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.

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.

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.

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.

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.

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.

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.METHODS:Forty-one serum samples from patients with pancreatic lesions and blood samples from 20 healthy individuals were collected at the first stage of the experiment according to the enrolment criteria.General characteristics and some clinical features were carefully compared to ensure that the results were reasonable.All the blood samples were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS)combined with CM10 chips and a related bioinformatics analysis program to generate diagnostic models with different proteins.Forty-seven consecutive samples were tested at the next stage to verify the veracity and efficiency of the models.RESULTS:The sex,age,and serum CA19-9 levels among the three groups(malignant,benign,and healthy)were statistically matched(P values were 0.957,0.145,and 0.382,respectively).Two patterns were generated.Pattern 1 with four proteins theoretically had a specificity and sensitivity of 100%in distinguishing pancreatic cancer from healthy individuals,while it was 86.7%and86.4%,respectively,in the subsequent practical verification.The positive predictive value(PPV)of the model was86.4%.One of the four proteins was expressed highly in pancreatic cancer while the other three were expressed weakly.Pattern 2 consisted of six proteins that showed a specificity of 70.0%and sensitivity of 77.3%for differentiating malignancy from benign tumors.Its PPV reached85.0%.Only one of these six proteins showed high expression in the malignant group.CONCLUSION:SELDI-TOF-MS may facilitate diagnosis or differential diagnosis of pancreatic cancer when CA19-9 is normal.Pattern 1 may serve as a useful screening tool.

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.

Carbohydrate antigen 19-9 — tumor marker: Past, present, andfuture

Carbohydrate antigen 19-9 (CA 19-9) is a cell surface glycoprotein complex mostcommonly associated with pancreatic ductal adenocarcinoma (PDAC). Koprowskifirst described it in 1979 using a mouse monoclonal antibody in a colorectalcarcinoma cell line. Historically, it is one of the most commonly used tumormarkers for diagnosing, managing, and prognosticating PDAC. Additionally,elevated CA 19-9 levels are used as an indication for surgery in suspected benignpancreatic conditions. Another common application of CA 19-9 in the biliary tractincludes its use as an adjunct in diagnosing cholangiocarcinoma. However, itsclinical value is not limited to the hepatopancreatobiliary system. The reality isthat the advancing literature has broadened the clinical value of CA 19-9. Thepotential value of CA 19-9 in patients' workup extends its reach to gastrointestinalcancers – such as colorectal and oesophageal cancer – and further beyond thegastrointestinal tract - including urological, gynecological, pulmonary, andthyroid pathologies. Apart from its role in investigations, CA 19-9 presents apotential therapeutic target in PDAC and acute pancreatitis. In a bid toconsolidate its broad utility, we appraised and reviewed the biomarker’s currentutility and limitations in investigations and management, while discussing thepotential applications for CA 19-9 in the works for the future.

Carbohydrate antigen 19-9 as a novel prognostic biomarker in distal cholangiocarcinoma

BACKGROUND Distal cholangiocarcinoma(DCC)presents as one of the relatively rare malignant tumors in the digestive system and has a poor long-term prognosis.Curative resection is currently the most appropriate therapy for patients with DCC because of the lack of effective adjuvant therapies.Therefore,it is important to accurately predict the prognosis for formulating a reasonable treatment plan and avoiding unnecessary surgical trauma.AIM To minimize the interference of obstructive jaundice on carbohydrate antigen 19-9(CA19-9)level by adapting CA19-9 toγ-glutamyltransferase(GGT)as an indicator,to determine the strong associations between CA19-9/GGT and postoperative neoplasm recurrence and long-term outcome of DCC.METHODS We enrolled 186 patients who were diagnosed with DCC between January 2010 and December 2019 and performed radical excision with strict criteria as follows in our hospital.Receiver operating characteristic curves were drawn according to preoperative CA19-9/GGT and 1-year survival.Based on this,patients were divided into two groups(group 1,low-ratio,n=81;group 2,high-ratio,n=105).Afterwards,by the way of univariate and multivariate analysis,the risk factors influencing postoperative tumor recrudesce and long-term prognosis of patients with DCC were screened out.RESULTS Optimum cut-off value of CA19-9/GGT was 0.12.Patients in group 2 represented higher CA19-9 and lymphatic metastasis rate accompanied by lower GGT,when compared with group 1(P<0.05).The 1-,3-and 5-year overall survival rates of patients in groups 1 and 2 were 88.3%,59.2%and 48.1%,and 61.0%,13.6%and 13.6%,respectively(P=0.000).Multivariate analysis indicated that CA19-9/GGT,lymphatic metastasis and tumor differentiation were independent risk factors for tumor recurrence and long-term prognosis of DCC.CONCLUSION Elevation of CA19-9/GGT performed better as a biomarker of aggressive carcinoma and predictor of poor clinical outcomes by reducing the effect of obstruction of biliary tract on CA19-9 concentration in patients with DCC.

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.

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.

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.

Ciliated hepatic foregut cyst with high intra-cystic carbohydrate antigen 19-9 level

A ciliated hepatic foregut cyst(CHFC)is a rare foregut developmental malformation usually diagnosed in adulthood.Five percent of reported cases of CHFC transform into squamous cell carcinoma.We report the presentation,evaluation,and surgical management of a symptomatic 45-year-old male found to have a 6.2 cm CHFC.Contrast tomography-guided fine-needle aspirationdemonstrated columnar,ciliated epithelium consistent with the histologic diagnosis of CHFC.The intracystic levels of carbohydrate antigen(CA)19-9 and carcinoembryonic antigen(CEA)were extremely high(978118U/m L and 973μg/L,respectively).Histologically,the wall of the cyst showed characteristic pseudopapillae lined with a ciliated stratified columnar epithelium,underlying smooth muscle,an outer fibrous layer and no atypia.Immunohistochemistry for CA19-9 and CEA was positive.This is the first case report of a CHFC in which levels of CA 19-9 and CEA were measured.Our findings suggest that a large sized multilocular cyst and elevated cyst CA19-9 and CEA levels do not exclude a CHFC from consideration in the diagnosis.CHFCs should be included in the differential diagnosis of hepatic lesions.Accurate diagnosis of a CHFC is necessary given its potential for malignant transformation,and surgical excision is recommended.

Endoscopic ultrasonography in patients with elevated carbohydrate antigen 19-9 of obscure origin

AIM:To evaluate the efficacy of endoscopic ultrasonography(EUS) in patients with elevated carbohydrate antigen(CA) 19-9 levels of obscure origin.METHODS:Patients who had visited Pusan National University Hospital because of elevated serum CA 19-9 levels,between January 2007 and December 2009,were retrospectively enrolled.EUS had been performed on all subjects,in addition to routine blood tests,endoscopy,abdominal computed tomography(CT) and other clinical exams,which had not revealed any abnormal findings suggestive of the origin of the elevated CA 19-9 levels.RESULTS:Of the 17 patients,gallbladder sludge was detected in 16 patients(94.1%) and common bile duct sludge was observed in 3 patients(17.6%).After the administration of ursodeoxycholic acid to 12 of the patients with gallbladder sludge,CA 19-9 levels normalized in 6 of the patients after a median of 4.5 mo.CONCLUSION:EUS is a useful diagnostic method for patients with elevated CA 19-9 levels of obscure origin,even if the reason for abnormal levels of this serum marker cannot be determined through prior examinations,including abdominal CT.

Significance of carbohydrate antigen 50 expression in colorectal carcinoma

Objective To evaluate the significance of carbohydrate antigen 50(CA50)expression in colorectal carcinoma.Methods Immunohistochemical staining was used to detect CA50 expression in 10 cases of normal colorectal mucosa and 40 cases of cancer mucosa.Results The expression of CA50 increased in normal colorectal mucosa,cancer distant mucosa,cancer adjacent mucosa and cancer mucosa,and there were significant differences among them(P<0.05).The expression of CA50 in colorectal carcinoma was correlated with the degree of differentiation,Duke’s stage and lymphatic metastases(P<0.05).Conclusion The expression of CA50 can be used as a valuable index in evaluating the biological characteristics and prognosis of colorectal carcinoma.

Diagnostic value of elevated serum carbohydrate antigen 125 level in sarcoidosis

BACKGROUND Sarcoidosis is a multisystem disorder with unknown etiology, and it predominantly affects the lungs and intrathoracic lymph nodes. For patients with atypical clinical manifestations, the diagnosis of sarcoidosis is difficult and specific biomarkers may play an important role in assisting diagnosis. Previous research has demonstrated a correlation between sarcoidosis and increased carbohydrate antigen 125(CA125), but remains a lack of large cohort studies to validate this observation.AIM To compare serum CA125 levels in sarcoidosis patients and healthy controls, and explore whether CA125 can be used as a biomarker for the diagnosis of sarcoidosis.METHODS In this study, the serum CA125 levels were measured by enzyme-linked immunosorbent assay in 108 consecutive sarcoidosis patients between June 2016 and December 2020(31 males, 77 females;age at diagnosis 49.69 ± 9.10 years) and 112 healthy subjects. Data on the C-reactive protein, erythrocyte sedimentation rate, and angiotensin-converting enzyme were also collected. The association of serum CA125 levels with clinical, radiological, and respiratory functional characteristics was analyzed between patient groups with CA125 ≤ 35 U/mL or CA125 >35 U/mL.RESULTS We found that serum CA125 levels were higher in sarcoidosis patients compared to healthy controls(median: 44.78 vs 19.11 U/mL, P < 0.001). The area under the receiver operator characteristic was 0.9833(95%CI: 0.9717-0.9949), and the best cutoff point was 32.33 U/mL. The elevated serum CA125 was notably associated with the percentage of predicted forced vital capacity(FVC%) and neutrophil-to-lymphocyte ratio(P =0.043 and P = 0.038, respectively) in sarcoidosis patients. Multivariate analysis revealed that FVC%was a statistically notable predictor of elevated serum CA125(P = 0.029). Also, our research revealed that compared to patients with Stage I of radiology classification, patients with Stage Ⅱ and Ⅲ showed a higher concentration of serum CA125(46.16 ± 8.32 vs 41.00 ± 6.04 U/mL, P =0.005, and 47.92 ± 10.10 vs 41.00 ± 6.04 U/mL, P = 0.002, respectively).CONCLUSION Serum CA125 was highly increased in sarcoidosis patients and showed high efficiency for noninvasive diagnosis of the disease. In addition, abnormally elevated serum CA125 was correlated with pulmonary function and radiological Scadding’s classification of sarcoidosis.

Diagnostic value and clinical significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio combined with carbohydrate antigen in endometrial carcinoma

Background:To explore diagnostic value and clinical significance of preoperative neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)combined with serum carbohydrate antigen(CA),including CA125,CA153 and CA199,in endometrial cancer(EC).Methods:The clinical data of 135 patients who underwent endometrial pathology examination in our hospital from January 2014 to June 2019 were retrospectively analyzed,including 65 cases of EC,40 cases of proliferative endometrial lesions and 50 cases of normal endometrium.Blood routine analyzer and electrochemical luminescence method were used to detect 5 parameters of NLR,PLR,CA125,CA153 and CA199 in these patients.The study explored the relationship between the five indicators and different levels of endometrial lesions,and analyzed their relationship with clinical pathological characteristics of EC patients.The diagnostic efficacy of NLR,PLR,CA,NLR combined CA,PLR combined CA was evaluated by receiver operating curve(ROC)combined with logistic regression equation.Results:The expression of the five parameters was different in different levels of endometrial lesions,and the expression level increased with the increase of endometrial lesion level.The difference among the three groups was statistically significant(P<0.05).CA125 level was related to International Federation of Gynecology and Obstetrics(FIGO)stage,lymph node metastasis and ki-67 index.CA153 level was related to ki-67 index.CA199 was related to FIGO stage,tissue differentiation and lymph node metastasis.NLR was related to FIGO stage,pathological type,tissue differentiation,myometrial invasion and lymph node metastasis.PLR was correlated with tissue differentiation,and the differences were statistically significant(P<0.05).The diagnosis of NLR combined with CA was the largest area under ROC curve(0.940),and its accuracy,sensitivity and specificity were higher than those of individual parameters and NLR combined with CA.Conclusion:NLR,PLR,CA125,CA153 and CA199 were highly expressed in EC and were correlated with clinical pathological data of EC patients respectively.NLR and PLR combined with CA could significantly improve the diagnostic efficiency of EC,providing clinical reference value for EC screening,therapeutic effect evaluation and disease progression evaluation.

THE CLINICAL SIGNIFICANCE OF MONITORING CARBOHYDRATE ANTIGEN CA50 IN COLORECTAL CARCINOMA

In order to iuvestigate the possibl. involvemeut of the antigen CA5o in petlents with colorectal carcinoma, the carbohydrate antigen CA50 serum vaiue. was examined in 30 normal individuals, 27 Patients with benign colomtal diseares and 66 Patieots with coloradoal cortinoma by lmmunoradiometric assay (IRMA). The results shoed that the serum CA50 value in patients with coloretalcarcinoma was significantly higher than that in petients with benign colorectal diseeees or in normalcontrol group (P< 0. 01). It significaotly declined after radical operation was performed (P<0. 01). However, no significant change was noted arter Palliative operation (P > 0. 05) and elevatedlevels noted with tumor recurrence. We concluded that the measurement of serum CA50 may be auseful marker for diagnosis and prognostic evaluation or Patients with colorectal carcinoma.