Serum tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4, carbohydrate antigen 24-2, ferritin) and gastric cancer prognosis correlation

BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common tumors worldwide. The survival rate after the onset of symptoms is generally less than one year for the late presentation of HCC, and reliable tools for early diagnosis are lacking. Therefore, novel biomarkers for the early detection of HCC are urgently required. Recent studies show that the abnormal release of proteins by tumor cells can elicit humoral immune responses to self-antigens called tumor-associated antigens(TAAs). The corresponding autoantibodies can be detected before the clinical diagnosis of cancer. Therefore, there is growing interest in using serum autoantibodies as cancer biomarkers. In this review, we focus on the advances in research on autoantibodies against TAAs as serum biomarker for detection of HCC, the mechanism of the production of TAAs, and the association of autoantibodies with patients' clinical characteristics.

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.

Carbohydrate Antigens as Potential Biomarkers for the Malignancy in Patients with Idiopathic Deep Venous Thrombosis:A Retrospective Cohort Study

A variety of biomarkers have been identified in recent prospective and retrospective re- ports as being potentially predictive of venous thromboembolis （VTE）, particularly idiopathic deep venous thrombosis （IDVT）. This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients （54 females and 74 males; average age： 50.9＋17.4 years） were included. Carcinoembryonic antigen （CEA）, ferritin, β2-microglobulin, cancer antigen （CA） 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen （SCC）, alpha-fetoprotein （AFP）, prostate specific antigen （PSA）, free PSA （f-PSA）, and beta-human chorionic gonadotropin （13-HCG） in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 （12.5%） were found to have malignarteies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and 132-microglobulin between turnor and non-ttmaor groups, and no significant difference exists in serum levels of ferritin and 132-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.

Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.

Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy

BACKGROUND A decline in serum carbohydrate antigen 19-9(CA19-9)levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer.Neutrophil-to-lymphocyte ratio(NLR)has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer.AIM To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity.METHODS We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St.Mary’s Hospital.Patients were divided according to CA19-9 positivity(CA19-9-positive vs-negative groups)and pre-and posttreatment NLR levels.To determine cut-off value of NLR and CA19-9 reduction,time-dependent receiver operating characteristic curve was applied.We evaluated overall survival(OS)and progression-free survival(PFS)for each group using Kaplan-Meier method,and we performed multivariate analyses on the entire cohort.RESULTS We included 271 patients in this study.Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%.Multivariate analysis showed that post-treatment NLR<2.62 and reduction of≥18%of baseline CA19-9 were significantly associated with OS and PFS.Post-treatment NLR≥2.62 showed hazard ratio(HR)of 2.47[95%confidence interval(CI):1.84-3.32,P<0.001]and CA19-9 decline(≥18%)showed HR of 0.51(95%CI:0.39-0.67,P<0.001)for OS.When CA19-9-positive patients were divided into groups according to CA19-9 response(responder vs non-responder)and post-treatment NLR(<2.62 vs≥2.62),CA19-9 responder and post-treatment NLR<2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR≥2.62 group(OS 11.0 mo vs 3.9 mo,P<0.001;PFS 6.3 mo vs 2.0 mo,P<0.001).The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group.Within the CA19-9-negative group,the posttreatment NLR<2.62 group showed better survival than the post-treatment NLR≥2.62 group(OS 12.7 mo vs 7.7 mo,P<0.001;PFS 6.7 mo vs 2.1 mo,P<0.001),and post-treatment NLR showed correlation with clinical response.CONCLUSION In advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy,the combination of post-treatment NLR<2.62 and 18%decline of CA19-9 at the first response evaluation is a good prognostic marker.Post-treatment NLR<2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.

Proliferating cell nuclear antigen clamp associated factor,a potential proto-oncogene with increased expression in malignant gastrointestinal tumors

Gastrointestinal(GI)cancers,including malignancies in the gastrointestinal tract and accessory organs of digestion,represent the leading cause of death worldwide due to the poor prognosis of most GI cancers.An investigation into the potential molecular targets of prediction,diagnosis,prognosis,and therapy in GI cancers is urgently required.Proliferating cell nuclear antigen(PCNA)clamp associated factor(PCLAF),which plays an essential role in cell proliferation,apoptosis,and cell cycle regulation by binding to PCNA,is a potential molecular target of GI cancers as it contributes to a series of malignant properties,including tumorigenesis,epithelial-mesenchymal transition,migration,and invasion.Furthermore,PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer.In addition to GI cancers,PCLAF is also involved in other types of cancers and autoimmune diseases.Several pivotal pathways,including the Rb/E2F pathway,NF-κB pathway,and p53-p21 cascade,are implicated in PCLAF-mediated diseases.PCLAF also contributes to some diseases through dysregulation of the p53 pathway,WNT signal pathway,MEK/ERK pathway,and PI3K/AKT/mTOR signal cascade.This review mainly describes in detail the role of PCLAF in physiological status and GI cancers.The signaling pathways involved in PCLAF are also summarized.Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.

HCA520, A NOVEL TUMOR ASSOCIATED ANTIGEN, INVOLVED IN CELL PROLIFERATION AND APOPTOSIS

Objective: Tumor associated antigen encoding gene HCA520 (AF146019) was identified by screening a human hepatocellular carcinoma expressing cDNA library using SEREX technique. In this experiment we studied the effect of HCA520 on cell proliferation and apoptosis. Methods: Gene HCA520 was gained by PCR and transfected into 293 cells. The stable expression cells were obtained by G418 selection. The cell proliferation was measured by [3H]-TdR uptake and apoptosis assay was measured by FACS. Results: Eukaryotic expression plasmid pcDNA3-HCA520 was constructed and its stable transfectants were obtained. Overexpression of HCA520 inhibited the cell proliferation and enhanced cell apoptosis after serum deprivation. Conclusion: HCA520 is a novel tumor associated antigen that can affect cell proliferation and apoptosis.

Diagnostic value of elevated serum carbohydrate antigen 199 level in acute cholangitis secondary to choledocholithiasis

AIM To investigate the diagnostic value of abnormal serum carbohydrate antigen 199(CA199) level in acute cholangitis secondary to choledocholithiasis.METHODS In this retrospective cohort study, the clinical data of 727 patients with choledocholithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from June 2011 to June 2017 were collected. Among these patients, 258 patients had secondary acute cholangitis and served as observation group, and the remaining 569 choledocholithiasis patients served as the control group. Serum liver function indexes and tumor markers were detected in both groups, and the receiver operating characteristic(ROC) curves were constructed for markers showing statistical significances. The cutoff value, sensitivity, and specificity of each marker were calculated according to the ROC curves. RESULTS The results of liver function tests showed no significant differences between the two groups(P > 0.05). Tumor markers including serum CA125, CA153, carcinoembryonic antigen, and alpha fetoprotein levels were also not significantly different(P > 0.05); however, the serum CA199 level was significantly higher in the observation group than in the control group(P < 0.05). The ROC curve analysis showed that the area under the curve was 0.885(95%CI: 0.841-0.929) for CA199, and the cutoff value of 52.5 kU/L had the highest diagnostic accuracy, with a sensitivity of 86.8% and a specificity of 81.6%.CONCLUSION Abnormally elevated serum CA199 level has an important value in the diagnosis of acute cholangitis secondary to choledocholithiasis. It may be a specific inflammatory marker for acute cholangitis.

High level of preoperative carbohydrate antigen 19-9 is a poor survival predictor in gastric cancer

AIM:To assess the clinical significance and the prognostic value of preoperative serum carbohydrate antigen 19-9(CA 19-9)level in gastric cancer.METHODS:Between January 2005 and December2006,1960 patients underwent surgery for histologically confirmed gastric cancer.Of these,163 patients had elevated serum levels of CA 19-9 preoperatively,and1628 patients had normal serum levels of CA 19-9 preoperatively.For this study,325 patients were selected from the group of 1628 patients by age,sex,and cancer stage to serve as controls.Statistically significant differences in survival rates were calculated using the log-rank test.A P value less than 0.05 was considered statistically significant and was determined using SAS software.RESULTS:The baseline characteristics showed some differences between the two groups with regard to histology.Overall survival(OS)in the elevated and nonelevated group was 37.90 and 68.67 mo,respectively(P<0.001).N stage(P=0.001)was a significant predictor of disease-free survival by multivariate analysis.Also,N stage(P<0.001),and the presence of peritoneal metastasis(P<0.001)remained independent factors in predicting OS by multivariate analysis.Additionally,preoperative serum CA 19-9 levels were significantly associated with OS in univariate(P=0.009)and multivariate(P=0.021)analyses.CONCLUSION:Serum CA 19-9 can be considered an independent prognostic factor in predicting OS in patients anticipating surgery for gastric cancer.

HLA class Ⅱ associated with outcomes of hepatitis B and C infections

Several factors influence the clinical course of hepatitis B virus(HBV)and hepatitis C virus(HCV)infection.The human leukocyte antigen(HLA)system,the major histocompatibility complex(MHC)in humans,has been considered one of the most important host factors with respect to outcomes.To date,conventional genotyping studies have shown that HLA classⅡloci are mainly associated with spontaneous clearance of HBV and HCV.However,the specific HLA locus associated with the outcomes of hepatitis virus infection remains unclear.A recent genome-wide association study(GWAS)using a comprehensive approach for human genotyping demonstrated single nucleotide polymorphisms(SNPs)associated with the outcomes of hepatitis virus infection.Examination of large numbers of cohorts revealed that several SNPs in both HLA-DPA1 and HLADPB1 loci are associated with persistent HBV infection in Asian populations.To date,however,few studies have focused on HLA-DP because polymorphisms of HLA-DP haplotype do not vary greatly as compared with other loci of HLA.There are not enough studies to reveal the function of HLA-DP.GWAS additionally detected candidate SNPs within HLA loci associated with chronic HBV or HCV hepatitis,hepatic fibrosis,and the development of hepatocellular carcinoma.The results of one cohort were not always consistent with those of other cohorts.To solve several controversial issues,it is necessary to validate reported SNPs on HLA loci in global populations and to elucidate the HLA-allele-regulated molecular response to hepatitis virus infection.

Detection of pancreatic cancer with normal carbohydrate antigen 19-9 using protein chip technology

AIM: To develop a method to differentiate pancreatic cancer patients from healthy or benign individuals when carbohydrate antigen (CA) 19-9 is normal.

Prognostic value of increased carbohydrate antigen in patients with heart failure

AIM:To study the prognostic value of carbohydrateantigen 125(CA125) and whether it adds prognostic information to N-terminal pro-brain natriuretic peptide(NT-proBNP) in stable heart failure(HF) patients.METHODS:The predictive value of CA125 was retrospectively assessed in 156 patients with stable HF remitted to the outpatient HF unit for monitoring from 2009 to 2011.Patients were included in the study if they had a previous documented episode of HF and received HF treatment.CA125 and NT-proBNP concentrations were measured.The independent association between NT-proBNP or CA125 and mortality was assessed with Cox regression analysis,and their combined predictive ability was tested by the integrated discrimination improvement(IDI) index.RESULTS:The mean age of the 156 patients was 72 ± 12 years.During follow-up(17 ± 8 mo),27 patients died,1 received an urgent heart transplantation and 106 required hospitalization for HF.Higher CA125 values were correlated with outcomes:58 ± 85 KU/L if hospitalized vs 34 ± 61 KU/L if not(P < 0.05),and 94 ± 121 KU/L in those who died or needed urgent heart transplantation vs 45 ± 78 KU/L in survivors(P < 0.01).After adjusting for propensity scores,the highest risk was observed when both biomarkers were elevated vs not elevated(HR = 8.95,95%CI:3.11-25.73; P < 0.001) and intermediate when only NT-proBNP was elevated vs not elevated(HR = 4.15,95%CI:1.41-12.24; P < 0.01).Moreover,when CA125 was added to the clinical model with NT-proBNP,a 4%(P < 0.05) improvement in the IDI was found.CONCLUSION:CA125 > 60 KU/L identified patients in stable HF with poor survival.Circulating CA125 level adds prognostic value to NT-proBNP level in predicting HF outcomes.

Preoperative serum carbohydrate antigen 19-9 levels predict early recurrence after the resection of early-stage pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a serious disease with a poor prognosis.Only a minority of patients undergo surgery due to the advanced stage of the disease,and patients with early-stage disease,who are expected to have a better prognosis,often experience recurrence.Thus,it is important to identify the risk factors for early recurrence and to develop an adequate treatment plan.AIM To evaluate the predictive factors associated with the early recurrence of earlystage PDAC.METHODS This study enrolled 407 patients with stage I PDAC undergoing upfront surgical resection between January 2000 and April 2016.Early recurrence was defined as a diagnosis of recurrence within 6 mo of surgery.The optimal cutoff values were determined by receiver operating characteristic(ROC)analyses.Univariate and multivariate analyses were performed to identify the risk factors for early recurrence.RESULTS Of the 407 patients,98 patients(24.1%)experienced early disease recurrence:26(26.5%)local and 72(73.5%)distant sites.In total,253(62.2%)patients received adjuvant chemotherapy.On ROC curve analysis,the optimal cutoff values for early recurrence were 70 U/mL and 2.85 cm for carbohydrate antigen 19-9(CA 19-9)levels and tumor size,respectively.Of the 181 patients with CA 19-9 level>70 U/mL,59(32.6%)had early recurrence,compared to 39(17.4%)of 226 patients with CA 19-9 level≤70 U/mL(P<0.001).Multivariate analysis revealed that CA 19-9 level>70 U/mL(P=0.006),tumor size>2.85 cm(P=0.004),poor differentiation(P=0.008),and non-adjuvant chemotherapy(P=0.025)were significant risk factors for early recurrence in early-stage PDAC.CONCLUSION Elevated CA 19-9 level(cutoff value>70 U/mL)can be a reliable predictive factor for early recurrence in early-stage PDAC.As adjuvant chemotherapy can prevent early recurrence,it should be recommended for patients susceptible to early recurrence.

Prognostic significance of SUVmax and serum carbohydrate antigen 19-9 in pancreatic cancer

AIM: To investigate the prognostic significance of pretreatment standardized maximum uptake value (SUVmax) and serum carbohydrate antigen (CA)19-9 in pancreatic cancer.

Clinical characteristics and outcomes in carbohydrate antigen 19-9 negative pancreatic cancer

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a leading cause of death from cancer worldwide.Tumor markers like carbohydrate antigen 19-9(CA 19-9)have been proven valuable as a diagnostic tool and a predictor for tumor staging and response to therapy.AIM To delineate the phenotype of normal CA 19-9 PDAC according to clinical features,disease staging and prognosis as compared with high CA 19-9 PDAC cases.METHODS We performed a retrospective single-center analysis of all PDAC cases admitted in our Gastroenterology department over a period of 30 mo that were diagnosed by endoscopic ultrasound-guided tissue acquisition.Patients were divided into two groups according to CA 19-9 levels over a threshold of 37 U/mL.We performed a comparison between the two groups with regard to demographic and clinical data,biomarkers,tumor staging and 6-mo survival.RESULTS Altogether 111 patients were recruited with 29 having documented normal CA 19-9(<37 U/mL).In the CA 19-9 negative group of patients,20.68%had elevated levels of both CEA and CA 125,13.79%for CA 125 only whilst 17.24%for CEA only.The two groups had similar demographic characteristics.Abdominal pain was more frequently reported in positive vs negative CA 19-9 PDAC cases(76.83%vs 55.17%),while smoking was slightly more prevalent in the latter group(28.04%vs 31.03%).Tumors over 2 cm were more frequently seen in the positive CA 19-9 group,reflecting a higher proportion of locally advanced and metastatic neoplasia(87.7%vs 79.3%).Sixmonth survival was higher for the negative CA 19-9 group(58.62%vs 47.56%).CONCLUSION Elevated CA 19-9 at diagnosis seems to be associated with a more pronounced symptomatology,high tumor burden and poor prognosis compared to negative CA 19-9 PDAC cases.CEA and CA 125 can be adjunctive useful markers for PDAC,especially in CA 19-9 negative cases.

Hepatitis B virus persistent infection-related single nucleotide polymorphisms in HLA regions are associated with viral load in hepatoma families

BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)infections.One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation.AIM To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma(HCC).METHODS The HCC families included 301 hepatitis B surface antigen(HBsAg)carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984.Five HBV-related single nucleotide polymorphisms(SNPs)—rs477515,rs9272105,rs9276370,rs7756516,and rs9277535—were genotyped.Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation.RESULTS In the first-stage persistent HBV study,all SNPs except rs9272105 were associated with persistent infection.A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors(P<0.001)suggests that the former play a major role in persistent HBV infection.In the second-stage viral load study,we added 8 HBsAg carriers born after 1984.The 309 HBsAg carriers were divided into low(n=162)and high viral load(n=147)groups with an HBV DNA cutoff of 105 cps/mL.Sex,relationship to the index case,rs477515,rs9272105,and rs7756516 were associated with viral load.Based on the receiver operating characteristic curve analysis,genetic and nongenetic factors affected viral load equally in the HCC family cohort(P=0.3117).CONCLUSION In these east Asian adults,the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.

Tumor Carbohydrate Antigens and Strategies to Develop Cancer Vaccines and Drugs

Certain carbohydrate antigens of malignantly trans- formed cells have been identified as markers for the onset of can- cer and have become targets for the development of anticancer vaccine therapies. For tumor antigens, many carbohydrate antigens belong to T-independent （TI） antigens. Carbohydrate conjugated to protein carriers can switch TI antigen to a T-dependent （TD） anti- gen. Attempts to add an innate immune response element （such as Toll-like receptor ligand） to carbohydrate TI-antigens have also been studied. Glycosylation inhibitors or small interfering RNA have also been used for antitumor and/or antiviral agents. This review aims at describing the vast spectrum of tumor carbohydrate antigens and strategies to develop cancer vaccines and drugs.