Assessment of circulating biomarkers for detection of lung cancer in a high-risk cohort.

BACKGROUND: There is an urgent need for early detection of lung cancer. Screening with low-dose computed tomography (LDCT) is now implemented in the US. Supplementary use of a lung cancer biomarker with high specificity is desirable. OBJECTIVE: To assess the diagnostic properties of a biomarker panel consisting of cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). METHODS: A cohort of 250 high-risk patients was investigated on suspicion of lung cancer. Ahead of diagnostic work-up, blood samples taken. Cross-validated prediction models were computed to assess lung cancer detection properties. RESULTS: In total 32% (79/250) of patients were diagnosed with lung cancer. Area under the curve (AUC) for the three biomarkers was of 0.795, with sensitivity/specificity of 57%/93% and negative predictive value of 83%. When combining the biomarkers with US screening criteria, the AUC was 0.809, while applying only US screening criteria on the cohort, yielded an AUC of 0.62. The ability of the biomarkers to detect stage I-II lung cancer was substantially lower; AUC 0.54. CONCLUSIONS: In a high-risk cohort, the detection properties of the three biomarkers were acceptable compared to current LDCT screening criteria. However, the ability to detect early stage lung cancer was low.

Liver Tumor Markers, HALP Score, and NLR: Simple, Cost-Effective, Easily Accessible Indexes for Predicting Prognosis in ICC Patients after Surgery.

INTRODUCTION: To investigate the prognostic significance of liver tumor markers, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score; neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), for predicting the specific site of recurrence or metastasis after surgery in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: In total, 162 patients with pathologically proven ICC who underwent curative surgery at Sun Yat-sen University Cancer Center between April 2016 and April 2020 were analyzed. Clinicopathological characteristics were collected retrospectively. The Kaplan-Meier method was used to analyze the overall survival (OS) and recurrence-free survival (RFS). Significant clinical factors were examined by univariate analysis and multivariate analysis and analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: The cutoff values for the HALP score, NLR, and PLR were determined to be 43.63, 3.73, and 76.51, respectively, using the surv_cutpoint function of survminer using RFS as the target variable. In multivariate analysis, vascular invasion, pathology nerve tract invasion, and carbohydrate antigen 19-9 (CA19-9) levels were independent prognostic factors of OS, whereas the tumor number, pathology microvascular invasion, pathology differentiation, CA19-9 levels, and NLR were independent prognostic factors of RFS. For the whole recurrence analysis, the carcinoembryonic antigen (CEA) index exhibited the largest ROC curve area of all (AUC = 0.590), and the alpha-fetoprotein (AFP) index exhibited the smallest ROC curve area (AUC = 0.530). The HALP score exhibited the largest ROC curve area of all in predicting intrahepatic recurrence (AUC = 0.588), the NLR showed the best predictive value in predicting lymph node metastasis (AUC = 0.703), and the AUC of the CA19-9 index was the largest of all variables in predicting distant metastasis (AUC = 0.619). CONCLUSIONS: Our study showed that CA19-9, CEA, HALP score, and NLR are easily accessible, reliable, cost-effective indexes for predicting the specific site of recurrence or metastasis after surgery in ICC patients. Patients with high HALP scores and NLR have a higher risk of intrahepatic and lymph node metastasis recurrence.

Prognostic assessment of tumor markers in lung carcinomas

SUMMARY BACKGROUND: Serum tumor markers are molecules that are secreted by tumor cells and may be present in small amounts in the serum of healthy individuals. Their role as prognostic factors in lung cancer remains controversial. OBJECTIVE: To assess the prognostic role of CEA, CA 19-9, CA 15-3, and CA 125 in non-squamous non-small cell lung cancer. PATIENTS AND METHODS: A total of 112 patients with non-squamous non-small cell lung cancer from two Oncology Centers were retrospectively analyzed. Tumor marker levels were measured prior to treatment. Data regarding clinical characteristics and overall survival were collected. RESULTS: Median overall survival of all patients was 15.97 months. Pre-treatment elevations of CA 125 and CA 15-3 were associated with shorter overall survival (p=0.004 and p=0.014, respectively). Single CEA and CA 19-9 elevations were not associated with a worse prognosis. Patients with two or more elevated markers had a statistically significant decrease in overall survival (p=0.008). In the multivariate analysis, smoking status and number of positive tumor markers at diagnosis were independently associated with a worse prognosis. CONCLUSION: High pre-treatment levels of tumor markers were correlated with decreased survival in patients with non-squamous non-small cell lung cancer.

The role of carcinoembryonic antigen as an assessment tool for predicting disease severity among patients with colorectal cancer in resource-poor setting of Kwazulu-Natal, South Africa.

INTRODUCTION: the most reliable screening tool for colorectal cancer, colonoscopy, is not readily accessible in resource-deprived settings of KwaZulu-Natal. The aim of this study was to determine whether serum carcinoembryonic antigen (CEA) levels in patients symptomatic for lower gastrointestinal (GI) pathology correlates with the histological presence and severity of primary colorectal cancer in a large referral centre. Perhaps CEA may have a larger role as a marker for colorectal cancer (CRC) development in these resource deprived communities. METHODS: this study was a retrospective analysis of prospectively collected clinical data of 380 pretreatment patients with colorectal cancer attending a tertiary referral centre in KwaZulu-Natal. Data were analyzed using descriptive statistics and findings were compared with those from the existing literature. RESULTS: the mean CEA level of the study population was 170.0 ± 623.3 µg/l. The number of participants with a CEA level <5 µg/l was 151 (39.74%) whilst the majority 229 (60.26%) had a CEA level ≥ 5 µg/l. There was no significant correlation between CEA levels and gender (p=0.8) or age (p=0.6). CEA levels were highest in the black African race group. Pairwise comparison demonstrated a statistically significant difference between the black and Indian population groups (p=0.02). The current study demonstrates an upregulation of CEA as the stage of CRC progresses (p<0.0001). CONCLUSION: there was no significant difference in CEA levels across age and gender. A positive correlation was noted between CEA level and stage of CRC. Carcinoembryonic antigen levels were highest in the black race group. Low sensitivity of CEA as a screening test for CRC was confirmed.

Methylated PTGER4 is better than CA125, CEA, Cyfra211 and NSE as a therapeutic response assessment marker in stage IV lung cancer.

Real-time assessment of therapeutic response in patients with advanced lung cancer presents a major challenge throughout the treatment process. Currently, computed tomography imaging is often used; however, it is radiation-based and hysteretic and is not suitable for repeated use as a real-time assessment. Blood biomarkers represent a novel solution for assessing therapeutic response in patients with advanced lung cancer. In the present study, the efficacy of a methylation marker [methylated prostaglandin E receptor 4 (mPTGER4)] and four protein markers [carcinoma antigen 125 (CA125), carcinoembryonic antigen (CEA), cytokeratin 19-fragments (cyfra21-1) and neuron-specific enolase (NSE)] were simultaneously evaluated to determine their potential in facilitating therapeutic response monitoring as well as their prognostic values in patients with stage IV lung cancer. The results indicated that, following treatment, the blood levels of methylated PTGER4 and NSE had significantly decreased, and mPRGER4, CA125, CEA and NSE exhibited a significant decrease in percentage level. Since mPTGER4 exhibited a higher rate of positive detection prior to therapy, and a greater response of sensitivity to therapy compared to the protein markers, it may represent an improved marker for the monitoring of therapeutic response. The efficacy of the markers in predicting the overall survival (OS) rate of patients with stage IV lung cancer was also assessed. Results from the follow-up of patients (up to 891 days) revealed that the blood levels of mPTGER4, CA125 and NSE before treatment were able to predict overall survival (OS) rate. Additionally, the percentage change in expression levels of CA125, CEA and NSE was also able to predict the OS rate. In conclusion, the present results indicate that mPTGER4 represents an improved biomarker for monitoring therapeutic efficacy compared with CA125, CEA, Cyfra21-1 and NSE. In predicting the long-term survival of patients with stage IV lung cancer; however, the pre-treatment levels of mPTGER4, CA125 and NSE and the percentage changes of CA125, CEA and NSE may be used as the markers.

Association of Carcinoembryonic Antigen with Mortality in an Insurance Applicant Population.

Objectives.- To quantify the mortality risks associated with elevated levels of carcinoembryonic antigen (CEA). Background.- Carcinoembryonic antigen is cell surface glycoprotein and has been associated with the presence of high grade or metastatic cancers of the colon as well as other malignant and non-malignant disease. Prior publications have demonstrated the utility of CEA levels in the determination of mortality risk in life insurance applicants. The aim of this paper is to further characterize this risk with a larger set of data containing additional person-years of follow-up, more outcomes, and additional variables potentially associated with occult malignancy. Methods.- By use of the Social Security Death Index, mortality was examined in 321,574 insurance applicants age 50 years and older, who submitted blood samples to Clinical Reference Laboratories for testing including CEA. Results were stratified by age group and by CEA level (<5 ng/mL, 5 to 9.9 ng/mL, 10+ ng/mL), though other thresholds were tested. Mortality comparisons were carried out using Cox models and tabular methods with the 2015 smoker-distinct Valuation Basic Tables as a comparator. Results.- Relative mortality is increased at CEA levels above 4.0 ng/mL in both smokers and non-smokers. This association is persistent in Cox models when albumin, BMI and cholesterol are included as covariates. The strongest association with mortality risk occurred in the first 3-4 durations. The 3-year cumulative mortality ratio when using the 2015 VBT as baseline was 6.51 when comparing the group with CEA levels of 10+ ng/mL, compared to those with levels below 5.0 ng/mL. Conclusion.- This study shows that CEA is strongly associated with the risk of early excess mortality in life insurance applicants, and this risk appears not to be mitigated by consideration of other markers thought to be associated with occult malignancy.

The clinical value of carcinoembryonic antigen for tumor metastasis assessment in lung cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) as a diagnostic or prognostic marker has been widely studied in patients with lung cancer. However, the relationship between serum CEA and tumor metastasis in lung cancer remains controversial. This study aimed to investigate the ability of serum CEA to assess tumor metastasis in lung cancer patients. METHODS: We performed a retrospective analysis of 238 patients diagnosed with lung cancer from January to December 2016 at pneumology department of Dazhou Central Hospital (Dazhou, China). Serum CEA levels were quantified in each patient at the time of diagnosis of lung cancer. Metastasis was confirmed by computed tomography (CT), and/or positron emission tomography (PET) and/or surgery or other necessary detecting methods. RESULTS: Of the 213 patients eligible for final analysis, 128 were diagnosed with metastasis and 85 were diagnosed without metastasis. Compared to non-metastatic patients, the serum CEA was markedly higher in patients with metastasis (p < 0.001), and the area under the curve (AUC) was 0.724 (95% CI [0.654-0.793]). Subsequent analyses regarding the number and location of tumor metastases showed that CEA also had clinical value for multiple metastases versus single metastasis (AUC = 0.780, 95% CI [0.699-0.862]) and distant metastasis versus non-distant metastasis (AUC = 0.815, 95% CI [0.733-0.897]). In addition, we found that tumor size, histology diagnosis, age and gender had no impact on the assessment performance of CEA. CONCLUSION: Our study suggested the serum CEA as a valuable marker for tumor metastases assessment in newly diagnosed lung cancer patients, which could have some implications in clinical application.

Potential role of MicroRNA 200c gene expression in assessment of colorectal cancer.

BACKGROUND AND AIM: Colorectal cancer (CRC) is a common cancer worldwide that affects men and women of all racial and ethnic groups. Recent evidence supports the role of microRNAs in CRC. We planned to investigate microRNA200c expression and its relation with diagnosis, prognosis, metastasis and overall survival in CRC patients. This study enrolled 90 subjects (3'0 CRC patients, 30 patients with benign colorectal polyps and 30 healthy control subjects). METHODS: Laboratory investigations included measurement of serum CA19-9 and CEA by enzyme linked immunosorbent assay (ELISA) method and relative quantitation (RQ) of microRNA200c gene expression by real time PCR technique. RESULTS: Significant higher MicroRNA200c expression levels in CRC patients versus both benign (P < 0.011) and control groups (P < 0.001), additionally, benign group had elevated levels versus control (P < 0.001). MicroRNA 200c at cutoff >4.56 had sensitivity 86.67% and specificity 73.33% (P < 0.001) for CRC discrimination. Kaplan-Meier survival analysis revealed significant association (P = 0.028) of high expression of microRNA200c with decreased overall survival. CONCLUSION: Noticeable up-regulation of microRNA200c in CRC and its remarkable relation with unfavorable survival suggesting its potential dual use as a diagnostic and prognostic biomarker for CRC.

Efficient label-free chemiluminescent immunosensor based on dual functional cupric oxide nanorods as peroxidase mimics.

Dual-functional cupric oxide nanorods (CuONRs) as peroxidase mimics are proposed for the development of a flow-through, label-free chemiluminescent (CL) immunosensor. Forming the basis of this cost-efficient, label-free immunoassay, CuONRs, synthesized using a simple hydrothermal method, were deposited onto epoxy-activated standard glass slides, followed by immobilization of biotinylated capture antibodies through a streptavidin bridge. The CuONRs possess excellent catalytic activity, along with high stability as a solid support. Antigens could then be introduced to the sensing system, forming large immunocomplexes that prevent CL substrate access to the surface, thereby reducing the CL signal in a concentration dependent fashion. Using carcinoembryonic antigen (CEA) as a model analyte, the proposed label-free immunosensor was able to rapidly determine CEA with a wide linear range of 0.1-60ngmL-1 and a low detection limit of 0.05ngmL-1. This nanozyme-based immunosensor is simple, sensitive, cost-efficient, and has the potential to be a very promising platform for fast and efficient biosensing applications.

Assessment of Serum Levels of the Adipocytokine Chemerin in Colorectal Cancer Patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. The tumor microenvironment is very important for determining cancer cell growth and spreading. Chemerin, a newly identified adipokine secreted by adipose tissue, is known to be associated with obesity, metabolic syndrome, and insulin resistance. The present study was carried out to investigate the association between serum levels of chemerin and colorectal cancer. METHODS: Thirty-two patients with colorectal cancer aged 57.6±6.5 years, and twenty age, sex and BMI matched healthy controls were included in the study. Serum che me rin levels were determined using enzyme linked immuno sorbent assay. C-reactive protein (CRP) levels were determined using a turbidimetric immunoassay. Carcino embryonic antigen (CEA) and carbohydrate antigen (CA 19-9) were measured by radioimmunoassay. RESULTS: Chemerin levels were found to be significantly higher in patients relative to the controls (P<0.001) and gradually increased with the TNM tumor stage progression. The mean CRP, CEA and CA 19-9 levels were also significantly higher in patients (P<0.001). There was a significant correlation between the serum levels of chemerin and the other measured parameters in CRC patients. The area under receiver operating characteristic curve (ROC) for serum chemerin was 1 at a cut-off value ≥ 161.5 with 100% sensitivity and 100% specificity. CONCLUSIONS: Conclusions: The observed results suggest that chemerin may have a potential role in the pathogenesis and progression of colorectal malignancy and may be a good biomarker of colorectal cancer and stage progression.

Horseradish peroxidase-labeled silver/reduced graphene oxide thin film-modified screen-printed electrode for detection of carcinoembryonic antigen.

In this study, a disposable and simple electrochemical immunosensor was fabricated for the detection of carcinoembryonic antigen. In this method, silver nanoparticles (AgNPs) were mixed with reduced graphene oxide (rGO) to modify the surface of screen-printed carbon electrode (SPE). Initially, AgNPs-rGO modified-SPEs were fabricated by using simple electrochemical deposition method. Then the carcinoembryonic antigen (CEA) was immobilized between the primary antibody and horseradish peroxidase (HRP)-conjugated secondary antibody onto AgNPs-rGO modified-SPEs to fabricate a sandwich-type electrochemical immunosensor. The proposed method could detect the CEA with a linear range of 0.05-0.50µgmL-1 and a detection limit down to 0.035µgmL-1 as compared to its non-sandwich counterpart, which yielded a linear range of 0.05-0.40µgmL-1, with a detection limit of 0.042µgmL-1. The immunosensor showed good performance in the detection of carcinoembryonic antigen, exhibiting a simple, rapid and low-cost. The immunosensor showed a higher sensitivity than an enzymeless sensor.

Dynamic assessment of carcinoembryonic antigen in the first month after liver resection for colorectal liver metastases as a rapid-recurrence predictor.

BACKGROUND: Carcinoembryonic antigen (CEA) is a tumor marker used widely for detecting the recurrence and predicting the prognosis of colorectal cancer. This study investigates the possibility of serial measurement of serum CEA in several weeks after liver resection for colorectal liver metastases (CRLM) in detecting earlier detection of recurrence. METHODS: From 2007 to 2014, CEA levels were assessed at 1 week and at 2-3 weeks after curative-intent liver resection among a total of 240 patients with CRLM. The CEA half-life was calculated and patients were divided into two groups: those with a CEA half-life ≤10 days or normalized (Group S), and those with a CEA half-life >10 days or rising (Group L). RESULTS: The 1-, 3-, and 5-year overall survival rates in Group S versus Group L were 91.3% versus 83.3%, 64.0% versus 41.3%, and 44.2% versus 29.3%, respectively (P = 0.0079). Multivariate analysis revealed that resection of extrahepatic lesions, four or more lesions of liver metastases, and categorization in Group L were independent factors of rapid recurrence within 100 days. CONCLUSION: A CEA half-life >10 days or rising 1 month after curative-intent liver resection was associated with rapid recurrence of CRLM within 100 days. J. Surg. Oncol. 2016;113:463-468. © 2016 Wiley Periodicals, Inc.

[Diagnostic capability of carcinoembryonic antigen elevation]. / Capacidad diagnóstica del antígeno carcinoembrionario.

INTRODUCTION: There is little information on the oncologic diagnostic accuracy of carcinoembryonic antigen (CEA) levels more than 3-fold above normal. OBJETIVES: To determine the prevalence of underlying cancer in patients with mild CEA elevation and the mean cost per patient of CEA determination. METHODS: A retrospective study was carried out in all patients with CEA elevation (3-10 ng/ml) and suspicion of cancer referred to the gastroenterology or internal medicine outpatient units from 2001 to 2007. RESULTS: We studied 100 patients (60 men and 40 women), with a mean age of 67.4 ± 14.2 years and baseline CEA of 5.8 ± 1.7 ng/ml. The most important symptoms and signs were laboratory abnormalities (19 patients [19%]). Cancer was diagnosed in 4 patients (one gastric, 2 lung and one colon). Among patients without malignancies, 49 patients (49%) had no related processes, and 47 (47%) had benign diseases. During follow-up, one laryngeal cancer, one acute myeloid leukemia, and one colon cancer were detected (54.3 ± 24.6 months). We found no differences between baseline CEA levels in patients with and without cancer (6.6 ± 2.4 vs. 5.8 ± 1.7 ng/ml, p = 0.2). The mean cost per patient was 503.6 ± 257.6 €. CONCLUSIONS: Cancer was detected in a small proportion (7%) of patients with mild CEA elevation. The study of these patients is directly and indirectly associated with a not inconsiderable cost.

Assessment of the value of carcinoembryonic antigen reduction ratio as a prognosis factor in rectal cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. This study aimed to investigate the role of CEA reduction ratio after preoperative chemoradiotherapy (CRT). METHODS: We enrolled 284 patients who underwent preoperative CRT followed by radical surgical resection. Patients were divided into 3 groups: serum CEA levels before CRT (pre-CRT CEA) less than 5 ng/mL (group 1); pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio of 50% or more (group 2); and pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio less than 50% (group 3). RESULTS: The 5-year disease-free survival (DFS) rate was not different between groups 1 (71.8%) and 2 (69.4%) but was significantly lower in group 3 (49.5%). CEA group, lymph node status after CRT (ypN) stage, and histologic type were independent prognostic factors for DFS on multivariate analysis. CONCLUSIONS: CEA reduction ratio might be an independent prognostic factor for DFS in rectal cancer patients treated with preoperative CRT and radical surgery.

Combining multiple serum biomarkers in tumor diagnosis: A clinical assessment.

The present study aimed to assess the diagnostic/prognostic value of various clinical tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 (CYFRA21-1), α-fetoprotein (AFP), carbohydrate antigen-125 (CA-125), carbohydrate antigen-19.9 (CA-19.9) and ferritin, individually or in combination. The electro-chemiluminescence immunization method was performed to detect the levels of seven tumor markers in 560 cancer patients and 103 healthy subjects for comparison. The serum levels of the seven markers measured in cancer patients were higher compared to healthy subjects (P<0.05 for AFP and P<0.001 for the remaining six markers). Different markers had different sensitivity towards different types of tumors. Combining more markers significantly increased the ratios of positive diagnosis in the tumors. The diagnostic sensitivities of combining seven markers were particularly high in digestive, urinary and skeletal tumors (82, 92 and 83%, respectively). Gynecological tumors have exhibited a constant yet relatively low positive diagnosis irrespective of the use of a single marker or combined markers. However, the increase in sensitivity when combining markers was accompanied by a decrease in specificity. Generally, combining more markers increased the tumor detection rates, while a combination of the seven markers provided the highest detection rate. Combined detection showed a particularly high sensitivity in detecting respiratory, digestive and urinary system tumors, with the lowest sensitivity observed in gynecological tumors. As a result, combining tumor markers may play an important role in early tumor detection/diagnosis while the loss of specificity can be tolerated.