A novel genotyping method for rapid identification of the Le gene to select patients for diagnosis with CA19-9.

BACKGROUND: The antigenic determinant of CA19-9 is synthesized by the α1,3/4fucosyltransferase encoded by the Le gene in the Lewis blood group system. Accordingly, a diagnosis with CA19-9 is not appropriate forLe-negative patients who possess the Le gene-mutated le alleles homozygously. METHODS: A Le gene-specific PCR was undertaken to determine c59T>G by using a set of tag-sense and biotin-labeled anti-sense primers and a peptide nucleic acid-le-clamp which bound to G59 in the le alleles. Following mixing with streptavidin-coatedbluelatex beads, the PCR products were developed on a strip on which the complementary tag oligonucleotide to theLe gene-specific amplicon was immobilized. RESULTS: When the PCR products were developed on the strip, a clear line was rapidly observed in Le-positive but not in Le-negative individuals. In contrast, a significant number of cancer patients with Lewis-negative phenotype were found to possess CA19-9, while they were specifically genotyped asLe/-. No contradictory results were observed in cancer patients (n = 315) with respect to their Lewis genotypes and CA19-9 levels. CONCLUSIONS: c59T>G occurred commonly in the le alleles could be specifically and rapidly identified by the present method. This method appeared to be relevant forselecting cancer patientsto bediagnosed with CA19-9.

Specific Norovirus Interaction with Lewis x and Lewis a on Human Intestinal Inflammatory Mucosa during Refractory Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is related to immunological and microbial factors, with the possible implication of enteric viruses. We characterized the interaction between human noroviruses (HuNoVs) and blood group antigens in refractory CD and UC using HuNoV virus-like particles (VLPs) and histological tissues. Immunohistochemistry was conducted on inflammatory tissue samples from the small intestine, colon, and rectum in 15 CD and 9 UC patients. Analysis of the regenerative mucosa of the colon and rectum revealed strong expression of sialylated Lewis a (sLea) and Lewis x (sLex) antigens and HuNoV VLP binding in the absence of ABO antigen expression in both UC and CD. Competition experiments using sialidase, lectins, and monoclonal antibodies demonstrated that HuNoV attachment mostly involved Lea and, to a lesser extent, Lex moieties on regenerative mucosa in both UC and CD. Further studies will be required to understand the implications of specific HuNoV binding to regenerative mucosa in refractory IBD.IMPORTANCE Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are progressive diseases affecting millions of people each year. Flare-ups during IBD result in severe mucosal alterations of the small intestine (in CD) and in the colon and rectum (in CD and UC). Immunohistochemical analysis of CD and UC samples showed strong expression of known tumoral markers sialyl Lewis a (CA19.9) and sialyl Lewis x (CD15s) antigens on colonic and rectal regenerative mucosa, concurrent with strong human norovirus (HuNov) VLP GII.4 affinity. Sialidase treatment and competition experiments using histo-blood group antigen (HBGA)-specific monoclonal antibodies and lectins clearly demonstrated the implication of the Lewis a moiety and, to a lesser extent, the Lewis x moiety in HuNov recognition in regenerative mucosa of CD and UC tissues. Further studies are required to explore the possible implications of enteric viruses in the impairment of epithelial repair and dysregulation of inflammatory pathways during severe IBD.

Serum CA 19-9 and CA 125 as a diagnostic marker in carcinoma of gallbladder.

BACKGROUND: Gall bladder carcinoma is endemic in North India along the Ganges belt. Most of the cases usually present in late stage when prognosis is poor. That mandates a necessity for proper screening in these areas for gall bladder lesions. Tumor markers CA 19-9 and CA 125 have been studied in various GI cancers and may also help in the screening, diagnosis and evaluation of gall bladder carcinoma. Aims: To assess serum CA19-9 and serum CA125 in patients with gall bladder lesions and find out a cut off value for diagnosis of carcinoma gallbladder. METHODS AND MATERIAL: Study included 118 cases, with female: male ratio of 4:1.Out of it, 91 (77 %) cases were benign and 27 (23 %) were malignant. Patients' sera was collected and analyzed for CA19-9 and CA 125 by CMIA method. RESULTS: The Mean (SD) value of CA19-9 for benign and malignant cases was found to be 12.86 (17.54) and 625.35(186.52) U/ml. For CA 125 it was found to be 17.98(13.69) and 239.63(73.72) U/ml respectively. The difference was statistically significant (P< 0.001). When Mean - 2SD value of malignant lesions were taken as cut off a value of CA 19-9 and CA 125 were found be 252.31 U/ml & 92.19U/ml respectively, found to be significant to suggest /diagnose a case of carcinoma gall bladder along with clinicoradiological findings. Taking these value as cut off Sensitivity & Specificity for CA 19-9 and CA 125 in detecting malignant cases were found to be 100% & 98.90% and 100% & 94.50% respectively. CONCLUSIONS: It is concluded that both serum CA 19-9 and serum CA 125 may act as a good adjunct for diagnosis of cases of carcinoma gallbladder along with imaging studies. However, changes in CA19-9 are more significant than CA 125.

Inflammation, Tumoral Markers and Interleukin-17, -10, and -6 Profiles in Pancreatic Adenocarcinoma and Chronic Pancreatitis.

BACKGROUND: Interleukin profiles can be used as biochemical markers regarding the early diagnosis of pancreatic cancer. AIMS: To assess CRP, CA 19-9, CEA levels, and interleukin-6, -10, and -17 profiles in pancreatic ductal adenocarcinoma, chronic pancreatitis was compared with a control group, and the correlation with pancreatic cancer survival. METHODS: A total of 87 patients were prospective divided in pancreatic cancer (n = 53), chronic pancreatitis (n = 22) ,and control group (n = 12). The diagnosis of PDAC was made histologically. The diagnosis of chronic pancreatitis was based on medical history, imaging methods, and endoscopic ultrasound. Systemic concentrations of interleukins were measured using ELISA kits. The patients were followed at 1, 3, and 6 months. RESULTS: CRP, CA 19-9, and CEA were higher in the pancreatic cancer group (p < 0.001). Interleukin-10 was significantly higher in the pancreatic cancer and chronic pancreatitis groups (p < 0.001). Interleukin-17 was statistically higher in the pancreatic cancer group (p < 0.0001). The cut-off of interleukin-17 of 0.273 had a sensitivity of 90.9 and a specificity of 80.9 with a curve under ROC of 0.80 in order to differentiate between pancreatic cancer and chronic pancreatitis. The serum levels of interleukins are not correlated with the stage of the disease. CRP, CA 19-9, CEA, and interleukin-6, -10, and -17 were lower in patients with survival more than 6 months. CONCLUSIONS: We detected high levels of interleukin-6, -10, and -17 in chronic pancreatitis and pancreatic cancer. Serum interleukin-17 levels can discriminate between pancreatic cancer and chronic pancreatitis. The prognostic role of interleukins needs to be established.

Functional and genetic characterization of three cell lines derived from a single tumor of an Opisthorchis viverrini-associated cholangiocarcinoma patient.

Three cholangiocarcinoma (CCA) cell line-formerly named, M156, M213 and M214 have been intensively used with discrepancy of their tumor origins. They were assumed to be originated from three different donors without authentication. To verify the origins of these cell lines, the short tandem repeat (STR) analysis of the currently used cell lines, the cell stocks from the establisher and the primary tumor of a CCA patient were performed. Their phenotypic and genotypic originality were compared. The currently used 3 CCA cell lines exhibited similar STR as CCA patient ID-M213 indicating the same origin of these cells. The cell stocks from the establisher, however, revealed the same STR of M213 and M214 cells, but not M156. The misidentification of M214 and M156 is probably due to the mislabeling and cross-contamination of M213 cells during culture. These currently used cell lines were renamed as KKU-213A, -213B and -213C, for the formerly M213, M214 and M156 cells, respectively. These cell lines were established from a male with an intrahepatic mass-forming CCA stage-4B. The tumor was an adenosquamous carcinoma with the liver fluke ova granuloma in evidence. All cell lines had positive CK19 with differential CA19-9 expression. They exhibited aneuploidy karyotypes, distinct cell morphology, cell growth, cytogenetic characteristic and progressive phenotypes. KKU-213C formed a adenosquamous carcinoma, whereas KKU-213A and KKU-213B formed poorly- and well-differentiated squamous cell carcinomas in xenografted mice. mRNA microarray revealed different expression profiles among these three cell lines. The three cell lines have unique characteristics and may resemble the heterogeneity of tumor origin.

Clinical significance of CA 19.9 and LINC01197 in pancreatic cancer.

OBJECTIVE: This study aimed to explore the expression and clinical significance of LINC01197 in serum of patients with pancreatic cancer (PC). PATIENTS AND METHODS: Fifty PC patients (patient group) treated in our hospital from March 2012 to April 2014 were collected, and another 50 normal people (normal group) were collected for physical examination. The LINC01197 expression in serum of the two groups was detected by qRT-PCR method, and the CA 19.9 expression in serum was detected by Roche automatic biochemistry. The expression and diagnostic value of CA 19.9 and LINC01197 in PC were analyzed, and the relationship between LINC01197 and prognosis of PC patients was observed. RESULTS: The CA 19.9 expression in the patient group was significantly higher than that in the normal group (p<0.001). Their area under the curve was 0.791 and 0.944 respectively. The incidence of phases III+IV, lymphatic invasion, and distant metastasis in patients with low expression of LINC01197 is significantly higher than that in those with high expression, and has higher diagnostic value. With the progress of clinical staging, the TNM expression decreased gradually and there were differences between groups (p<0.001). Spearman's test analysis found that the decreased TNM staging of LINC01197 increased gradually (r=-0.816, p<0.001), and the area under the curve of LINC01197 distinguishing phase I and phase II+phase+III+phase IV was 0.930. The 1-year survival rate and 5-year survival rate of patients in low expression group were lower than those in high expression group (p1 year =0.037, p5 year =0.014). Distant metastasis is an independent prognostic factor for PC patients to survive for 1 to 5 years. Differentiation, TNM staging, and LINC01197 are independent prognostic factors for PC patients to survive for 5 years. CONCLUSIONS: The low expression of LINC01197 in PC patients indicates poor prognosis of patients and is expected to be a potential diagnostic and prognostic indicator of PC.

The reference intervals for CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1.

Tumor markers are noninvasive diagnostic tools for cancer. Their abnormal expression often occurs earlier than clinical symptoms or other detection signals. Appropriate reference intervals (RIs) of tumor markers are important for health evaluation, cancer diagnosis, therapy monitoring and prognosis assessment. In this study, we aimed to establish the RIs of cancer antigen 125 (CA125), CA15-3, CA19-9, CA72-4, alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), neuron-specific enolase (NSE) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in apparently healthy Henan population. A total of 1705 apparently healthy participants (21-89 years) were recruited from five representative geographical regions in Henan province. Nonparametric 95th percentile intervals were used to define the RIs of CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1. The test results of CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1 can traceable to reference measurement procedures. The age- and gender-specific RIs of the tumor markers were established. We established age- and gender-specific RIs for CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1. The newly established RIs should be more suitable for Henan population. It will be valuable for clinicians to make a medical diagnosis, therapeutic management decision and other physiological assessment.

Surgical Margin Status of Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Radical Intent: Risk Factors for the Survival Impact of Positive Margins.

BACKGROUND: For pancreatic ductal adenocarcinoma (PDAC), surgical margin status is an important pathological factor for evaluating surgical adequacy. In this study, we attempted to investigate predictive factors for the survival impact of positive surgical margins. MATERIALS AND METHODS: From February 2004 to December 2013, 204 patients were diagnosed with PDAC and underwent surgery with radical intent; 189 patients fulfilled our selection criteria and were enrolled for analysis. RESULTS: For the 189 enrolled patients with PDAC, we found male predominance (112/189, 59%) and a median age of 64 years; most patients were diagnosed with stage IIB disease (n=115, 61%). The positive surgical margin rate was 21% (n=40). Carbohydrate antigen 19-9 (CA19-9) level higher than 246 U/ml (odds ratio (OR)=2.318; 95% confidence interval (CI)=1.037-5.181 p=0.040) and lesion location in the uncinate process (OR=2.996; 95% CI=1.232-7.284 p=0.015) were the only two independent risk factors for positive surgical margins. Positive retroperitoneal soft-tissue margins were the most frequently observed (24/40, 60%). Overall, positive surgical margins had no survival impact in the 189 patients with PDAC who underwent surgery; however, positive surgical margins had an unfavorable survival impact on patients with stage IIA PDAC who underwent surgery. CONCLUSION: Retroperitoneal soft-tissue was the most common site for positive surgical margins. Additionally, surgical margin positivity was more likely for tumors located in the uncinate process than for other tumors. Positive surgical margins had an unfavorable survival impact on patients with stage IIA PDAC who underwent surgery.

Dilemma of elevated CA 19-9 in biliary pathology.

Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker which has been extensively evaluated and widely utilized primarily in diagnosing and prognosticating pancreaticobiliary malignancies. Levels may be significantly influenced and elevated in cases of benign biliary conditions however, especially in obstructive jaundice, thereby posing difficulty in distinguishing between benign and malignant cholestasis. A myriad of studies have focused on elucidating proper use and interpretation of CA 19-9 in pancreatic cancer as well as in the setting of cholestasis. These studies have demonstrated that many factors influence CA 19-9 values and various methods for interpreting CA 19-9 in obstructive jaundice have been proposed. With improvements in diagnostic imaging, advancements in endoscopic modalities, and likelihood that management will not change based on the results of the test, clinicians should be cautious when ordering CA 19-9 and consider the reasons for measuring the tumor marker.

Serum CNPY2 isoform 2 represents a novel biomarker for early detection of colorectal cancer.

Since early diagnosis is very important for treating CRC, we decided to detect peripheral serum canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform 2 to verify its diagnostic value for CRC patients. Serum samples were collected from 430 CRC patients and 201 healthy controls. Enzyme-linked immunosorbent assay (ELISA) detection kits for CNPY2 isoform 2 were generated and then applied to measure serum CNPY2 isoform 2 concentrations. Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were also measured. The median serum CNPY2 isoform 2 concentrations in all CRC patients were significantly higher than those in the healthy control group (all P<0.001). Those with stage I CRC presented the highest area under the receiver operating characteristic curve (AUC) for CNPY2 isoform 2 [0.707, 95% confidence interval (CI): 0.649-0.765, P<0.001]. The diagnostic efficiency of the combination of CNPY2 isoform 2, CEA and CA19-9 was significantly higher than that of each biomarker detected separately (all P<0.0167). Serum CNPY2 isoform 2 may be a valuable biomarker for the early detection of CRC and presents an improvement in the diagnostic efficiency by combination of CEA and CA19-9.

New observations on the utility of CA19-9 as a biomarker in Lewis negative patients with pancreatic cancer.

BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is the best-validated biomarker for pancreatic cancer. The National Comprehensive Cancer Network (NCCN) guideline asserts that "CA19-9 will be undetectable in Lewis antigen-negative individuals". However, reports of CA19-9 secretion and its significance in Lewis (-) patients with pancreatic cancer have been inconsistent. This study was to examine serum CA19-9 levels in patients with pancreatic cancer according to Lewis status. METHODS: Patients with pancreatic cancer (1482 cases) were retrieved from a prospectively maintained database. Patients with benign pancreatic disease (210 cases) and normal subjects (315 cases) were used as controls. Lewis genotypes were examined by fucosyltransferase 3 (FUT3) sequencing. RESULTS: In patients with pancreatic cancer, 8.4% of subjects were Lewis (-), but only 41.9% of Lewis (-) subjects had CA19-9 values ≤ 2 U/mL. CA19-9 was even elevated (>37 U/mL) in 27.4% of Lewis (-) patients. The area under the receiver operating characteristic (ROC) curve for CA19-9 as a diagnostic biomarker was 0.842 in Lewis (-) patients with pancreatic cancer, which is closing to that of CA19-9 applied in all of patients with pancreatic cancer (0.898). Lewis (-) status was an independent prognostic factor for shorter survival in a multivariable analysis (hazard ratio (HR), 1.30, 95% confidence interval (CI), 1.03-1.64; P = 0.028). CONCLUSIONS: Not all Lewis (-) patients with pancreatic cancer are non-secretors of CA19-9. Contrary to general understanding, CA19-9 can retain its utility as a biomarker in these patients in spite of Lewis (-) genotype.

Sulfatase 1 expression in pancreatic cancer and its correlation with clinicopathological features and postoperative prognosis.

BACKGROUND: Recent studies have shown that Sulfatase 1 (SULF1) plays a crucial role in the genesis, development, and progression of tumors. However, there have been few studies on the role of SULF1 in pancreatic cancer. OBJECTIVE: The present study examined the differences in SULF1 expression levels between pancreatic cancer and normal tissues, and their correlation with the clinicopathological features and prognosis. METHODS: A total of 65 pancreatic cancer samples were enrolled in this study. An immunohistochemical assay were used in this study. The relationship between SULF1 expression and clinicopathological features were tested using χ2 test or Fisher's exact test. The Kaplan-Meier method was used to calculate the cumulative survival rates of the patients. RESULTS: The study showed that the SULF1 expression level was higher in pancreatic cancer tissues than in normal tissues. Analysis of the clinical and pathological data of patients revealed that high SULF1 expression was associated with later T, N, and TNM stages, higher CA19-9 levels, smaller tumor size, and poorer prognosis. CONCLUSIONS: These findings suggested that SULF1 could be an indicator of the clinicopathological features and prognosis of pancreatic cancer.

Design, expression and evaluation of novel chimeric protein constructed from colorectal tumor-associated antigen.

There were 134,000 new diagnosis and 49,000 deaths in 2016 due to colorectal cancer. Similar to most cancers, early diagnosis increases the chance of successful treatment. Detection of tumor-associated antigens or the immune response against such markers is one of the most common methods of diagnosis. In that regard, we aimed to design and express a chimeric protein from the most common tumor-associated antigens in colorectal cancer and assess its ability to detect the immune response in comparison with the parental tumor-associated antigens in patient's sera. Through bioinformatics approaches a chimeric protein from carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA19-9) was designed and expressed in E. coli (BL21DE3). Proper folding, expression levels and immune reactivity were assessed by western blot, ELISA and immunohistochemistry. Recombinant proteins functionality and immune reactivity were confirmed by ELISA and Western blot. Results showed that recombinant CEA, recombinant CA19.9 and chimeric protein of CEA- CA19.9 have strong reactivity with antibodies in the sera of colorectal cancer patients, whereas no reactivity was seen with the sera of healthy volunteers. Significantly stronger immune reactivity was seen with the chimeric protein than each of the CEA or CA19.9 alone. Overall, it was concluded that the designed recombinant proteins in this study could be used to detect autoantibodies produced against the colorectal tumor-associated antigens. The chimeric CEA-CA19.9 protein shows a stronger reactivity with the sera antibodies of colorectal cancer patients that CEA or CA19.9 alone.

Glycoprotein CA19.9-specific monoclonal antibodies recognize sialic acid-independent glycotope.

A repertoire of monoclonal antibodies was generated by immunization of mice with cancer-associated glycoprotein CA19.9, and two of them were selected as optimal capture and detecting counterparts for sandwich test system for detection of CA19.9. Fine epitope specificity of the antibodies was determined using printed glycan array, enzyme-linked immunosorbent assay, and inhibitory enzyme-linked immunosorbent assay. Unexpectedly, both immunoglobulins did not bind key epitope of CA19.9 glycoprotein, tetrasaccharide SiaLeA, as well as its defucosylated form sialyl LeC (known as CA-50 epitope). The antibodies were found to have different glycan-binding profiles; however, they recognized similar glycotopes with common motif Galß1-3GlcNAcß (LeC), thus resembling specificity of human natural cancer-associated anti-LeC antibodies. We propose that cancer-specific glycopeptide epitope includes Galß1-3GlcNAcß fragment of a glycoprotein O-chain in combination with proximal hydrophobic amino acid(s) of the polypeptide chain.

Current and future biomarkers for pancreatic adenocarcinoma.

Although pancreatic cancer is only the twelfth most common type of cancer in the world, it features a very unfavorable prognosis. The mortality rate almost equals the incidence rate, corroborating the very poor prognosis of pancreatic cancer. The 5-year survival rate for all stages of pancreatic ductal adenocarcinoma is only 7%. Surgical resection represents the only potentially curative treatment option for pancreatic ductal adenocarcinoma patients but is often not feasible due to the advanced stage of the disease upon diagnosis. For advanced disease, palliative chemotherapy is the treatment of choice although the regimens available to date are untargeted and have extensive side-effect profiles, making them unsuitable for patients with a low performance status. For this reason, early detection of pancreatic cancer is essential in order to provide patients with an optimal therapeutic approach. Up to the present day, carbohydrate antigen 19-9 is the only diagnostic marker approved by the U.S. Food and Drug Administration but its diagnostic potential is limited due to its restricted sensitivity and specificity, supporting the urgent need for novel biomarkers. In addition, prognostic and treatment-predictive biomarkers might provide essential information regarding personalized treatment decisions for individual patients. In this article, we aim to review current and future diagnostic, prognostic, and treatment-predictive biomarkers for pancreatic cancer.

Short-term clinical efficacy of percutaneous irreversible electroporation combined with allogeneic natural killer cell for treating metastatic pancreatic cancer.

This study was to determine how the short-term clinical efficacy of irreversible electroporation (IRE) combined with allogeneic natural killer (NK) cell therapy for treating metastatic pancreatic cancer. Between March and December 2016, we enrolled 40 patients who met the enrollment criteria and assigned them to two groups: simple IRE (IRE group, n=20) and IRE plus allogeneic NK cell therapy (IRE-NK, n=20). We evaluated immune function changes, quality of life, clinical response, and other related indicators. Combining allogeneic NK cells with IRE had a synergistic effect, not only enhancing the immune function of the patients, but also reducing the expression of carbohydrate antigen 19-9 (CA19-9) and CA242 and significantly exhibiting good short-term outcome and improving the quality of life of the patients. This is the first clinical trial to combine allogeneic NK cells with IRE for treating metastatic pancreatic cancer, and proves the safety and efficacy of the treatment.

Potential Biomarkers in Lewis Negative Patients With Pancreatic Cancer.

OBJECTIVE: To examine potential biomarkers in Lewis negative patients with pancreatic cancer. BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is currently the most important and widely used biomarker in pancreatic cancer. However, approximately 5 to 10% of the population are Lewis negative individuals, and they are documented to have scarce or no CA19-9 secretion. Therefore, it is necessary to explore potential biomarkers to compensate for this drawback. METHODS: Lewis genotypes were determined in a large cohort of patients with pancreatic cancer (682 cases) and controls (525 cases) by sequencing the Fucosyltransferase 3 (FUT3) gene from genomic DNA. Potential biomarkers were examined in patients with Lewis negative genotypes and normal subjects. The impact of potential biomarkers on tumor burden and survival was analyzed. RESULTS: Forty-seven (6.9%) patients with pancreatic cancer had Lewis negative genotypes. Carcinoembryonic antigen (CEA) and CA125 had greater sensitivity than other biomarkers in Lewis negative patients with pancreatic cancer [CEA, 63.8%; CA125, 51.1%; CA72-4, 25.5%; CA15-3, 21.3%; CA19-9, 19.1%; CA50, 12.8%; CA242, 10.6%; and alpha-fetoprotein (AFP), 0.0%]. In addition, both CEA (98.0%) and CA125 (93.8%) showed a high specificity. Compared with other biomarkers, CEA (60.9%) was sensitive for stage I, II diseases and CA125 (75.0%) was sensitive for stage III, IV diseases. CEA and CA125 were associated with tumor metastasis and therapeutic response. CONCLUSIONS: CEA and CA125 have the potential to be applied as biomarkers in Lewis negative patients with pancreatic cancer. CEA and CA125 should be routinely measured for all patients with pancreatic cancer.

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer.

Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.

Identification of Circulating MiR-25 as a Potential Biomarker for Pancreatic Cancer Diagnosis.

BACKGROUND: The aim of this study was to identify novel microRNAs for potential use in the diagnosis of pancreatic cancer (PaC). METHODS: A total of 1063 serum samples from 303 patients with PaC were collected, and the expression level of miR-25 was measured using quantitative real-time PCR (qRT-PCR). RESULTS: We found that miR-25 had significant diagnostic value for the differential diagnosis of PaC in normal controls with an AUC (the area under the ROC curve) of 0.915 (95% CI: 0.893-0.937) that was significantly higher compared with an AUC of 0.725 for serum tumor marker carcinoembryonic antigen (CEA) and an AUC of 0.844 for CA19-9. CONCLUSIONS: These data suggest that serum miR-25 has strong potential as a novel biomarker for the early detection of PaC.

Standardization of tumor markers - priorities identified through external quality assessment.

Tumor markers are often heterogeneous substances that may be present in elevated concentrations in the serum of cancer patients. Typically measured by immunoassay, they contribute to clinical management, particularly in screening, case-finding, prognostic assessment, and post-treatment monitoring. Data both from external quality assessment (EQA) schemes and clinical studies demonstrate significant variation in tumor marker results obtained for the same specimen using different methods. Between-method between-laboratory coefficients of variation (CV) reported by EQA schemes generally reflect the complexity of the measurand, ranging from <5% for the structurally relatively simple α-fetoprotein (AFP) to >25% for the complex mucinous cancer antigen 19-9 (CA19-9). Improving the standardization of tumor marker measurements is particularly important for three reasons. The primary use of tumor markers is in monitoring cancer patients over long periods of time. Clinical interpretation of trends may consequently be affected if results are obtained in different laboratories using different methods or if a laboratory has to change method. Differences in results may have major implications for adoption of area-wide decision cut-offs and make implementation of these difficult. Method-related differences also make it difficult to compare clinical studies. Improving comparability of tumor marker results requires broad international agreement about which molecular forms of the measurand have clinical utility, identifying and adopting pure molecular forms as calibrants, and defining antibody specificities for their optimal detection. These aims have been achieved to varying extents for the most frequently measured serum tumor markers as described in this paper.