Diagnostic Biomarker For Pancreatic Cancer Research Articles

Novel diagnostic biomarkers for pancreatic cancer: assessing methylation status with epigenetic-specific peptide nucleic acid and KRAS mutation in cell-free DNA.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with a poor prognosis that poses challenges for diagnosis using traditional tissue-based techniques. DNA methylation alterations have emerged as potential and promising biomarkers for PDAC. In this study, we aimed to assess the diagnostic potential of a novel DNA methylation assay based on epigenetic-specific peptide nucleic acid (Epi-sPNA) in both tissue and plasma samples for detecting PDAC. The study involved 46 patients with PDAC who underwent surgical resection. Epi-TOP pancreatic assay was used to detect PDAC-specific epigenetic biomarkers. The Epi-sPNA allowed accurate and rapid methylation analysis without bisulfite sample processing. Genomic DNA extracted from paired normal pancreatic and PDAC tissues was used to assess the diagnostic efficacy of epigenetic biomarkers for PDAC. Subsequent validation was conducted on cell-free DNA (cfDNA) extracted from plasma samples, with 10 individuals represented in each group: PDAC, benign pancreatic cystic neoplasm, and healthy control. The combination of seven epigenetic biomarkers (HOXA9, TWIST, WT1, RPRM, BMP3, NPTX2, and BNC1) achieved 93.5% sensitivity and 96.7% specificity in discerning normal pancreatic from PDAC tissues. Plasma cfDNA, analyzed using these markers and KRAS mutations, exhibited a substantial 90.0% sensitivity, 95.0% specificity, and an overall 93.3% accuracy for discriminating PDAC. Notably, cancer antigen 19-9 and carcinoembryonic antigen both had an accuracy of 90.0%. Our study suggests that analyzing seven differentially methylated genes with KRAS mutations in cfDNA using the novel Epi-TOP pancreatic assay is a potential blood-based biomarker for the diagnosis of PDAC.

Unveiling the potential of galectin-3 as a diagnostic biomarker for pancreatic cancer: a review

Early detection of pancreatic cancer is crucial for improving patient outcomes, and identifying reliable biomarkers is a critical research area in this field. Galectin-3 (Gal-3) is a promising candidate for utilisation as a diagnostic biomarker in early-stage pancreatic cancer. This review aims to explore the potential of Gal-3 in pancreatic cancer diagnosis and its implications for precision medicine. Rigorous validation studies are essential to establish the clinical utility of Gal-3, including large-scale investigations to assess its sensitivity, specificity, and predictive value. Combining Gal-3 with existing biomarkers and advanced imaging techniques may enhance the accuracy of early detection. Moreover, Gal-3 holds promise for risk stratification, enabling the identification of high-risk individuals who could benefit from intensified surveillance and early interventions. However, challenges in standardised testing protocols, establishing reference ranges, assay reliability, workflow integration, cost-effectiveness, and healthcare provider education must be addressed for successful implementation. Despite these challenges, Gal-3 presents significant implications for precision medicine in pancreatic cancer management. By unravelling its potential and overcoming the hurdles, Gal-3 could revolutionise early detection, risk stratification, and personalised approaches in pancreatic cancer care. Collaborative efforts and continued research will be crucial in harnessing the full potential of Gal-3 as a diagnostic biomarker for early-stage pancreatic cancer.

83P Evaluation of serum macrophage inhibitory cytokine 1 as a diagnostic biomarker for pancreatic cancer: A systematic review and diagnostic accuracy meta-analysis

83P Evaluation of serum macrophage inhibitory cytokine 1 as a diagnostic biomarker for pancreatic cancer: A systematic review and diagnostic accuracy meta-analysis

The Efficacy of REG Proteins as a Diagnostic Biomarker for Pancreatic Cancer: a Meta-Analysis.

Regenerating gene (REG) family proteins play a pivotal role in cell proliferation, tissue regeneration, and tumor metastasis. Recent studies have concentrated on the role of REG proteins in pancreatic cancer, but the results remain controversial. In this study, a meta-analysis was performed to evaluate the precise diagnostic value of REG proteins in pancreatic cancer. A search was conducted in PubMed, Medline, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Biomedical Literature Database (CBM), and WANFANG Data up to May 5, 2021. The QUADAS-2 tool was used to evaluate the quality of the included studies. The statistical analysis of the diagnostic tests was conducted using RevMan5 and Meta-Disc 1.4. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95% CIs) were calculated from each eligible study. The meta-analysis included 15 articles containing 796 patients and 584 controls. The pooled sensitivity was 0.71 (95% CI: 0.67 - 0.74), the pooled specificity was 0.73 (95% CI: 0.70 - 0.76), and the pooled DOR was 11.35 (95% CI: 5.92 - 21.77), respectively. The overall area under the receiver operating characteristic curve (AUC) was 0.84. Spearman's correlation coefficient was 0.34 (p = 0.221). For the subgroup analysis, the REG4 protein showed higher diagnostic accuracy compared with the other REG proteins. REG proteins have moderate diagnostic accuracy in pancreatic cancer. Further well-designed studies with larger sample sizes and clinical application are needed to validate the results of this meta-analysis.

Vascular invasion and lymph node metastasis mediate the effect of CA242 on prognosis in hilar cholangiocarcinoma patients after radical resection.

Carbohydrate antigen 242 has been clinically used as a diagnostic biomarker for pancreatic cancer. However, the prognostic role of CA242 in hilar cholangiocarcinoma (HCCA) has not been identified. Also, it remains unclear to what extents the vascular invasion and lymph node metastasis mediate the effect of serum CA242 on prognosis. This study aimed to investigate whether vascular invasion and lymph node metastasis mediate the relationship between CA242 levels and clinical prognosis in HCCA patients after radical resection. Data of 234 HCCA patients who accepted radical resection from March 2008 to December 2014 were analyzed. Vascular invasion and lymph node metastasis were assessed by postoperative pathological examinations. Mediation analysis was performed to study the potential causal relationship between CA242 and overall survival (OS) and relapse-free survival (RFS). Survival analysis was performed using the Kaplan-Meier method. Among 234 HCCA patients, 104 patients (44.4%) with normal CA242 levels (≤ 20 IU/ml) had significantly better OS (p=0.004) and RFS (p=0.001) than those 130 patients (55.6%) with elevated CA242 levels (>20 IU/ml). The logistic analysis showed that elevated CA242 was an independent risk factor for vascular invasion (p=0.006) and lymph nodes metastasis (p=0.040). The causal mediation analysis indicated that the vascular invasion (p=0.012 for OS; p=0.036 for RFS) and lymph nodes metastasis (p=0.024 for OS; p=0.014 for RFS) played significant roles in mediating the effect of serum CA242 on OS and RFS. Serum elevated CA242 could be a novel marker for prognosis prediction in HCCA patients. Vascular invasion and lymph node metastasis mediated the relationship between CA242 and clinical prognosis.

Modeling of cancer-related body-wide effects identifies LTB4 as a diagnostic biomarker for pancreatic cancer.

SummaryBackgroundCancer elicits a complex adaptive response in an organism. Limited information is available for the body-wide effects induced by cancer. Here, we evaluated multiorgan changes in mouse models of pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions (pancreatic intraepithelial neoplasia, PanIN) to decipher changes that occur during PDAC development.MethodsRNA-sequencing was employed in the brain, colon, stomach, kidney, heart, liver, and lung tissues of mice with PanIN and PDAC. A combination of differential expression analysis and functional-category enrichment was applied for an in-depth understanding of the multiorgan transcriptome. Differentially expressed genes were verified by quantitative real-time polymerase chain reaction. Neutrophil and macrophage infiltration in multiple organs was analyzed by immunohistochemical staining. Leukotriene B4 (LTB4) levels in mouse and human serum samples were determined by enzyme-linked immunosorbent assay.FindingsTranscriptional changes within diverse organs during PanIN and PDAC stages were identified. Using Gene Ontology enrichment analysis, increased neutrophil infiltration was discovered as a central and prominent affected feature, which occurred in the liver, lung, and stomach at the PanIN stage. The brain appeared to be well protected from the sequels of PanIN or PDAC. Importantly, serum LTB4 was able to discriminate PDAC from normal controls, chronic pancreatitis, and intraductal papillary mucinous neoplasms with high performance.InterpretationOur study provides a high-resolution cartographic view of the dynamic multiorgan transcriptomic landscape of mice with PDAC and its precursor lesions. Our findings suggest that LTB4 could serve as a biomarker for the early detection of PDAC.FundingThe complete list of funders can be found in the Acknowledgement section.

LncRNA GAS8-AS1 is a Novel Prognostic and Diagnostic Biomarker for Pancreatic Cancer.

LncRNA GAS8-AS1 inhibits thyroid carcinoma, but its function in other malignancies is unknown. The present study aimed to investigate the involvement of GAS8-AS1 in pancreatic cancer (PC). The present study included 68 PC patients (38 males and 30 females, 42-66 years, 52.1 ± 4.5) and 62 healthy volunteers (28 males and 24 females, 43-67 years, 52.3 ± 4.9). Real-time quantitative PCR, transient cell transfection, and in vitro cell migration and invasion assays were applied for the research. The study showed that plasma GAS8-AS1 was lower in PC patients than in healthy controls. Downregulation of plasma GAS8-AS1 distinguished early-stage PC patients from healthy controls. Patients with low GAS8-AS1 plasma levels showed a significantly lower 5-year overall survival rate. Plasma miR-1179 levels were also significantly lower in PC patients than in healthy controls and were positively correlated with plasma GAS8-AS1 levels in PC patients but not healthy controls. GAS8-AS1 overexpression upregulated miR-1179, and MiR-1179 overexpression increased GAS8-AS1 level. Overexpression of both GAS8-AS1 and miR-1179 inhibited PC cell migration and invasion. GAS8-AS1 may promote PC by positively interacting with miR-1179.

Diagnostic biomarkers for pancreatic cancer: An update.

Pancreatic ductal adenocarcinoma accounts for the primary type of pancreatic cancer (PC) with a 5-year survival rate of only about 10% in the United States. Early diagnosis will improve chances for curative treatment. To date, a broadly used serum marker for PC diagnosis is carbohydrate antigen 19-9, which is the only approved biomarker currently by the United States Food and Drug Administration. However, it has low specificity; therefore, development of novel biomarkers is urgently needed. Clinical trials are ongoing to evaluate candidate biomarkers for PC diagnosis, and the use of a multi-biomarker panel with current PC diagnostic biomarkers appears promising.

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients.

Simple SummaryEffective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of circulating tumor cells and clusters from the central venous catheter and portal blood. Circulating tumor cells were isolated using an immunomagnetic selection and were detected by microscopy using immunocytochemistry staining. In conclusion, the circulating tumor cell number in portal blood identifies a death risk in patients with early pancreatic cancer.Background. Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). Methods. In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. Results. CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. Conclusions. CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.

IL-6 is associated with expansion of myeloid-derived suppressor cells and enhanced immunosuppression in pancreatic adenocarcinoma patients.

Chronic inflammation favours the expansion of myeloid-derived suppressor cells (MDSCs) by secreting pro-inflammatory mediators. The role of MDSCs in mediating immunosuppression in pancreatic adenocarcinoma and in defining a premalignant route from chronic pancreatitis remains unclear. We aimed to study the immunosuppressive potential of all subsets of MDSCs and their correlation with inflammatory cytokines in pancreatic adenocarcinoma and chronic pancreatitis. Relative frequencies of MDSCs, immunosuppressive markers arginase-1 (ARG-1), programmed death-ligand 1 (PD-L1), reactive oxygen species (ROS) and cytokines in circulation and surgically resected local pancreatic tissue of chronic pancreatitis and pancreatic adenocarcinoma patients were analysed by multicolour flow cytometry and cytokine bead array, respectively. Levels of cytokines involved in MDSCs activation were analysed by ELISA, and the immunosuppressive nature of MDSCs was confirmed by T-cell suppression assay. Frequencies of circulating MDSCs and ARG-1, PD-L1, and ROS were significantly higher in pancreatic adenocarcinoma than healthy controls and showed a significant positive correlation with MDSCs burden in cancer tissue. Serum levels of cytokines IL-6, IL-8 and IL-10 were significantly elevated in pancreatic adenocarcinoma. IL-6 serum levels showed a significant positive correlation with frequencies of circulating MDSCs in pancreatic adenocarcinoma patients, and MDSCs mediated suppression of T-cell proliferation in vitro was associated with elevated IL-6 levels in the cell culture medium. Collectively, our results suggest that IL-6 plays a crucial role in the expansion of MDSCs and activating their immunosuppressive nature in pancreatic adenocarcinoma. The relative frequency of MDSCs in circulation can be used as a potential diagnostic biomarker for pancreatic cancer.

Identification of Serum microRNA-25 as a novel biomarker for pancreatic cancer.

To identify serum microRNA-25 (miR-25) as a diagnostic biomarker for pancreatic cancer (PCa) and to evaluate its supplementary role with serum carbohydrate antigen 19-9 (CA19-9) in early identification of cancers.Eighty patients with pancreatic cancer and 91 non-cancer controls were enrolled in this study. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of miR-25. Levels of CA19-9, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) were measured by chemiluminescent immunoassay. The logistic model was established to evaluate the correlation of miR-25 with clinical characteristics. A risk model for PCa was conducted by R statistical software. Diagnostic utility for PCa and correlation with clinical characteristics were analyzed.The expression level of miR-25, in the PCa group was significantly higher (P < .05). Risk Model illustrated the relation between miR-25 and pancreatic cancer. With the combination of CA19-9, the performance of miR-25 in early stages (I+II) in the diagnosis of PCa was profoundly better than CA19-9 and miR-25 alone. This combination was more effective for discriminating PCa from non-cancer controls (AUC-ROC, 0.985; sensitivity, 97.50%; specificity, 90.11%) compared with CA19-9 alone or the combination of CA19-9 and CA125.The expression level of miR-25 among pancreatic cancer patients was significantly higher than that in the control group. miR-25 existed as one of the most relevant factors of PCa. miR-25 can serve as a novel noninvasive approach for PCa diagnosis, and with the supplementary of CA19-9, the combination was more effective, especially in early tumor screening.

Characterization of Oral Microbiome and Exploration of Potential Biomarkers in Patients with Pancreatic Cancer.

Pancreatic cancer (PC) is highly malignant and lacks an effective therapeutic schedule, hence that early diagnosis is of great importance to achieve a good prognosis. Oral bacteria have been proved to be associated with pancreatic cancer, but the specific mechanism has not been comprehensively illustrated. In our study, thirty-seven saliva samples in total were collected with ten from PC patients, seventeen from benign pancreatic disease (BPD) patients, and ten from healthy controls (HC). The oral bacterial community of HC, PC, and BPD groups was profiled by 16S rDNA high-throughput sequencing and bioinformatic methods. As shown by Simpson, Inverse Simpson, Shannon and Heip, oral microbiome diversity of HC, BPD and PC groups is in increasing order with the BPD and PC groups significantly higher than the HC group. Principal coordinate analysis (PCoA) suggested that grouping by PC, BPD and HC was statistically significant. The linear discriminant analysis effect size (LEfSe) identified high concentrations of Fusobacterium periodonticum and low concentrations of Neisseria mucosa as specific risk factors for PC. Furthermore, predicted functions showed changes such as RNA processing and modification as well as the pathway of NOD-like receptor signaling occurred in both PC and HC groups. Conclusively, our findings have confirmed the destruction of oral bacterial community balance among patients with PC and BPD and indicated the potential of Fusobacterium periodonticum and Neisseria mucosa as diagnostic biomarkers of PC.

Serum Exo-EphA2 as a Potential Diagnostic Biomarker for Pancreatic Cancer

Pancreatic cancer (PC) is a highly malignant tumor with poor detection sensitivity and specificity in biomarkers and diagnosis. Previous research indicated that serum Ephrin type-A receptor 2 in exosomes (Exo-EphA2) was highly expressed and might have facilitated cell migration in PC cells. However, the dynamics of clinical performance of serum Exo-EphA2 in PC patients are unknown. Thus, this study evaluated serum Exo-EphA2 as a potential diagnostic biomarker in PC. The expressions of serum Exo-EphA2 were assessed by enzyme-linked immunosorbent assay for N = 353 serum samples, including from 204 PC patients, 75 patients with benign pancreatic disease, and 74 healthy control patients. Carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 242 (CA 242) were measured by automated immunoassay. Serum Exo-EphA2 levels were significantly higher in PC patients than in benign pancreatic disease and healthy control patients. Receiver operating characteristic curve analysis suggested that using combined diagnoses of Exo-EphA2 with CA 19-9 and CA 242 was more effective to discriminate early stage (stage I and II) in PC than in healthy controls and benign disease patients. Novel findings suggest that serum Exo-EphA2 is a potential early diagnostic biomarker complementing CA 19-9 and CA 242 in PC.

Ligand-targeted polymerase chain reaction for the detection of folate receptor-positive circulating tumour cells as a potential diagnostic biomarker for pancreatic cancer.

ObjectivesTo detect folate receptor (FR)‐positive circulating tumour cells (FR+ CTCs) by using ligand‐targeted polymerase chain reaction (LT‐PCR) in periampullary cancer patients and to investigate the diagnostic value of FR+ CTCs in distinguishing pancreatic cancer (PC) from benign pancreatic disease.Materials and MethodsCTCs were enriched from 3 mL of peripheral blood and portal vein blood by immunomagnetic depletion of leucocytes and were then detected by LT‐PCR. The diagnostic performance of FR+ CTCs in PC was investigated by receiver‐operating characteristic curve analysis.ResultsIn total, 57 consecutive patients, including 46 patients with PC, five patients with non‐pancreatic periampullary cancer (non‐PC) and six patients with benign pancreatic diseases, were enrolled. FR+ CTC levels were significantly higher in patients with malignant diseases (PC and non‐PC) than in patients with benign pancreatic diseases (P < .01). There was no notable difference in CTC levels between patients with PC and those with non‐PC (P > .05). The combination of FR+ CTCs with carbohydrate antigen 19‐9 (CA19‐9) had better diagnostic efficiency than each of these two markers alone, with high sensitivity (97.8%) and specificity (83.3%).ConclusionsLT‐PCR is feasible and reliable for detecting FR+ CTCs in patients with periampullary cancer. FR+ CTCs, especially when used in combination with CA19‐9, have potential as a biomarker for the diagnosis of PC.

MIR1246 in body fluids as a biomarker for pancreatic cancer

Pancreatic cancer is an aggressive tumor associated with poor survival, and early detection is important to improve patient outcomes. In the present study, we examined MIR1246 expression as a biomarker of pancreatic cancer. Total RNA was extracted from serum, urine and saliva samples from healthy subjects (n = 30) and patients with pancreatic cancer (n = 41, stage 0–IV). The MIR1246 level in each fluid was analyzed by quantitative reverse transcription-polymerase chain reaction. Significantly higher MIR1246 expression in serum and urine was observed in patients with cancer than in healthy controls. A significant positive correlation was found between serum and urine MIR1246 expression (r = 0.34). Receiver operating characteristic curves were constructed for MIR1246 in all three body fluids. The area under the curve for serum MIR1246 was 0.87 (sensitivity, 92.3%; specificity, 73.3%), and that for urine MIR1246 was 0.90 (sensitivity, 90.2%; specificity, 83.3%). With a cut-off of the control group’s mean plus twice the standard deviation, the sensitivities of MIR1246 in serum and urine for pancreatic cancer were 60.9 and 58.5%, respectively. Combining both serum and urine MIR1246 expression yielded a sensitivity of 85%. These results indicate that MIR246 may be a useful diagnostic biomarker for pancreatic cancer.

Circulating microRNAs as promising diagnostic biomarkers for pancreatic cancer: a systematic review.

Pancreatic cancer (PC) is one of the most common forms of malignant tumors and causes of tumor-related death worldwide. The current prognosis of PC still remains poor due to the lack of effective early detection method. Recently, there is strong support that circulating miRNAs can be used as biomarkers for early detection of various cancers, including PC. The purpose of this review is to provide an overview of previous published studies on circulating miRNAs in plasma/serum for early detection of PC and summarize their diagnostic value. PubMed, Embase and Web of Science were systematically searched for eligible studies on circulating miRNAs for PC detection. Overall, 29 studies published between 2009 and 2018 evaluating 51 individual miRNAs (no P-value exceeding 0.05) and 13 miRNAs panels were included. Generally, the diagnostic performance of circulating miRNAs for PC detection was strong, with both the sensitivity and specificity of 36% individual miRNAs and 40% miRNAs panels exceeding 80%. Moreover, two promising miRNA panels were discovered and verified externally with all AUC values exceeding 0.95. Therefore, circulating miRNAs may hold potential to be used as noninvasive diagnostic biomarkers for PC, but large-scale studies are still needed to validate the promising miRNAs and optimize the miRNA panels. Since, the tremendous heterogeneity of studies in this field hampers translating miRNA markers into clinical practice, miRNA analytical procedures are also needed to be standardized in the future.

Diagnostic yield of the plasma free amino acid index for pancreatic cancer in patients with diabetes mellitus

ObjectivesA multivariate index calculated using plasma free amino acids (PFAA index) was reported as a diagnostic biomarker for pancreatic cancer (PaC). Although diabetes mellitus (DM) is expected to be an early diagnostic indicator of PaC, identifying the high-risk individuals among patients with DM is warranted. We evaluated the diagnostic yield of the PFAA index for PaC in patients with DM. MethodsWe compared the diagnostic yield of the PFAA index between individuals with and those without DM. Cases and controls were recruited prospectively, and controls were matched to cases at a 1:1 ratio for age, sex, and DM status. ResultsA total of 180 case–control pairs were included in the analysis. The prevalence of DM was 53.3%. The sensitivity of the PFAA index was 66.7% in cases with DM and 56.0% in those without DM (P = 0.14), and the specificity was 92.7% in controls with DM and 94.0% in those without DM (P = 0.95). ConclusionsThis matched case-control study revealed a comparable diagnostic yield of the PFAA index for PaC in individuals with and those without DM. The PFAA index can be used as a biomarker for further diagnostic imaging in selected patients with DM.

Exosomal zinc transporter ZIP4 promotes cancer growth and is a novel diagnostic biomarker for pancreatic cancer.

Pancreatic cancer is one of the deadliest cancers with rapid disease progression. Further elucidation of its underlying molecular mechanisms and novel biomarkers for early detection is necessary. Exosomes are small extracellular vesicles that are released by multiple cell types acting as message carriers during intercellular communication and are promising biomarker candidates. However, the role of pancreatic cancer cell‐derived exosomes in cancer progression and the application of these vesicles as novel diagnostic biomarkers have not been fully studied. In this study, we found that PC‐1.0 (a highly malignant pancreatic cell line) cell‐derived exosomes could be taken up by and enhance PC‐1 (a moderately malignant pancreatic cell line) cell proliferation, migration and invasion abilities. We identified ZIP4 as the most upregulated exosomal protein in PC‐1.0 cells from our proteomic analysis. In vitro and in vivo (a subcutaneous BALB/c nude mouse model) studies showed that exosomal ZIP4 can significantly promote pancreatic cancer growth. Using clinical blood samples, we compared the diagnostic values of serum exosomal ZIP4 levels between malignant pancreatic cancer patients (n = 24) and benign pancreatic disease patients (n = 32, AUC = .89), and between biliary disease patients (n = 32, AUC = .8112) and healthy controls (n = 46, AUC = .8931). In conclusion, exosomal ZIP4 promotes cancer growth and is a novel diagnostic biomarker for pancreatic cancer.

Heterogeneous Expression of Embryonal Development Master Regulator SOX9 in Patients with Pancreatic Cancer.

The expression levels of the SOX9 gene in fetal, postnatal, and neoplastic pancreatic tissues were compared. In the fetal pancreatic samples, the mean relative level of the SOX9 gene expression was 8 times greater than the normal level. The tumor samples were divided into three groups depending on the SOX9 expression level. The first group showed a 6.5-fold increased expression level of SOX9 with respect to the normal one. The second and normal groups had approximately equal levels expression. The third group showed a 25-fold decreased expression level of SOX9. The discrepancy in the SOX9 expression, associated with the predominance of different functions of this master gene, depends on the poorly predictable individual factors and indicates that SOX9 should be excluded from the potential diagnostic biomarkers of pancreatic cancer.

Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence from comprehensive miRNA expression profiling analysis and clinical validation

Pancreatic cancer (PC) is a highly fatal disease worldwide and is often misdiagnosed in its early stages. The exploration of novel non-invasive biomarkers will definitely benefit PC patients. Recently, circulating miRNAs in body fluids are emerging as non-invasive biomarkers for PC diagnosis. In this study, we first conducted comprehensive robust rank aggregation (RRA) analysis based on 21 published miRome profiling studies. We statistically identified and clinically validated a miRNA expression pattern in PC patients. These miRNAs consisted of four up-regulated (hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-210-3p and hsa-miR-155-5p) and three down-regulated miRNAs (hsa-miR-217, hsa-miR-148a-3p and hsa-miR-375). Among them, hsa-miR-21-5p was one of the most highly expressed miRNAs in the serum of PC patients. Our validation test further suggested a relatively high accuracy of serum hsa-miR-21-5p levels in the diagnosis of PC, with a sensitivity of 0.77 and a specificity of 0.80. Finally, a diagnostic meta-analysis based on 9 studies also revealed favorable sensitivity and specificity of circulating hsa-miR-21-5p for the diagnosis of PC (pooled sensitivity and specificity were 0.76 and 0.74, respectively), which was consistent with our findings. Taken together, as one of the most aberrantly expressed miRNAs in PC, circulating hsa-miR-21-5p might be a promising serum biomarker in patients with PC.