Carbohydrate Antigen Research Articles

Multiparameter diagnostic model based on 18F-FDG positron emission tomography and serological examination for differentiating focal autoimmune pancreatitis from pancreatic ductal adenocarcinoma.

18F-fluorodeoxyglucose positron emission tomography-computerized tomography (18F-FDG PET-CT) has demonstrated high sensitivity in the diagnosis of autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC), while also exhibiting the ability to distinguish AIP from PDAC lesions. The objective of this investigation was to assess the efficacy of multiparametric 18F-FDG PET with serological examination for distinguishing focal AIP (f-AIP) from PDAC. A total of 127 patients (43 with f-AIP and 84 with PDAC) who received 18F-FDG PET-CT before treatment were retrospectively included in the cohort study conducted at two centers, Beijing Friendship Hospital and Chinese PLA General Hospital, from January 2015 to December 2021. The baseline characteristics and clinical data were collected. The metabolism parameters of 18F-FDG PET, including maximum standardized uptake value (SUVmax), tumor-to-normal liver SUV ratio (SUVR), mean SUV (SUVmean), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were evaluated. The area under the receiver operating characteristic (ROC) curve was used to evaluate the differential diagnostic efficacy. The diagnostic efficacy improvement was assessed through the integrated discriminatory improvement (IDI), net reclassification improvement (NRI), and DeLong test. Serum immunoglobulin G4 (IgG4) >280 mg/dL, carbohydrate antigen 19-9 (CA19-9) <85 U/mL, and metabolic parameters differed significantly between patients with f-AID and PDAC. The ROC curve analysis of MTV showed the highest differentiating diagnostic value [sensitivity =0.814, 95% confidence interval (CI): 0.661-0.911; specificity =0.893, 95% CI: 0.802-0.947; area under the curve (AUC) =0.890, 95% CI: 0.820-0.957]. The combined diagnostics model of serum IgG4 >280 mg/dL, CA19-9 <85 U/mL, and MTV resulted in the highest AUC of 0.991 (95% CI: 0.978-1.000; sensitivity =0.953, 95% CI: 0.829-0.992; specificity =0.964, 95% CI: 0.892-0.991). The multiparameter diagnostic model based on 18F-FDG PET and serological examination has excellent clinical value in the differential diagnosis of f-AID and PDAC.

Clinical utility of six serum tumor markers for the diagnosis of lung cancer

AbstractBackgroundWith the increasing prevalence of lung cancer, it has become imperative to identify reliable biomarkers that can aid in early detection and prognosis assessment. Therefore, we sought to investigate the potential utility of six serum tumor markers as diagnostic and prognostic tools for lung cancer patients. By analyzing a large cohort of patients with different stages and subtypes of lung cancer, we hoped to shed light on the predictive value and accuracy of each marker individually, as well as their combined performance. This study should not only provide valuable insights into the biology and pathogenesis of lung cancer but also pave the way for personalized treatment strategies based on individual patient profiles.MethodsThe serum levels of the tumor markers progastrin‐releasing peptide (ProGRP), carcinoembryonic antigen (CEA), neuron‐specific enolase (NSE), cytokeratin 19 fragment (CYFRA21‐1), carbohydrate antigen 19‐9 (CA19‐9) and squamous cell carcinoma antigen (SCCA) were meticulously assessed in a cohort comprising 324 individuals diagnosed with lung cancer and an additional 51 patients with benign lung disease. The measurements were conducted using cutting‐edge techniques such as ELISA, electrochemical luminescence, and chemiluminescence methods. Differences between groups and the impact of these markers on lung cancer diagnosis were analyzed.ResultsThe serum levels of ProGRP, NSE, and CEA were significantly higher in lung cancer patients than in patients with benign lung disease (p &lt; 0.01). NSE had the highest sensitivity for squamous cell carcinomas (SC), while CEA had the highest sensitivity for adenocarcinomas (AC). ProGRP and NSE had higher sensitivities than other markers for small cell carcinomas (SCC). Combining the six tumor markers resulted in higher sensitivities for SC (70.6%), AC (77.4%), and SCC (80%) compared with any single test. Receiver operator characteristic analysis showed that ProGRP and NSE had a greater area under the curve (AUC) in SCC (0.886 and 0.775) than SC and AC, while CEA had a higher AUC in AC (0.716), and NSE had a higher AUC than other markers in SC (0.719).ConclusionsProGRP and NSE are effective serum tumor markers for SCC, whereas CEA and NSE may aid in the diagnosis of AC and SC. Combining the detection of ProGRP, NSE, CYFRA21‐1, CEA, and SCCA significantly improves sensitivity when diagnosing lung cancer.

Arachidonic acid metabolism CYP450 pathway is deregulated in hepatocellular carcinoma and associated with microvascular invasion.

Arachidonic acid metabolism plays a crucial role in the development and progression of inflammatory and metabolic liver diseases. However, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression of key genes involved in the arachidonic acid metabolism pathway in HCC using a combination of bioinformatics, proteomics and immunohistochemistry analyses. Through a comprehensive analysis of publicly available datasets, clinical HCC tissues, and tissue microarrays, we compared the expression of hepatic arachidonic acid metabolic genes. We observed significant downregulation of cytochrome P450 (CYP450) pathway genes at both the messenger RNA and protein levels in HCC tissues compared to normal liver tissues. Furthermore, we observed a strong correlation between the deregulation of the arachidonic acid metabolism CYP450 pathway and the pathological features and prognosis of HCC. Specifically, the expression of CYP2C8/9/18/19 was significantly correlated with pathological grade (r = -.484, p < .0001), vascular invasion (r = -.402, p < .0001), aspartate transaminase (r = -.246, p = .025), gamma-glutamyl transpeptidase (r = -.252, p = .022), alkaline phosphatase (r = -.342, p = .002), alpha-fetoprotein (r = -.311, p = .004) and carbohydrate antigen 19-9 (r = -.227, p = .047). Moreover, we discovered a significant association between CYP450 pathway activity and vascular invasion in HCC. Collectively, these data indicate that arachidonic acid CYP450 metabolic pathway deregulation is implicated in HCC progression and may be a potential predictive factor for early recurrence in patients with HCC.

Phenotypic characteristics of circulating tumor cells and predictive impact for efficacy of chemotherapy in patients with pancreatic cancer: a prospective study.

Early chemoresistance and tumor mass progression are associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Circulating tumor cells (CTCs) have been studied as potential predictors of treatment response and prognosis in PDAC; however, this approach has yet to be applied in clinical practice. The aim of our study was to investigate the phenotypic characteristics of CTCs and determine their predictive value for PDAC progression. We prospectively enrolled 40 patients who were pathologically diagnosed with PDAC and collected blood samples at diagnosis, 2 months after diagnosis, and during disease progression or recurrence. We used a microfabricated filter-based enrichment system to retrieve and analyze CTCs, which were classified using immunofluorescence staining (CD45, EpCAM, and vimentin). Our study included 20 women and 20 men (median age, 66 years). Overall, 45% of the patients (18/40) had disseminated disease, and 77.5% (31/40) received chemotherapy. Multivariate analysis revealed that the total CTC count and carbohydrate antigen 19-9 level at 2 months after diagnosis were associated with disease progression (P<0.05). Linear mixed model analysis revealed that the total CTC count and vimentin-positive CTCs were significantly correlated with treatment response during chemotherapy (P=0.024 and 0.017, respectively). Kaplan-Meier analysis showed that total CTC positivity at 2 months was significantly associated with poor progression-free survival (P=0.038). Our study's findings suggest that CTCs can serve as predictive biomarkers of clinical outcomes in patients with PDAC receiving palliative chemotherapy. In particular, the total CTC count and vimentin-positive CTCs showed changes associated with the chemotherapy response.

Improving prognosis and assessing adjuvant chemotherapy benefit in locally advanced rectal cancer with deep learning for MRI: A retrospective, multi-cohort study

PurposeAdjuvant therapy is recommended to minimize the risk of distant metastasis (DM) and local recurrence (LR) in patients with locally advanced rectal cancer (LARC). However, its role is controversial. We aimed to develop a pretreatment MRI-based deep learning model to predict LR, DM, and overall survival (OS) over 5 years after surgery and to identify patients benefitting from adjuvant chemotherapy (AC). Materials and methodsThe multi-survival tasks network (MuST) model was developed in a primary cohort (n = 308) and validated using two external cohorts (n = 247, 245). An AC decision tree integrating the MuST-DM score, perineural invasion (PNI), and preoperative carbohydrate antigen 19–9 (CA19-9) was constructed to assess chemotherapy benefits and aid personalized treatment of patients. We also quantified the prognostic improvement of the decision tree. ResultsThe MuST network demonstrated high prognostic accuracy in the primary and two external cohorts for the prediction of three different survival tasks. Within the stratified analysis and decision tree, patients with CA19-9 levels > 37 U/mL and high MuST-DM scores exhibited favorable chemotherapy efficacy. Similar results were observed in PNI-positive patients with low MuST-DM scores. PNI-negative patients with low MuST-DM scores exhibited poor chemotherapy efficacy. Based on the decision tree, 14 additional patients benefiting from AC and 391 patients who received over-treatment were identified in this retrospective study. ConclusionThe MuST model accurately and non-invasively predicted OS, DM, and LR. A specific and direct tool linking chemotherapy decisions and benefit quantification has also been provided.

Predicting conversion surgery in patients with locally advanced pancreatic cancer after modified FOLFIRINOX treatment.

/Objective: FOLFIRINOX therapy (FFX) for locally advanced pancreatic cancer (LAPC) is increasingly recognized as a potent neoadjuvant therapy that enables transition to conversion surgery (CS). However, predictors of CS achievement after chemotherapy are controversial. This study aimed to demonstrate the efficacy of CS after modified FFX (mFFX) in patients with LAPC and to identify and score predictors of CS. From January 2014 to December 2018, patients with LAPC who received mFFX as a first-line treatment were screened. Patients' overall survival was compared with and without CS. Moreover, the predictors for CS were analyzed to create scores for the CS factors. Forty-three patients received mFFX, including 20 patients who underwent CS (CS group, 46.5%). R0 resection was achieved in 16 patients (80%). The median survival time was 39.2 months (95% confidence interval [CI] 17.3-53.8) for the CS group and 16 months (95% CI 10.5-22.6) for the non-CS group (P<0.001; hazard ratio 0.25, 95% CI 0.12-0.54). Since an average relative dose intensity of ≥90%, tumor reduction of ≥35%, and carbohydrate antigen 19-9 reduction of ≥70% or normalization were associated with successful transition to CS in the multivariate analysis, these factors were scored (CS score, range 0-3). All of the patients in the CS group fell into the 2-3 category, compared with 2 of 23 patients in the non-CS group (P<0.001). CS after FFX contributes to the long-term survival of patients with LAPC. The CS score could be an indicator for transition to CS.

Baseline serum tumor markers predict the survival of patients with advanced non-small cell lung cancer receiving first-line immunotherapy: a multicenter retrospective study

BackgroundThis study aimed to investigate the association between baseline serum tumor markers (STMs) (carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], cytokeratin-19 fragment [CYFRA21-1], carbohydrate antigen 19–9 [CA19-9], and carbohydrate antigen 125 [CA125]) and the efficacy of first-line immunotherapy in patients with advanced non-small cell lung cancer.MethodsThis multicenter retrospective study evaluated patients who received first-line immunotherapy between July 2017 and July 2022. The endpoints were progression-free survival (PFS) and overall survival (OS), as defined by the Response Evaluation Criteria in Solid Tumors version 1.1. We divided the patients into three groups based on STM levels: Group A ≥ threefold upper limit of normal, threefold upper limit of normal > Group B > upper limit of normal, and Group C ≤ upper limit of normal.ResultsIn total, 716 patients were included in this study. In Cox proportional hazards analyses, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung adenocarcinoma (LUAD). Except for CA19-9 level, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung squamous carcinoma (LUSC). Except for CEA and CA19-9 levels, the levels in Group A were independently associated with inferior PFS and OS in patients with LUAD and LUSC.ConclusionsSerum CEA, NSE, CYFRA21-1, and CA125 levels can predict PFS and OS in patients with LUAD and LUSC, and serum CA19-9 levels can predict PFS and OS in patients with LUAD. The higher the serum NSE, CYFRA21-1, and CA125 levels, the worse the PFS and OS in patients with LUAD and LUSC. In addition, the higher the serum CA19-9 level, the worse the OS in patients with LUAD.

Holistic Understanding of the Role of Carbohydrate Antigen 19-9 in Pancreatic Cancer Screening, Early Diagnosis, and Prognosis: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting this disease early on is crucial, and researchers have been investigating various potential biological markers, such as carbohydrate antigen 19-9 (CA 19-9), hoping to find indicators that can aid in its early detection. The primary focus of this reviewis on the diagnostic usefulness of CA 19-9 in detecting pancreatic cancer (PC) in the beginning stage and its usefulness in predicting progression. The database search of articles from PubMed, PMC, the Cochrane Library, and Google Scholar identified 227 articles published from 2013 to 2023. The keyword mix used in the search technique included terms like "CA 19-9," "pancreatic cancer," "diagnosis," and "early detection." This study provides evidence of CA 19-9's ability in detecting PDAC in the pre-diagnostic stage. But since the outcomes were inconsistent among the included trials, further analysis is required to develop standardized diagnostic criteria and methodologies. Furthermore, because of the variability of the study, it is not easy to make firm conclusions on CA 19-9's sensitivity as well as specificity in the first stage of pancreatic neoplasm. This in-depth overview of the available literature provides new insights into using CA 19-9 as a biological marker for detecting undiagnosed PC before progressing into the advanced stage, and was proven beneficial. However, this has to be shown in broader research with adequate sample size. Although it shows promise as a diagnostic tool, further study is required to confirm these findings.

The relationship between serum CA-125 level and recurrence in surgical stage 1 endometrial cancer patients.

The majority of patients diagnosed with early stage endometrial cancer have a favorable prognosis; however, approximately 10-15% experience a recurrence. Therefore, the aim of the present study was to evaluate whether post-operative carbohydrate antigen 125 (CA-125) levels could be used to predict recurrence and recurrence-free survival (RFS) in patients with surgical stage I endometrial cancer. We enrolled a total of 518 patients with stage I endometrial cancer who underwent surgical treatment between January 2010 and March 2019. Serum CA-125 levels were measured prior to surgery, as well as 6-12 months after surgery. Subsequently, the correlations between the CA-125 levels, cancer recurrence, and RFS were analyzed. Although the pre-operative CA-125 level was not associated with the risk of cancer recurrence, the post-operative CA-125 level was found to be the only independent predictor of recurrence in both univariate and multivariate analyses. Additionally, we found that a post-operative CA-125 cut-off value of 13.75 U/mL yielded the best sensitivity and specificity for predicting cancer recurrence. Patients with a post-operative CA-125 level ≥ 13.75 U/mL, and those with a level < 13.75 U/mL, had a median time to recurrence and a 5-year RFS rate of 35.5 vs. 50.5 months and 84.7 vs. 94.4%, respectively. Additionally, post-operative CA-125 levels were not found to be correlated with pre-operative levels. In patients with stage I endometrial cancer, a post-operative CA-125 level ≥13.75 U/mL was found to be significantly correlated with a higher recurrence rate, as well as a shorter RFS. Therefore, obtaining a follow-up CA-125 level within 6-12 months after staging surgery may be a promising noninvasive biomarker for predicting recurrence.

Biotinylated aptamer-based SPR biosensor for detection of CA125 antigen

Carbohydrate antigen 125 (CA125) is used for the prediction of the risk of ovarian malignancy algorithm value as an early diagnosis algorithm of ovarian cancer (OC). Hence, the detection of OC in the early stage requires techniques with high sensitivity and specificity. This work presents the development of a highly sensitive and specific aptamer-based SPR biosensor for the detection of CA125 antigen. A biotinylated CA125 aptamer (Ap) was immobilized onto a streptavidin-coated gold chip by affinity capture. Parameters affecting the response such as temperature, flow rate, and pH of flow buffer were optimized, and bioanalytical method validation elements were calculated. The linear range of the system response was 10–100 U mL−1, and the limit of detection (LOD) was found to be 0.01 U mL−1. The results affirmed that both precision and accuracy were lower than 15% for each concentration of CA125, and its recoveries were in the range of 97.5–105%. Therefore, the precision, accuracy, and recovery were acceptable for the determination of CA125 using the developed aptabiosensor. The developed Ap-based SPR technique was highly efficient for the clinical measurement of CA125 in human serum samples. In conclusion, the developed aptasensor can be an alternative for the screening and early detection of OC.

Prediction Model for Early-Stage Pancreatic Cancer Using Routinely Measured Blood Biomarkers

Accurate risk prediction models using routinely measured biomarkers-eg, carbohydrate antigen 19-9 (CA19-9) and bilirubin serum levels-for pancreatic cancer could facilitate early detection of pancreatic cancer and prevent potentially unnecessary diagnostic tests for patients at low risk. An externally validated model using CA19-9 and bilirubin serum levels in a larger cohort of patients with pancreatic cancer or benign periampullary diseases is needed. To assess the discrimination, calibration, and clinical utility of a prediction model using readily available blood biomarkers (carbohydrate antigen 19-9 [CA19-9] and bilirubin) to distinguish early-stage pancreatic cancer from benign periampullary diseases. This diagnostic study used data from 4 academic hospitals in Italy, the Netherlands, and the UK on adult patients with pancreatic cancer or benign periampullary disease treated from 2014 to 2022. Analyses were conducted from September 2022 to February 2023. Serum levels of CA19-9 and bilirubin from samples collected at diagnosis and before start of any medical intervention. Discrimination (measured by the area under the curve [AUC]), calibration, and clinical utility of the prediction model and the biomarkers, separately. The study sample comprised 249 patients in the development cohort (mean [SD] age at diagnosis, 67 [11] years; 112 [45%] female individuals), and 296 patients in the validation cohort (mean [SD] age at diagnosis, 68 [12] years; 157 [53%] female individuals). At external validation, the prediction model showed an AUC of 0.89 (95% CI, 0.84-0.93) for early-stage pancreatic cancer vs benign periampullary diseases, and outperformed CA19-9 (difference in AUC [ΔAUC], 0.10; 95% CI, 0.06-0.14; P < .001) and bilirubin (∆AUC, 0.07; 95% CI, 0.02-0.12; P = .004). In the subset of patients without elevated tumor marker levels (CA19-9 <37 U/mL), the model showed an AUC of 0.84 (95% CI, 0.77-0.92). At a risk threshold of 30%, decision curve analysis indicated that performing biopsies based on the prediction model was equivalent to reducing the biopsy procedure rate by 6% (95% CI, 1%-11%), without missing early-stage pancreatic cancer in patients. In this diagnostic study of patients with pancreatic cancer or benign periampullary diseases, an easily applicable risk score showed high accuracy for distinguishing early-stage pancreatic cancer from benign periampullary diseases. This model could be used to assess the added diagnostic and clinical value of novel biomarkers and prevent potentially unnecessary invasive diagnostic procedures for patients at low risk.

Effects of coagulation function indicators and tumor markers on diagnosis and clinicopathological characteristics of endometrial cancer.

Endometrial cancer is currently the prevalent malignant cancer worldwide. Diagnostic efficiency of tumor markers is limited, and coagulation function indicators in endometrial cancer are less concerned. This study attempted to evaluate the effects of coagulation function indicators and tumor markers on the clinical diagnosis and clinicopathological characteristics of patients with endometrial cancer. The retrospective analysis compared the differences in coagulation function indicators and tumor markers among 175 patients with endometrial cancer and 170 healthy women from January 2020 to October 2022. Compared to the healthy control, the levels of D-dimer, fibrinogen, human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125), CA153, and CA199 in patients with endometrial cancer were significantly higher (P < 0.05). Univariate and multivariate regression analyses revealed that abnormal levels of D-dimer, fibrinogen, HE4, CA125, CA153, and CA199 were related risk factors affecting the incidence of endometrial cancer. Receiver operating characteristic curve analysis exhibited that the area under the curve (0.931) and accuracy (85.2%) of combined diagnosis of coagulation function indicators (D-dimer, fibrinogen) and tumor markers (HE4, CA125, CA153, CA199) were the highest, and its sensitivity (82.3%) and specificity (88.2%) were higher than any single or combined indicators of four tumor markers. Moreover, relative expression levels of the combined indicators were significantly different among clinicopathological characteristics that had the highest predictive value in the FIGO stage (P < 0.001). D-dimer and fibrinogen represent potential diagnostic factors for endometrial cancer. The combination of coagulation function indicators and tumor markers exhibited high diagnostic value in endometrial cancer, as well as predictive value for clinicopathological characteristics.

Clinical value of combined serum CA125, NSE and 24-hour urine VMA for the prediction of recurrence in children with neuroblastoma

BackgroundIn this study, we intend to retrospectively analyze the clinical data of postoperative neuroblastoma children, including the results of follow-up examinations and laboratory tests, to explore the clinical value of combined serum Carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE) and 24-hour urine vanillylmandelic acid (VMA) levels at baseline for the prediction of recurrence in children with neuroblastoma.Methods265 children with neuroblastoma were successfully followed up, including 163 cases without recurrence (non-recurrence group) and 102 cases with recurrence (recurrence group). The levels of 24-hour urine VMA were determined using spectrophotometric methods. Additionally, the serum levels of CA125 and NSE were measured using electrochemiluminescence immunoassay.ResultsThe serum CA125, NSE and 24-hour urine VMA levels were significantly higher in the recurrence group than in the non-recurrence group. It demonstrated a significant positive correlation between the levels of serum CA125, NSE, and 24-hour urine VMA in all children with neuroblastoma. All children in stage IV of neuroblastoma had the highest level of serum CA125, NSE and 24-hour urine VMA and vice versa. The combined CA125, NSE and VMA had significantly better sensitivity and specificity than an individual marker.ConclusionsCombined serum CA125, NSE and 24-hour urine VMA had the potential to predict neuroblastoma recurrence more effectively.

Association of normalization of postoperative carbohydrate antigen 125 levels with treatment failure following uterine artery embolization for adenomyosis.

To investigate the association between carbohydrate antigen 125 (CA125) level and adenomyosis treatment failure (TF) after uterine artery embolization (UAE). We evaluated 224 patients with symptomatic adenomyosis who underwent UAE between January 2016 and December 2020. Improvements in dysmenorrhea and menorrhagia were assessed on the basis of symptom relief criteria. The factors associated with TF were investigated using a multivariate logistic regression model. Patients were analyzed for preoperative CA125 levels, postoperative CA125 levels, and the normalization of postoperative CA125 levels. Long-term symptom relief and quality of life after UAE were compared between the groups. During the 24-month follow-up, 50 patients (22.3%) experienced TF. Compared to patients in the non-TF group, those in the TF group had significantly higher preoperative and postoperative CA125 levels (p < 0.05). Multivariate analysis revealed that failure to normalize postoperative CA125 levels was independently associated with an increased risk of TF (34.7% vs. 8.5%, p < 0.001; hazard ratio 3.953, 95% confidence interval 1.567-9.973, p = 0.004). After a 3-month follow-up period, patients who normalized their CA125 levels were more likely to achieve complete necrosis on magnetic resonance imaging than those who did not (82.1% vs. 56.8%, p < 0.001). Normalization of postoperative CA125 levels was significantly associated with fewer symptoms and better quality of life 12 months after UAE (p < 0.05). Following UAE, normalization of postoperative CA125 levels, rather than absolute values, was the strongest predictive marker of TF.

Risk Stratification of Pancreatic Ductal Adenocarcinoma Patients Undergoing Curative-Intent Surgery after Neoadjuvant Therapy.

Clinical prognostic criteria using preoperative factors were not developed for post-neoadjuvant therapy (NAT) surgery of pancreatic ductal adenocarcinoma (PDAC). We aimed to identify preoperative factors associated with overall survival (OS) in PDAC patients who underwent post-NAT curative-intent surgery and develop risk stratification criteria. Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of computed tomography (CT) findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analysis was used to select preoperative variables associated with OS. We developed risk stratification criteria composed of the significant preoperative variables, i.e., post-NAT response criteria. We compared the discrimination performance of post-NAT response criteria with that of post-NAT pathological (yp) American Joint Cancer Committee TNM staging system. One hundred forty-five PDAC patients were included. Stable or increased tumor size on CT (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.58 to 4.21; p < 0.001) and elevated preoperative carbohydrate antigen 19-9 (CA19-9) level (HR, 1.98; 95% CI, 1.11 to 3.55; p=0.021) were independent factors of OS. The OS of the patient groups stratified by post-NAT response criteria which combined changes in tumor size and CA19-9 showed significant difference (p < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068; 95% CI, -0.012 to 0.142). "Any degree of decrease in tumor size on CT" and CA19-9 normalization or staying normal were independent favorable factors of OS. The combination of the two factors discriminated OS comparably to ypTNM staging.

Clinical Value of Circulating microRNAs in Diagnosis and Prognosis of Pancreatic Cancer: A Systematic Review.

Pancreatic cancer (PC) is one of the most common cancers and has a high mortality rate due to high invasiveness and rapid progression. Microribonucleic acid (microRNA) plays an essential role in diagnosing PC in the early stages, which improves the five-year survival rate. This systematic review aims to highlight the different subtypes of serum and plasma microRNAs and panel-based assays of microRNAs and how they play a crucial role in the diagnosis and prognosis of PC as a high-sensitive and specific novel biomarker. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines, an in-depth search was performed by using regular keywords and major Medical Subject Heading (MeSH) keywords in PubMed (MEDLINE), PubMed Central, Google Scholar, Science Direct, and Cochrane Library for articles related to this topic and published between 2013 and 2023, up to April 18, 2023. Further eligibility criteria and quality assessment tools were employed to assess the risk of bias, and 13 articles were finalized to be used in this review. The chosen articles included five cross-sectional studies, six systematic reviews and meta-analyses, and two literature reviews. This review provides strong evidence of the usage of microRNA for early diagnosis. It can also be used to exclude differential diagnoses of other diseases, and its prognostic value for determining metastasis and therapeutic efficacy in PC patients. Also, combining microRNA panels with carbohydrate antigen 19.9 (CA19-9) improves the sensitivity and specificity of microRNA as a biomarker.

Serum components influence antibody reactivity to glycan and DNA antigens

We previously generated three types of anti-glycan monoclonal IgM antibodies that react with certain structures on the glycans of glycosphingolipids and glycoproteins. As the nucleotide sequences for the variable regions of these IgM antibodies showed homology with those of anti-DNA antibodies deposited in public databases, we analyzed the reactivity of the anti-glycan IgM antibodies to DNA by ELISA. We found that anti-α2,6-sialyl LacNAc IgM in the supernatant of a hybridoma culture cross-reacted with DNA, and after purification of the IgM by zirconia column chromatography, the highly purified IgM showed increased cross-reactivity to DNA. As most of the contaminating bovine serum proteins in the culture supernatant were removed by the purification process, it is likely that a part of the removed components influences antibody reactivity to DNA. Purified anti-DNA antibodies prepared from lupus model NZB/W F1 and MRL/lpr mouse sera and normal human serum were then analyzed, and similar results showing increased reactivity to DNA were obtained. Furthermore, ELISA using these purified antibodies and various carbohydrate antigens showed that the antigen-binding specificity of these antibodies was altered by the purification process from serum-containing antibody preparations. Our results indicate that mammalian serum contains components that strongly influence antibody reactivity to carbohydrate antigens, including DNA.

Diagnostic value of serum human epididymis protein 4, carbohydrate antigen 125 and their combination in endometrial cancer: A meta-analysis.

To systematically analyze the value of human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the diagnosis of endometrial cancer, so as to provide evidence-based medical evidence for the selection of serum tumor markers in the early screening of endometrial cancer. We comprehensively searched relevant literature in the Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, VIP, WanFang, and CBM from the date of establishment to November 31, 2021. Quality assessment of diagnostic accuracy studies 2 was applied to evaluate the quality of the included literature. We used Stata 16.0 to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and plot summary receiver operating characteristic curve, as well as to assess diagnostic accuracy using the area under the curve (AUC). A total of 25 studies, including 1980 patients and 2345 controls, were included in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 were 0.58 (95% CI 0.52-0.63), 0.95 (95% CI 0.92-0.97), 11.57 (95% CI 6.88-19.48), 0.45 (95% CI 0.39-0.51), 25.92 (95% CI 14.84-45.26), and 0.80 (95% CI 0.76-0.83), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of CA125 were 0.41 (95% CI 0.34-0.49), 0.91 (95% CI 0.85-0.95), 4.55 (95% CI 2.73-7.58), 0.65 (95% CI 0.57-0.74), 7.03 (95% CI 3.92-12.62), and 0.68 (95% CI 0.64-0.72), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 + CA125 were 0.67 (95% CI 0.60-0.73), 0.92 (95% CI 0.87-0.95), 8.59 (95% CI 5.32-13.86), 0.36 (95% CI 0.30-0.44), 23.80 (95% CI 13.86-40.86), and 0.85 (95% CI 0.82-0.88), respectively. This Meta-analysis found that HE4 alone or in combination with CA125 showed better diagnostic efficacy than CA125, regardless of clinical stage and pathological type. HE4 + CA125 had slightly higher diagnostic efficiency than HE4, but did not show significant advantages. While the studies were heterogeneous, the credibility of the findings needs to be further confirmed by more homogeneous, prospective, and large sample size studies.

An autopsy case of alpha-fetoprotein-producing large duodenal adenocarcinoma.

We report an autopsy case of a large duodenal adenocarcinoma that produced alpha-fetoprotein (AFP). The patient was a man in his 70s with diabetes mellitus. He presented with epigastralgia and was referred to our hospital. Upper gastrointestinal endoscopy and abdominal computed tomography revealed a large tumor of 11cm in diameter in the descending limb of the duodenum. A tumor biopsy showed poorly differentiated adenocarcinoma. Although his carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were within the normal range, his AFP levels were significantly elevated (42,078.4ng/mL). Due to vascular invasion, curative resection was not feasible, and chemotherapy was chosen as the treatment option. After gastrojejunostomy was performed to enable oral intake, one cycle of modified leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) therapy was administered. However, it proved ineffective, and the patient's anorexia gradually worsened. Ultimately, he succumbed to the progression of cancer cachexia. Autopsy findings revealed a 14-cm-long duodenal carcinoma primarily located in the duodenal bulb, with direct invasion into the stomach, pancreas, and liver. A pathological examination confirmed a diagnosis of poorly differentiated adenocarcinoma with AFP production. Duodenal cancer is rare, and AFP-producing duodenal cancer is even rarer, with only 21 reported cases, including our own. We present this autopsy case of AFP-producing duodenal adenocarcinoma and review the cases reported in the relevant literature.

Tumor-Associated Extracellular Microvesicles with Fluorine-Modified Carbohydrate Antigens Trigger a Stronger Antitumor Immune Response.

Abnormal glycosylation is a hallmark of tumor development, and tumor-associated carbohydrate antigens are potential immune targets for tumor therapy. Tumor-associated extracellular microvesicles are subcellular vesicles released from cell membranes that have immunogenicity similar to that of precursor cells. However, unmodified tumor-derived microvesicles have weaknesses, such as low immunogenicity, poor biostability, and short half-life in vivo. For the first time, we herein generated extracellular microvesicles containing modified tumor-associated carbohydrate antigens by constructing a cell line with highly expressed antigen-processing enzymes utilizing fluorine-modified monosaccharide substrates via a metabolic oligosaccharide engineering strategy. The microvesicles were applied to tumor immunity, achieving enhanced immunoprophylaxis and immunotherapy effects. Furthermore, the mechanisms of antitumor immunity were explored. Our findings may provide new insights into the adhibition of suitably modified extracellular microvesicles and the development of more effective carbohydrate-based anticancer vaccines.