis(CRCLM)before and after liver resection(LR).METHODS PubMed,Embase,Cochrane,and Web of Science were systematically searched to retrieve literature,with a search cut-off date of February 27,2023.Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria.Data were pooled and analyzed using Stata 16.0.RESULTS This meta-analysis included 36 studies involving a total of 11143 CRCLM patients.The results showed that a high pre-LR serum CEA level was correlated with poor overall survival(OS)[hazard ratio(HR)=1.61,95%confidence interval(CI):1.49-1.75,P<0.001]and recurrence-free survival(HR=1.27,95%CI:1.11-1.45,P<0.001)in CRCLM patients.A high post-LR serum CEA level predicted poor OS(HR=2.66,95%CI:2.10-3.38,P<0.001).A comparison by treatment modality,analysis modality,patient source,and cutoff-value showed that overall,high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis.CONCLUSION This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.

Prognostic value of changes in serum carcinoembryonic antigen levels for preoperative chemoradiotherapy response in locally advanced rectal cancer

BACKGROUND Preoperative chemoradiotherapy(CRT)is a standard treatment modality for locally advanced rectal cancer.However,CRT alone cannot improve overall survival.Approximately 20%of patients with CRT-resistant tumors show disease progression.Therefore,predictive factors for treatment response are needed to identify patients who will benefit from CRT.We theorized that the prognosis may vary if patients are classified according to pre-to post-CRT changes in carcinoembryonic antigen(CEA)levels.AIM To identify patients with locally advanced rectal cancer for preoperative chemoradiotherapy based on carcinoembryonic antigen levels.METHODS We retrospectively included locally advanced rectal cancer patients who underwent preoperative CRT and curative resection between 2011 and 2017.Patients were assigned to groups A,B,and C based on pre-and post-CRT serum CEA levels:Both>5;pre>5 and post≤5;and both≤5 ng/mL,respectively.We compared the response to CRT based on changes in serum CEA levels.Receiver operating characteristic curve analysis was performed to determine optimal cutoff for neutrophil–lymphocyte ratio and platelet–lymphocyte ratio.Multivariate logistic regression analysis was used to evaluate the prognostic factors for pathologic complete response(pCR)/good response.RESULTS The cohort comprised 145 patients;of them,27,43,and 65 belonged to groups A,B,and C,respectively,according to changes in serum CEA levels before and after CRT.Pre-(P<0.001)and post-CRT(P<0.001)CEA levels and the ratio of downstaging(P=0.013)were higher in Groups B and C than in Group A.The ratio of pathologic tumor regression grade 0/1 significantly differed among the groups(P=0.003).Group C had the highest number of patients showing pCR(P<0.001).Most patients with pCR showed pre-and post-CRT CEA levels<5 ng/mL(P<0.001,P=0.008).Pre-and post-CRT CEA levels were important risk factors for pCR(OR=18.71;95%CI:4.62–129.51,P<0.001)and good response(OR=5.07;95%CI:1.92–14.83,P=0.002),respectively.Pre-CRT neutrophil–lymphocyte ratio and post-CRT T≥3 stage were also prognostic factors for pCR or good response.CONCLUSION Pre-and post-CRT CEA levels,as well as change in CEA levels,were prognostic markers for treatment response to CRT and may facilitate treatment individualization for rectal cancer.

Cytokeratms and carcinoembryonic antigen in diagnosis,staging and prognosis of colorectal adenocarcinoma

AIM: To evaluate the serum levels of cytokeratins and carcinoembryonic antigen (CEA) in diagnosis, staging and prognosis of patients with colorectal adenocarcinoma.METHODS: The sample consisted of 169 patients. One hundred blood donors formed the control group. Radical surgery was performed on 120 patients, with an average follow-up duration of 22.3 mo. Relapses occurred in 23individuals after an average of 18.09 mo. CEA was assayed via the Delfia(R) method with a limit of 5 ng/mL. Cytokeratins were assayed via the LIA-mat(R) TPA-M Prolifigen(R) method with a limit of 72 U/L.RESULTS: In the diagnosis of patients with colorectal adenocarcinoma, CEA showed a sensitivity of 56%, a specificity of 95%, a positive predictive value of 94%, a negative predictive value of 50% and an accuracy of 76.8%.TPA-M had a sensitivity of 70%, a specificity of 96%, a positive predictive value of 97%, a negative predictive value of 66% and an accuracy of 93.6%. The elevation of one of the markers was shown to have a sensitivity of 76.9%, a specificity of 91%, a positive predictive value of 93.5%, a negative predictive value of 70% and an accuracy of 83.6%.There was no variation in the levels of the markers according to the degree of cell differentiation while there was an elevation in their concentrations in accordance with the increase in neoplastic dissemination. There was a statistically significant difference between the patients with stage Ⅳ lesions and those with stages Ⅰ, Ⅱ and Ⅲ tumors.With regard to CEA, the averagelevel was 14.2 ng/mL in patients with stage Ⅰ lesions, 8.5 ng/mL in patients with stage Ⅱ lesions, 8.0 ng/mL in patients with stage Ⅲ lesions and 87.7 ng/mL in patients with stage Ⅳ lesions. In relation to TPA-M, the levels were 153.1 U/L in patients with stage Ⅰtumors, 106.5 U/L in patients with stage Ⅱ tumors, 136.3 U/L in patients with stage Ⅲ tumors and 464.3 U/L in patients with stage Ⅳ tumors. There was a statistical difference in patients with a high CEA level in relation to a shorter survival(P＜0.05). However, there was no correlation between patients with high TPA-M levels and prognostic indices of patients undergoing radical surgery.CONCLUSION: Cytokeratins demonstrate a greater sensitivity than CEA in the diagnosis of colorectal adenocarcinoma.There is an increase in the sensitivity of the markers with tumor dissemination. Cytokeratins cannot identify the worse prognosis in patients undergoing radical surgery.Cytokeratins constitute an advance in the direction of a perfect tumor marker in the treatment of patients with colorectal cancer.

Selection of DNA aptamer that specific binding human carcinoembryonic antigen in vitro

Objective：To select the specific aptamer of carcinoembryonic antigen （CEA）, one of the most attractive molecule for cancer target therapy and imaging. Methods： Seven rounds in vitro selection were performed against the purified CEA protein. Ligand-mediated target purification and Co-immunoprecipitation were adopted to verify the specific binding of the aptamer to the purified and native protein separately. Results：The CEA-specific aptamer which can bind both the purified and native protein with the high specificity was obtained. Conclusion：This is the first time the CEA specific apatmer was produced. The results in this study provides the preliminary evidence for further investigation and application of CEA-aptamer in the future.

Significance of serum carcinoembryonic antigen in metastatic breast cancer patients:A prospective study

BACKGROUND Carcinoembryonic antigen(CEA)is an important serum tumour marker with a substantial role in diagnosis and monitoring of various solid tumours.About 36%-70%of breast cancers have elevated serum CEA.And the available studies show discrepancy in addressing the prognostic significance of CEA in advanced breast cancer.AIM To estimate the serum CEA level in our metastatic breast cancer patients and correlate it with response to treatment and clinical outcome.METHODS This was a prospective clinical study conducted on 50 metastatic breast cancer patients treated at breast clinic,with newly diagnosed metastatic breast cancer planned for palliative chemotherapy,targeted therapy,and hormonal treatment.We estimated the proportion of patients with elevated serum CEA level at baseline and after palliative treatment and also studied the association of serum CEA levels with known prognostic factors.The response to treatment was correlated with the serum CEA levels in the context of responders and nonresponders.RESULTS The median pre-treatment and post-treatment CEA levels were 7.9(1.8-40.7)ng/mL and 4.39(1.4-12.15)ng/mL,respectively,in the whole study population(P=0.032).No statistically significant difference was seen in baseline serum CEA between responders and non-responders.Even in the luminal group,pretreatment serum CEA was not a predictor of response,but post-treatment CEA was a significant predictor of tumour progression.In patients with liver and lung metastases,post-treatment CEA level difference was not statistically significant in both responders and non-responders though the values were higher in nonresponders.Among those with bone metastases,69.5%had elevated post-treatment serum CEA,and only 37.5%had elevated serum CEA in those with no bone metastases.CONCLUSION Elevated post-treatment serum CEA levels are associated with disease progression and poor response to therapy.Persistently elevated post-treatment serum CEA levels are significantly associated with bone metastases.Elevated serum CEA and hormonal status are significant predictors of treatment response.

The potential of carcinoembryonic antigen,p53,Ki-67 and glutathion Stransferase-π as clinico-histopathological markers for colorectal cancer

Objective： Colorectal cancer is one of the major contributors to cancer death worldwide. Lack of reliable colorectal cancer markers has hampered the management of these cancer patients. Our main purpose was to study the correlation between histopathological variables of colorectal adenocarcinomas and identify histopathological markers that are of prognostic value in patients with colorectal cancer. Methods： In the present study, we examined the expression of carcinoembryonic antigen （CEA）, p53, Ki-67 and glutathion Stransferase （GST） -n by using immunohistochemical staining methods in 126 colorectal carcinoma patients and evaluated the lymph node metastasis status in these patients by histopathological examination. Results： The positive rates of CEA, p53, Ki-67 and GST-π expression in the colorectal cancer tissue specimens examined were 95.23%, 55.56%, 53.38% and 82.30%, respectively. Expression of p53 and Ki-67 was significantly correlated with the Dukes stages of the tumor, with higher levels of these proteins in Dukes＇ C and D tumors than those in Dukes＇ A and B tumors. Furthermore, the expression of p53, GST-π and Ki-67 correlated with prognosis of patients with colorectal cancer. Additionally, the expression of p53 in colorectal cancer was closely related to the expression of Ki-67 and the expression of GST-π was directly correlated with that of p53. Conclusion： The expression of CEA, p53, Ki-67 and GST-π was correlated with various clinical features of patients with colorectal cancer. The combined use of these histopathological markers appeared to be a promising tool in predicting the prognosis of patients with this type of cancer.

Construction, Expression and Characterization of a Chimeric Protein Targeting Carcinoembryonic Antigen in Lung Cancer

The carcinoembryonic antigen（CEA） is an oncofetal glycoprotein known as an important clinical tumor marker and is overexpressed in several types of tumors, including colorectal and lung carcinomas. We constructed a chimeric protein that exhibits both specific binding and immune stimulating activities, by fusing staphylococcal enterotoxin A（SEA） to the C-terminus of an anti-CEA single-chain disulfide-stabilized Fv（scdsFv） antibody （single-chain-C-terminus/SEA, SC-C/SEA）. The SC-C/SEA protein was expressed in Escherichia coli（E. coli）, refolded, and purified on an immobilized Ni2＋ affinity chromatography column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis（SDS-PAGE） and Western blot analysis reveal that the target protein was expressed sufficiently. We used immunofluorescence assays to demonstrate that SC-C/SEA could bind specifically to human lung carcinoma cells（A549）, but almost human uterine cervix cells（HeLa）. We also used the L-lactate dehydrogenase（LDH） release assay to show that SC-C/SEA elicits a strong A549 tumor-specific cytotoxic T lymphocyte（CTL） response in vitro. The results suggest that SC-C/SEA shows specific activity against CEA-positive cells and has potential application in CEA-targeted cancer immunotherapy.

CHARACTERIZATION OF MONOCLONAL ANTIBODY CL58 AGAINST CARCINOEMBRYONIC ANTIGEN(CEA)AND STUDY OF ITS BIODISTRIBUTION

Objective: To study the preparation and characterization of monoclonal antibody (McAb) against carcinoembryonic antigen (CEA). Methods: CEA antigen was extracted from metastasized liver of patients with colorectal cancer and used for the preparation of McAb against CEA by hybridoma technique. Immunoreactivity of McAb to CEA antigen was evaluated using ELISA. Mouse ascites was purified by two steps, high performance liquid chromatography (HPLC) using protein A and high performance hydroxylapatite (HPHT). Normal adult tissues and tumor specimen were used for immunohistochemical evaluation of the McAb. Isotope 99mTc labeled CEA McAb was used for biodistribution in tumor-bearing mouse. Results: Purified CEA antigen was a glycoprotein of 180 kD. Anti-CEA McAb affinity constant was 7.4×109/M. The McAb showed positive staining in 54–88% of colorectal cancer, gastric cancer and lung cancer, while negative for normal tissues. 24 hours after injection of 99mTc labeled McAb, tumor ID%/g was higher than 15% and tumor/blood, tumor/kidney and tumor/liver were 1.82, 1.51 and 2.92 respectively. T/NT ratios of other viscera were over 3.0. Conclusion: Purified CEA antigen had very good immunogenicity. The anti-CEA McAb was highly specific. 99mTc labeled McAb was stabled both in vivo and in vitro. In vivo distribution result was satisfactory. McAb CL58 may be useful for RII and RIGS.

Dynamic monitoring of carcinoembryonic antigen,CA19-9 and inflammation-based indices in patients with advanced colorectal cancer undergoing chemotherapy

BACKGROUND The roles of carcinoembryonic antigen(CEA)and carbohydrate antigen(CA19-9)in monitoring the patient response to chemotherapy for metastatic colorectal cancer(mCRC)are not clearly defined,and inflammatory indices,including the neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR)and systemic immune-inflammation index(SII),have been sparsely investigated for this purpose.AIM To aim of this study was to evaluate the relationship between the kinetics of CEA,CA19-9,NLR,LMR,PLR and SII in serum and patient response to chemotherapy estimated by computed tomography(CT)in patients with unresectable mCRC.METHODS Patients with mCRC treated with a 1st-line and 2nd-line chemotherapy underwent at least 3 whole-body spiral CT scans during response monitoring according to the Response Evaluation Criteria in Solid Tumour 1.1(RECIST 1.1),and simultaneous determination of CEA,CA19-9,neutrophil,lymphocyte,platelet and monocyte levels was performed.The kinetics of changes in the tumour markers and inflammatory indices were calculated as the percentage change from baseline or nadir,while receiver operating characteristic curves were drawn to select the thresholds to define patients with progressive or responsive disease with the highest sensitivity(Se)and specificity(Sp).The correlation of tumour marker kinetics with inflammatory index changes and RECIST response was determined by univariate and multivariate logistic regression analysis and the clinical utility index(CUI).RESULTS A total of 102 patients with mCRC treated with chemotherapy were included.Progressive disease(PD),defined as a CEA increase of 25.52%,resulted in an Se of 80.3%,an Sp of 84%,a good CUI negative[CUI(Ve-)]value of 0.75 and a good fraction correct(FC)value of 81.2;at a CEA cut-off of-60.85%with an Se of 100%and an Sp of 35.7%for PD,CT could be avoided in 25.49%of patients.The 21.49%CA19-9 cut-off for PD had an Se of 66.5%,an Sp of 87.4%,an acceptable CUI(Ve-)value of 0.65 and an acceptable FC value of 75.An NLR increase of 11.5%for PD had an Se of 67%and an Sp of 66%;a PLR increase of 5.9%had an Se of 53%and an Sp of 69%;an SII increase above-6.04%had an Se of 72%and an Sp of 63%;and all had acceptable CUI(Ve-)values at 0.55.In the univariate logistic regression analysis,CEA(P<0.001),CA19-9(P<0.05),NLR(P<0.05),PLR(P<0.05)and SII(P<0.05)were important predictors of tumour progression,but in the multivariate logistic regression analysis,CEA was the only independent predictor of PD(P<0.05).CONCLUSION CEA is a useful marker for monitoring the chemotherapy response of patients with unresectable mCRC and could replace a quarter of CT examinations.CA19-9 has poorer diagnostic characteristics than CEA but could be useful in some clinical circumstances,particularly when CEA is not increased.Dynamic changes in the inflammatory indices NLR,PLR and SII could be promising for further investigation as markers of the chemotherapy response.

Transcription Activity of Ectogenic Human Carcinoembryonic Antigen Promoter in Lung Adenocarcinoma Cells A549

The transcription activity of ectogenic human carcinoembryonic antigen （CEA） promoter in lung adenocarcinoma cells A549 was investigated for the further gene-targeting therapy. The reporter gene green fluorescent protein （GFP） driven by CEA promoter and human cytomegalovirus （CMV） promoter were relatively constructed and named plasmid pCEA-EGFP and pCMV-GFP respectively. The intensity of fluorescence was detected by fluorescence microscope and flow cytometry analysis after the pCEA-GFP and pSNAV-GFP plasmids were transfected into A549 cells through liposome respectively. The results showed （4,08±0.63） % of the A549 cells transfected with pCEA-AFP plasmid expressed, significantly lower than that of the A549 cells transfected with pCMV-GFP [（43.27±3.54） %]. It was suggested that ectogenic human CEA promoter in lung adenocarcinoma cells A549 was weakly expressed. The distinct specificity of CEA promoter in CEA high expression cells was regarded as a tool in selective gene therapy, but the transcription activity of ectogenic human CEA promoter was needed to increase in the future.

Fast Electrical Detection of Carcinoembryonic Antigen Based on AlGaN/GaN High Electron Mobility Transistor Aptasensor

As one of the most important tumor-associated antigens of colorectal adenocarcinoma, the carcinoembryonic antigen （CEA） threatens human health seriously ali over the globe. Fast electrical and highly sensitive detection of the CEA with A1GaN/GaN high electron mobility transistor is demonstrated experimentally. To achieve a low detection limit, the Au-gated sensing area of the sensor is functionalized with a CEA aptamer instead of the corresponding antibody. The proposed aptasensor has successfully detected different concentrations （ranging from 50picogram/milliliter （pg/ml） to 50 nanogram/milliliter （ng/ml）） of CEA and achieved a detection limit as low as 50pg/ml at Vas = 0.5 V. The drain-source current shows a c/ear increase of 11.5μA under this bias.

DISTRIBUTION AND ULTRASTRUCTURAL LOCALIZATION OF CARCINOEMBRYONIC ANTIGEN (CEA) IN SIGNET RING CELLS OF GASTRIC CANCER

The distribution and ultrastructural localization of CEA in signet-ring cells of 15 gastric cancer specimens were observed by PAP and immunoelectron microscopic methods. The mechanism of abnormal distribution of CEA in the signet-ring cell and its biological significance are discussed. The results showed that the CEA positive rate in signet-ring cells was 100% with the polarity lost in distribution. Under the light microscope, the CEA stain patterns were of two types: cytoplasmic and membranous types. The former was predominant. Under the electron microscope, most of the CEA was distributed on the cell membrane and cytoplasm. CEA was found in intracellular membranous structure of the cancer cells, especially in protein synthesis and transport organellae (RER, Golgi Complex etc.). The synthesis of CEA in cancer cells increased, yet its elimination was somewhat hampered. The result was that the RER became extended and were full of CEA (+) material. In the free signet-ring cell, there was a small and short contact plane. The tight junction was severed as the cell junction reduced. The antigenic determinant of CEA was glycoprotein. The abnormal distribution of CEA in signet-ring cells might be the morphologic reflection of the glycosylation of surface glycoprotein of tumor cells.

IMMUNOHISTOCHEMICAL STUDY OF CARCINOEMBRYONIC ANTIGEN IN THE TRANSITIONAL MUCOSA ADJACENT TO COLORECTAL CANCER

A combined histopathological, mucin histochemi-cal and immunohistochemical study of the transitional mucosa (TM) adjacent to colorectal cancer is presented. Twenty-six resected specimens were studied by hematoxylin and eosin (HE) and high iron diamine-alcian blue (HID-AB). Carcinoem-bryonic antigen (CEA) was demonstrated by peroxi-dase antiperoxidass (PAP) technique. The appearance of the TM is usually thicker, longer and dilated crypts with increased immature and intermediate cells. Variable amount of sialomucins and decrease sulphomucins content as well as increased CEA content are found in the TM. These changes are not seen in non-transitional zone and normal colorectal mucosa. It is suggested that the mucin changes and expression of CEA in the TM may indicate an early primary premalignant changes and may be one of the reasons for the TM affecting the prognosis of patients with large bowel cancer after radical resection.

Prognostic value of serum carcinoembryonic antigen combined with nutritional status control score in patients with colorectal cancer

Objective To investigate the prognostic value of serum carcinoembryonic antigen(CEA)and controlling nutritional status(CONUT)score in patients with colorectal cancer.Methods We retrospectively studied 261 patients with colorectal cancer in our hospital.The patients were divided into two groups by CONUT=3 and CEA=5 ng/mL,and the effects of CONUT score and CEA level on the prognosis and clinicopathological parameters were statistically analyzed.Results(1)Different CONUT scores were significantly correlated with age,tumor diameter,differentiation type,and T stage(P<0.05).The older the patient was,the larger the tumor diameter,undifferentiated tumor,and T stage were,the higher the CONUT score was.(2)Seventy-five patients died during the follow-up period,and 45 patients died of progression or recurrence of colorectal cancer.The 5-year overall survival(OS)rate of the low CONUT score group was significantly higher than that of the high CONUT score group,and the 5-year OS rate of the low CEA group was significantly higher than that of the high CEA group;the difference was statistically significant(P<0.01).(3)According to the serum CEA level and CONUT score,the 5-year survival rates of CEAlow/CONUTlow,CEAlow/CONUThigh,CEAhigh/CONUTlow,and CEAhigh/CONUThigh were 84.7%,69%,55.3%,and 36.1%respectively,with statistical significance(P<0.01).(4)The Cox multivariate analysis showed that age,CONUT score,CEA combined with CONUT score,lymph node metastasis,and distant metastasis were independent risk factors for the prognosis of colorectal cancer patients.Conclusion:The combination of CEA detection and CONUT score can more accurately judge the prognosis of colorectal cancer patients.

Bioassay of Carcinoembryonic Antigens by Organic Field-effect Transistors Based on D-A Type Conjugated Polymer

Biosensors based on organic field-effect transistors(OFETs)are one of the most promising electronic devices for emerging bioanalytical applications.The selection of organic semiconductors(OSCs)is essential to improve the sensitivity and reliability of this kind of biosensors.Given the good field effect performance and tunable structures of D-A type conjugated polymers,here,we design two D-A type copolymers[P(BDT-co-DPP2T-ThC_(2))and P(BDT-co-DPP2T-Th)],which are applied as the OSC layers.With carcinoembryonic antigen antibody(anti-CEA)adsorbed onto the OSC layers as the recognition sites,OFETs based biosensors for CEA detection are developed.The experimental findings support that the attachment of ester side groups onto the polymer backbone[as for P(BDT-co-DPP2T-ThC_(2))]is favorable for improved solubility and filming properties of the polymer.The introduction of ester side groups affects molecular stacking and enhances intermolecular forces.The resultant devices show high charge mobility and antibody adsorption ability,both of which are critical for sensitive and facile detection of CEA biomarkers.The reliable determination of CEA down to the picomolar level is determined.It is expected that this kind of biosensors fabricated by D-A type conducting polymers will open new avenues toward the early diagnosis,real-time monitoring and treatment of future cancer diseases.

Preoperative prediction of survival in resectable gallbladder cancer by a combined utilization of CA 19-9 and carcinoembryonic antigen

Background Currently,all frequently used staging systems in gallbladder cancer （GBC） are based on postoperative pathological examinations.In patients undergoing curative operation,there is no effective method to predict survival preoperatively.In this study,we explored whether a combined utilization of two tumor biomarkers,namely carbohydrate antigen 19-9 （CA 19-9） and carcinoembryonic antigen （CEA）,could give a preoperative prediction of survival in resectable GBC.Methods Seventy-three patients who underwent radical resection for GBC were included in this study.A retrospective analysis of clinical-pathological data was conducted.Results By multivariate analysis,CA 19-9 elevation （P ＜0.05） and CEA elevation （P ＜0.001） were discovered as two individual factors for postoperative survival.By a combined utilization,patients were divided into three groups：patients with elevation of CEA （group Ⅰ）,patients with elevation of CA 19-9 but without CEA （group Ⅱ）,and patients with nonelevations of either CA 19-9 or CEA （group Ⅲ）.The cumulative 5-year survival rates in groups Ⅰ,Ⅱ,and Ⅲ were 0,14.0％,and 42.8％,respectively （P ＜0.05）.Conclusions By a combined utilization of CA 19-9 and CEA,individualized prediction of survival is available in resectable GBC before operation.Extended radical operation brings the most prognostic benefits in patients with nonelevations of either CA 19-9 or CEA.However,if operation would be in a larger-scale destructive manner,careful consideration of surgical decisions should be made in patients with elevation of tumor biomarkers,especially CEA.

Ultrasensitive electrochemical immunosensor of carcinoembryonic antigen based on gold-label silver-stain signal amplification

A novel gold-label silver-stain electrochemical immunosensor was developed based on polythioninegold nanoparticles（PTh-Au） modified glassy carbon electrode（GCE） as a platform and secondary antibody labeled Au NPs（Ab;-Au） as immumoprobe for carcinoembryonic antigen（CEA） detection. The sandwich-type biosensor adopted anodic stripping voltammetry to detect silver stripping signal when the Ab;-Au of the formed immunocomplexes were stained with silver. The optimized detection conditions were investigated. The effect of different electrochemical responses at various concentrations of CEA was checked by anodic stripping voltammetry. This immunosensor showed a low detection limit of 0.055 ng/mL and a wide linear calibration of 0.1-120 ng/mL（R;=0.99856）. Moreover, this immunoassay also existed the advantages of good reproducibility, stability and selectivity. Thus, this immunosensing protocol may provide a potential application for effective clinical detection of CEA.

HSVTK Gene Therapy for CarcinoembryonicAntigen-Producing Human Lung Cancer Cells

The long-term success of gene therapy for cancer relies heavily on the development of effective targeting systems. We investigate the possibility of targeted gene therapy using promoter of carcinoembryonic antigen (CEA) gene. By using luciferase reporter gene, we found that CEA promoter exhibit 16 times high activity in CEA-producing lung cancer cells, A549 than in nonproducing cells, Hela. We also constructed a recombinant expression plasmid pCEATK, in which CEA promoter drives the effector gene, thymidine kinase gene of Herpes Simplex Virus (HSVTK). A549 cells transfected with pCEATK became 865 times more sensitive to ganciclovir (GCV) than the control cells. However, Hela cells transfected with this plasmid remained resistant to GCV. These data indicate the potential for targeted gene therapy using the CEA promoter against CEA-producing tumor cells, such as lung cancer cells.