BACKGROUND:There are numerous controversies surrounding the diagnosis of matrix metalloproteinases (MMPs) in pancreatic cancer (PC). Consequently, this study conducts the first comprehensive meta-analysis evaluating the diagnostic performance of MMP family members in PC, highlight potential biomarkers, and investigate sources of heterogeneity. METHOD:Articles on the MMP family and PC diagnosis were retrieved from PubMed and Web of Science. Diagnostic accuracy was assessed using sensitivity (SEN) and specificity (SPE). Threshold effects, heterogeneity (via meta-regression and subgroup analyses), and result robustness (via sensitivity analysis) were evaluated. Publication bias was examined using Deeks' funnel plot. RESULT:This meta-analysis included 48 studies from 23 articles, covering 12 types of MMP. The aggregated SEN, SPE, and area under the curve (AUC) for MMPs in diagnosing PC ranged from 0.61 to 0.76, 0.66 to 0.78, and 0.7273 to 0.8840, respectively. Meta-regression identified sample type as a major contributor to heterogeneity, with tissue-based MMPs showing markedly superior diagnostic performance compared to serum or plasma-based assays. Overall, MMPs showed potential diagnostic value, but their accuracy remains moderate and requires further validation in larger, well-designed studies. CONCLUSION:MMPs represent potential candidates for PC diagnosis, but current evidence is insufficient for clinical application, requiring further prospective studies.

Supplementary Figure S2: Samples (n=192) from GSE22058 were clustered and analyzed to detect the presence of outliers. Sample clustering demonstrated that two outliers (GSM548410 and GSM548460) need to be removed and the remaining samples (n=190) were applied for subsequent analyses (Supplementary Figure S2A). The scale-free modules were constructed by the optimal threshold of β=4 (Supplementary Figure S2B). Genes were divided into 16 modules by the thresholding power (Supplementary Figure S2C). The blue module had the highest correlation with the sample traits (r=0.93, P<0.001) (Supplementary Figure S2D) and the genes in this module were highly correlated with clinical information (cor=0.98, P<0.001) (Supplementary Figure S2E).

Supplementary Table S4: The AUC of these four TAAbs for identifying HBV-HCC patients from CHB patients ranged from 0.693-0.739. Among them, anti-DUSP6 showed the highest diagnostic ability, with an AUC of 0.739 (95% CI [confidence interval]: 0.694-0.785). The diagnostic capability of anti-PCNA was the poorest, with an AUC of 0.693 (95% CI: 0.645-0.741). The AUC of four candidate TAAbs in differentiating between HBV-HCC and HBV-LC patients ranged from 0.589 to 0.624. Among them, anti-PCNA had the most diagnostic capacity, with an AUC of 0.624 (95% CI: 0.569-0.679). Anti-CDC37L1 had the least diagnostic capability, with an AUC of 0.589 (95% CI: 0.533-0.645).

Background:Gastrointestinal tumors represent a significant component of the cancer burden in Asia. This study aims to evaluate the burden of gastrointestinal tumors in Asia from 1990 to 2021 using data from the Global Burden of Disease Study 2021 (GBD 2021). Methods:The absolute incidence, mortality, and disability adjusted life years (DALYs) number and rate of six gastrointestinal tumors(colon and rectum cancer (CRC), stomach cancer (SC), pancreatic cancer (PC), esophageal cancer (EC), liver cancer (LC) and gallbladder and biliary tract cancer (GBTC)) in 48 Asian countries were extracted from GBD 2021. Differences were analyzed based on gender, age, year, location and socio-demographic index (SDI). Results:In 2021, SC accounted for the highest disease burden in Asia (DALYs=16.41million [95% UI: 13.70, 19.62]). From 1990 to 2021, the age-standardized incidence rates of EC, LC, and SC in Asia declined, while the incidence rates of CRC and PC increased significantly, with CRC showing the largest rise (AAPC=1.08 [95% CI: 1.02 to 1.12]). Gastrointestinal tumors DALY rates peaked at age 70 and above, with males generally exhibiting higher rates than females. Furthermore, East Asia bears a higher burden compared to other Asian subregions. A higher SDI correlates with increased DALY rates for PC, but no linear relationship was observed for other gastrointestinal tumors. Conclusion:The burden of gastrointestinal tumors in Asia remains high and may continue to increase. Therefore, effective prevention and treatment measures are essential to address the challenge posed by gastrointestinal tumors.

PURPOSE:The relationship between circulating 25-hydroxyvitamin D [25(OH)D] and pancreatic cancer has been well studied but remains unclear. The purpose of this study was to elucidate the association between circulating 25(OH)D and pancreatic cancer by using a meta-analytic approach.METHODS:PubMed, Embase, and Wed of Science databases were searched through October 15, 2022. A random or fixed-effects model was used to estimate the pooled odds ratio (OR), risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs).RESULTS:A total of 16 studies including 529,917 participants met the inclusion criteria, of which 10 reported incidence and 6 reported mortality. For the highest versus lowest categories of circulating 25(OH)D, the pooled OR of pancreatic cancer incidence in case-control studies was 0.98 (95% CI 0.69-1.27), and the pooled HRs of pancreatic cancer mortality in cohort and case-control studies were 0.64 (95% CI 0.45-0.82) and 0.78 (95% CI 0.62-0.95), respectively. The leave-one-out sensitivity analyses found no outliers and Galbraith plots indicated no substantial heterogeneity.CONCLUSION:Evidence from this meta-analysis suggested that high circulating 25(OH)D levels may be associated with decreased mortality but not incidence of pancreatic cancer. Our findings may provide some clues for the treatment of pancreatic cancer and remind us to be cautious about widespread vitamin D supplementation for the prevention of pancreatic cancer.

Supplementary Table S3: Samples from the training set (116 HBV-HCC samples, 124 HBV-LC samples, and 157 CHB samples) were used to construct a predictive model and samples from the test set (78 HBV-HCC samples, 82 HBV-LC samples, and 106 CHB samples) were used to verify the stability of the model. The characteristics of samples in the training and test sets are shown in Supplementary Table S3.

Background: Esophageal squamous cell carcinoma (ESCC) is a deadly cancer with no clinically ideal biomarkers for early diagnosis. The objective of this study was to develop and validate a user-friendly diagnostic tool for early ESCC detection. Methods: The study encompassed three phases: discovery, verification, and validation, comprising a total of 1309 individuals. Serum autoantibodies were profiled using the HuProtTM human proteome microarray, and autoantibody levels were measured using the enzyme-linked immunosorbent assay (ELISA). Twelve machine learning algorithms were employed to construct diagnostic models, and evaluated using the area under the receiver operating characteristic curve (AUC). The model application was facilitated through R Shiny, providing a graphical interface. Results: Thirteen autoantibodies targeting TAAs (CAST, FAM131A, GABPA, HDAC1, HDGFL1, HSF1, ISM2, PTMS, RNF219, SMARCE1, SNAP25, SRPK2, and ZPR1) were identified in the discovery phase. Subsequent verification and validation phases identified five TAAbs (anti-CAST, anti-HDAC1, anti-HSF1, anti-PTMS, and anti-ZPR1) that exhibited significant differences between ESCC and control subjects (P < 0.05). The support vector machine (SVM) model demonstrated robust performance, with AUCs of 0.86 (95% CI: 0.82-0.89) in the training set and 0.83 (95% CI: 0.78-0.88) in the test set. For early-stage ESCC, the SVM model achieved AUCs of 0.83 (95% CI: 0.79-0.88) in the training set and 0.83 (95% CI: 0.77-0.90) in the test set. Notably, promising results were observed for high-grade intraepithelial neoplasia, with an AUC of 0.87 (95% CI: 0.77-0.98). The web-based implementation of the early ESCC diagnostic tool is publicly accessible at https://litdong.shinyapps.io/ESCCPred/. Conclusion: This study provides a promising and easy-to-use diagnostic prediction model for early ESCC detection. It holds promise for improving early detection strategies and has potential implications for public health.

Supplementary Figure S4: These four candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts. In the initial verification of candidate TAAbs in 120 sera, the expression of all four TAAbs was significantly different between the HBV-HCC and CHB groups (P<0.001) (Supplementary Figure S4A). These four TAAbs were further validated in a large dataset (663 sera). The results showed that the expression of four TAAbs was significantly different in the pairwise comparisons between the three groups (P<0.01), and the expression was highest in the HBV-HCC group and lowest in the CHB group (Supplementary Figure S4B).

Abstract The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. This study was divided into four phases: discovery, verification, validation, and modeling. A total of four candidate tumor-associated autoantibodies (TAAb; anti-ZIC2, anti-PCNA, anti-CDC37L1, and anti-DUSP6) were identified by human proteome microarray (52 samples) and bioinformatics analysis. Subsequently, these candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts (120 samples for verification and 663 samples for validation). The AUC for these four TAAbs to identify patients with HBV-HCC from chronic hepatitis B (CHB) patients ranged from 0.693 to 0.739. Finally, a diagnostic panel with three TAAbs (anti-ZIC2, anti-CDC37L1, and anti-DUSP6) was developed. This panel showed superior diagnostic efficiency in identifying early HBV-HCC compared with alpha-fetoprotein (AFP), with an AUC of 0.834 [95% confidence interval (CI), 0.772–0.897] for this panel and 0.727 (95% CI, 0.642–0.812) for AFP (P = 0.0359). In addition, the AUC for this panel to identify AFP-negative patients with HBV-HCC was 0.796 (95% CI, 0.734–0.858), with a sensitivity of 52.4% and a specificity of 89.0%. Importantly, the panel in combination with AFP significantly increased the positive rate for early HBV-HCC to 84.1% (P = 0.005) and for late HBV-HCC to 96.3% (P < 0.001). Our findings suggest that AFP and the autoantibody panel may be independent but complementary serologic biomarkers for HBV-HCC detection. Prevention Relevance: We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection.

Supplementary Table S1: We applied 52 serum samples to the HuProt™ microarray and detected autoantibody signals in 10 pooled HCC samples and 10 pooled normal control (NC) samples, including 30 HCC patients and 22 NCs. Samples were merged based on age and gender to ensure consistency. For the HCC group, ten pooled samples were created by mixing every three sera. As for the NC group, six pooled samples were generated by mixing every three sera, while the remaining four samples were used separately (Supplementary Table S1).

Supplementary Figure S1: In the discovery phase, a total of 71 differentially expressed TAAbs between the HCC and NC groups were identified using HuProt™ microarray (Supplementary Figure S1). These proteins could clearly distinguish the HCC group from the NC group.

Supplementary Table S2: RNA sequencing data (GSE22058, GSE121248, and GSE55092) from the Gene Expression Omnibus (GEO) database were downloaded for analyses. These three datasets derived from two microarray platforms (Rosetta/Merck Human RSTA Custom Affymetrix 1.0 microarray and Affymetrix Human Genome U133 Plus 2.0 Array). The GEO query software package was used to download datasets and to collect clinical information. The sample sizes for these three datasets are shown in Supplementary Table S2.

Supplementary Figure S5: In the training set, the AUC for identifying HBV-HCC patients from CHB patients 0.788 (95% CI: 0.733-0.843) (Supplementary Figure S5A). Similarly, the AUC of the panel was 0.764 (95% CI: 0.695-0.833) in the test-set (Supplementary Figure S5B). In the training set, the AUC for identifying HBV-HCC patients from HBV-LC patients was 0.646 (95% CI: 0.576-0.716) (Supplementary Figure S5C). In the test set, the AUC for identifying HBV-HCC patients from HBV-LC patients was 0.595 (95% CI: 0.507-0.684) (Supplementary Figure S5D).

Supplementary Figure S3: A total of 964 genes were identified by weighted gene co-expression network analysis (WGCNA) and difference analysis (GSE22058, GSE55092 and GSE121248). And four TAAs (ZIC2, PCNA, CDC37L1 and DUSP6) were identified by an intersection of the human proteome microarray and bioinformatics analysis.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that requires precise diagnosis for effective treatment. However, the diagnostic value of carbohydrate antigen 19 − 9 (CA19-9) is limited. Therefore, this study aims to identify novel tumor-associated autoantibodies (TAAbs) for PDAC diagnosis. Methods A three-phase strategy comprising discovery, test, and validation was implemented. HuProt™ Human Proteome Microarray v3.1 was used to screen potential TAAbs in 49 samples. Subsequently, the levels of potential TAAbs were evaluated in 477 samples via enzyme-linked immunosorbent assay (ELISA) in PDAC, benign pancreatic diseases (BPD), and normal control (NC), followed by the construction of a diagnostic model. Results In the discovery phase, protein microarrays identified 167 candidate TAAbs. Based on bioinformatics analysis, fifteen tumor-associated antigens (TAAs) were selected for further validation using ELISA. Ten TAAbs exhibited differentially expressed in PDAC patients in the test phase (P < 0.05), with an area under the curve (AUC) ranging from 0.61 to 0.76. An immunodiagnostic model including three TAAbs (anti-HEXB, anti-TXLNA, anti-SLAMF6) was then developed, demonstrating AUCs of 0.81 (58.0% sensitivity, 86.0% specificity) and 0.78 (55.71% sensitivity, 87.14% specificity) for distinguishing PDAC from NC. Additionally, the model yielded AUCs of 0.80 (58.0% sensitivity, 86.25% specificity) and 0.83 (55.71% sensitivity, 100% specificity) for distinguishing PDAC from BPD in the test and validation phases, respectively. Notably, the combination of the immunodiagnostic model with CA19-9 resulted in an increased positive rate of PDAC to 92.91%. Conclusion The immunodiagnostic model may offer a novel serological detection method for PDAC diagnosis, providing valuable insights into the development of effective diagnostic biomarkers.

Abstract Purpose This meta-analysis aimed to generate a comprehensive overview of relationship between plasma 25-hydroxyvitamin D [25(OH)D] and pancreatic cancer (PC) incidence and mortality. Methods PubMed, Embase and Wed of Science databases were searched through February 15, 2022. A random-effects model was used to estimate total relative risks (RRs) and 95% confidence intervals (CIs). Subgroup, meta-regression, sensitivity and publication bias analyses were employed in this systematic review and meta-analysis. Results After exclusion of ineligible studies, a total of 16 studies that involved 538,673 participants were included in our meta-analysis, of which 10 reported incidence and 6 reported mortality. For the highest versus the lowest plasma 25(OH)D levels, the summary RR of PC incidence was 0.99 (95% CI 0.70–1.29), and the summary RR of PC mortality was 0.78 (95% CI 0.57–0.98). Subgroup analyses showed an inverse association between plasma 25(OH)D and PC incidence in America (RR = 0.70; 95% CI 0.45–0.96) but not in Europe (RR = 1.36; 95% CI 0.86–1.86). Furthermore, plasma 25(OH)D was associated with PC incidence when the duration of follow-up was longer than 10 years (RR = 0.70; 95% CI 0.43–0.97) and when adjusted for race (RR = 0.64; 95% CI 0.35–0.93). The association between plasma 25(OH)D and PC mortality was overall consistent in stratified analyses. Conclusion High plasma 25(OH)D may be associated with the lower PC mortality, but not significantly associated with PC incidence. Our findings may have implications for antitumor therapy in PC patients, as well as caution in increasing vitamin D intake in the general population.

A potential inflammatory biomarker, soluble urokinase‐type plasminogen activator receptor (suPAR) has been utilized to assist the prognostic assessment of coronary artery disease (CAD) patients; however, outcomes have been inconsistent. The prognostic relevance of suPAR as a predictor of CAD patient adverse outcomes was therefore examined.

Background: Reduced DNA repair capacity in nucleotide excision repair (NER) pathways owing to genetic variant may influence cancer susceptibility. According to published studies, variants of NER genes associations with colorectal cancer (CRC) risk were inconclusive. Thus, this meta-analysis aimed to explore the possible association. A trial sequence analysis (TSA) analysis was performed to control the risk of false positive or false negative. Methods: PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Network (CNKI), Wanfang Database and Scientific and Technical Journal Database (VIP) were searched to identify relative studies until April 2022. The association was assessed by odds ratio (OR) in Allele, homozygous, heterozygous, dominant, recessive, and over-dominant models. In addition, Begg's and Egger's tests, sensitivity analysis, subgroup analysis and TSA analysis were performed. Results: A total of 29 studies were eventually included in the meta-analysis, including 12,153 CRC patients and 14,168 controls. It showed that excision and repair cross complementary group 1 (ERCC1) rs11615 CC genotype decreased the risk of CRC, compared with TT genotype (CC vs. TT: OR = 0.816, 95% CI = 0.673-0.990, p = 0.039). For ERCC1 rs3212986, the significant impact was detected on increased the risk of CRC in the allele (OR = 1.267, 95% CI = 1.027-1.562, p = 0.027), homozygous (OR = 1.805, 95% CI = 1.276-2.553, p = 0.001), dominant (OR = 1.214, 95% CI = 1.012-1.455, p = 0.037) and recessive (OR = 1.714, 95% CI = 1.225-2.399, p = 0.002) models, especially in the Asian population. The results revealed the association of ERCC2 rs1799793 A allele with a higher risk of CRC (A vs. G: OR = 1.163, 95% CI = 1.021-1.325, p = 0.023). It also showed that ERCC5 rs17655 increased CRC risk in the allele (OR = 1.104, 95% CI = 1.039-1.173, p = 0.001), homozygous (OR = 1.164, 95% CI = 1.018-1.329, p = 0.026), heterozygous (OR = 1.271, 95% CI = 1.018-1.329, p < 0.001), dominant (OR = 1.241, 95% CI = 1.135-1.358, p < 0.001) and over-dominant (OR = 0.828, 95% CI = 0.762-0.900, p < 0.001) models, especially among Asians. Conclusion: This meta-analysis based on current evidence suggests that the significant association was observed between ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs1799793, and ERCC5 rs17655 and CRC susceptibility. However, given the limited sample size and the influence of genetic background, studies of a larger scale and well-designed are required to confirm the results.

目的:探讨血浆可溶性尿激酶型纤溶酶原激活物受体(suPAR)和损伤严重度评分(ISS)、新损伤严重度评分(NISS)、改良早期预警评分(MEWS)对急诊严重创伤患者病情危重程度的评估价值.方法:纳入2019年12月-2020年10月期间我院急救部抢救室接诊并收住院的严重创伤患者,入院后检测血浆suPAR并完善上述评分,根据入院24 h内的急性生理学和慢性健康状况评分(APACHE)Ⅱ及序贯器官衰竭评分(SOFA)将患者分为危重组和一般组,比较两组患者的一般情况、ISS、NISS、suPAR和MEWS,采用多因素Logistic回归分析患者病情危重的独立预测因子,绘制受试者工作特征(ROC)曲线明确各指标的评估价值.结果:共纳入101例严重创伤患者,其中危重组34例(33.7％),一般组67例(66.3％),危重组患者的血浆suPAR水平、ISS、NISS和MEWS 均显著高于一般组[(6.9±2.7)ng/mL vs.(5.0±2.0)ng/mL,P=0.000;29(26,34)分vs.25(20,29)分,P=0.004;34(34,41)分vs.33(27,34)分,P=0.001;4(3,5)分vs.2(1,3)分,P=0.000],一般情况的组间差异无统计学意义(P＞0.05);多因素Logistic回归分析显示入院时高MEWS、高血浆suPAR水平和高NISS是严重创伤患者病情危重的独立预测因子(OR=2.286,95％CI:1.501～3.482,P=0.000;OR=1.361,95％CI:1.062～1.744,P=0.015;OR=1.102,95％CI:1.014～1.198,P=0.022),ROC 曲线下面积(AUC)分别为0.829(95％CI:0.741～0.896,P＜0.001)、0.721(95％CI:0.623～0.806,P＜0.001)、0.700(95％CI:0.601～0.788,P＜0.001),取截断值＞3分、＞5.02 ng/mL、＞33分时对应的敏感度和特异度分别为70.59％和83.58％、76.47％和61.19％、82.35％和53.73％;suPAR联合MEWS时AUC 为0.857(95％CI:0.774～0.919,P＜0.001),敏感度为73.53％,特异度为86.57％;suPAR联合NISS时AUC 为0.819(95％CI:0.730～0.888,P＜0.001),敏感度为91.18％,特异度为65.67％.结论:单独应用MEWS、血浆suPAR和NISS均能进一步评估严重创伤患者的病情危重程度,suPAR联合MEWS后评估效能最佳,更适用于急诊.

Objective To investigate the predictive value of plasma soluble urokinase-type plasminogen activator receptor (suPAR) for post-severe traumatic multiple organ dysfunction syndrome (MODS). Methods A total of 108 patients suffering from severe trauma admitted to the Trauma Center of our hospital from December 2019 to December 2020 were enrolled. Venous blood samples were collected at admission and plasma suPAR concentration was measured by ELISA, and their demographic and clinical data were collected. The patients were divided into MODS group and non-MODS group according to the sequential organ failure assessment(SOFA) within 14 d after admission. The general data and variables such as suPAR, white blood cell (WBC) count, and injury severity score (ISS) were compared between the 2 groups. Logistic regression analysis was used to screen the independent predictors for post-traumatic MODS, and receiver operating characteristic (ROC) curve was adopted to evaluate the predictive value of the variables. Results Age, rate of comorbidity, ISS, suPAR at admission, rate of shock, rate of infection and rate of surgery were significantly higher in the MODS group than the non-MODS group [52.6±14.1 vs 46.1±14.1 years old, 29.4% vs 9.5%, 29 (25, 33) vs 26 (21, 30) points, 6.7±2.7 vs 5.0±2.1 ng/mL, 41.2% vs 17.6%, 61.8% vs 24.3%, 52.9% vs 32.4%, P < 0.05]. There were no significant differences in sex, injury cause, injury site, WBC count, and rate of blood purification between the 2 groups. Multivariate Logistic regression analysis showed that comorbidity, ISS, suPAR, and infection were independent predictors for post-traumatic MODS (P < 0.05). ROC curve analysis indicated that the area under the curve (AUC) of suPAR for predicting post-traumatic MODS was 0.704 (P < 0.05). When the cutoff value was 5.04 ng/mL, the sensitivity was 73.5% and the specificity was 62.2%. The AUC of ISS was 0.632 (P < 0.05), and the sensitivity was 73.5% and the specificity was 58.1% when the cutoff value was 26. Conclusion The plasma suPAR level at admission can predict the occurrence of post-traumatic MODS in patients with severe trauma. Early monitoring of suPAR has a certain value in evaluation of inflammation and immune activation in the body and in guidance of clinical evaluation and treatment.