Unraveling pancreatic ductal adenocarcinoma immune prognostic signature through a naive B cell gene set.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), a leading cause of cancer mortality, has a complex pathogenesis involving various immune cells, including B cells and their subpopulations. Despite emerging research on the role of these cells within the tumor microenvironment (TME), the detailed molecular interactions with tumor-infiltrating immune cells (TIICs) are not fully understood. METHODS: We applied CIBERSORT to quantify TIICs and naive B cells, which are prognostic for PDAC. Marker genes from scRNA-seq and modular genes from weighted gene co-expression network analysis (WGCNA) were integrated to identify naive B cell-related genes. A prognostic signature was constructed utilizing ten machine-learning algorithms, with validation in external cohorts. We further assessed the immune cell diversity, ESTIMATE scores, and immune checkpoint genes (ICGs) between patient groups stratified by risk to clarify the immune landscape in PDAC. RESULTS: Our analysis identified 994 naive B cell-related genes across single-cell and bulk transcriptomes, with 247 linked to overall survival. We developed a 12-gene prognostic signature using Lasso and plsRcox algorithms, which was confirmed by 10-fold cross-validation and showed robust predictive power in training and real-world cohorts. Notably, we observed substantial differences in immune infiltration between patients with high and low risk. CONCLUSION: Our study presents a robust prognostic signature that effectively maps the complex immune interactions in PDAC, emphasizing the critical function of naive B cells and suggesting new avenues for immunotherapeutic interventions. This signature has potential clinical applications in personalizing PDAC treatment, enhancing the understanding of immune dynamics, and guiding immunotherapy strategies.

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.

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 review is 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.

CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients.

Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly cancer. Although characterized by 5-20% of neoplastic cells in the highly fibrotic stroma, immunotherapy is not a valid option in PDAC treatment. As CXCR4-CXCL12 regulates tumor invasion and T-cell access and PD-1/PD-L1 controls immune tolerance, 76 PDACs were evaluated for CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in the epithelial and stromal component. Neoplastic CXCR4 and CXCL12 discriminated PDACs for recurrence-free survival (RFS), while CXCL12 and CXCR7 discriminated patients for cancer-specific survival (CSS). Interestingly, among patients with radical resection (R0), high tumor CXCR4 clustered patients with worse RFS, high CXCL12 identified poor prognostic patients for both RFS and CSS, while stromal lymphocytic-monocytic PD-L1 associated with improved RFS and CSS. PD-1 was only sporadically expressed (<1%) in focal lymphocyte infiltrate and does not impact prognosis. In multivariate analysis, tumoral CXCL12, perineural invasion, and AJCC lymph node status were independent prognostic factors for RFS; tumoral CXCL12, AJCC Stage, and vascular invasion were independent prognostic factors for CSS. CXCL12's poor prognostic meaning was confirmed in an additional perspective-independent 13 fine-needle aspiration cytology advanced stage-PDACs. Thus, CXCR4-CXCL12 evaluation in PDAC identifies prognostic categories and could orient therapeutic approaches.

Association of Neutrophil, Platelet, and Lymphocyte Ratios with the Prognosis in Unresectable and Metastatic Pancreatic Cancer.

We examined the relationship between the daily rate of change of cancer antigen 19-9 (CA19-9) over the first 90 days of treatment (DRC90) and the pretreatment levels of neutrophils, lymphocytes, and platelets with the overall survival (OS) and progression-free survival (PFS) in patients with stage IV pancreatic ductal adenocarcinoma (PDA) who received chemotherapy. We retrospectively evaluated 102 locally advanced and metastatic PDA patients treated at the University of Kansas Cancer Center (KUCC) between January 2011 and September 2019. We compared the ratio of the pretreatment absolute neutrophil count to the pretreatment absolute lymphocyte count (NLR) and the ratio between the pretreatment platelet count to the pretreatment absolute lymphocyte count (PLR) with the OS and PFS. We compared the DRC90 to the OS and PFS. The ratios were analyzed using the log-rank trend test using the mean of the NLR, PLR, and DRC90 as the threshold for two groups within each variable. Patients with ≥mean NLR (4.6 K/µL) had a significantly lower OS (p = 0.0444) and PFS (p = 0.0483) compared with patients below the mean. Patients with PLR ≥ mean (3.9 K/µL) did not have a significantly different OS (p = 0.507) or PFS (p = 0.643) compared with patients below the mean. Patients with DRC90 ≥ mean (-1%) did not have a significantly different OS (p = 0.342) or PFS (p = 0.313) compared with patients below the mean. Patients with NLR ≥ mean (4.6 K/µL) had a significantly lower OS and PFS compared with patients with NLR below the mean. This implies the possibility of NLR as a prognostic marker in PDA that could guide treatment approaches but still requires validation in a larger cohort.

Meta-analysis of Modified FOLFIRINOX Regimens for Patients With Metastatic Pancreatic Cancer.

BACKGROUND: We performed a meta-analysis of previous reports evaluating the effect of mFIO (modified FOLFIRINOX; leucovorin, 5-fluorouracil, irinotecan, oxaliplatin) regimens in advanced pancreatic cancer. MATERIALS AND METHODS: We performed a meta-analysis of reported studies in PubMed, Scopus, and Web of Science (1950-2016) in December 2016. The inclusion criteria were randomized trials, prospective or retrospective cohorts, patients with metastatic pancreatic adenocarcinoma, the use of mFIO or FOLFIRINOX (FIO) chemotherapy, and available information for ≥ 1 efficacy endpoint (response rate, progression-free survival, and/or overall survival). The outcomes were compared according to the chemotherapy regimen using a random effects model. We also performed a meta-regression analysis to evaluate the effect of dose reductions on outcomes. RESULTS: Of 2525 abstracts, 32 were considered eligible. Modifications in the FIO regimen included omission of the 5-fluorouracil bolus and/or dose reductions in infusional 5-fluorouracil, irinotecan, and/or oxaliplatin. mFIO was not associated with inferior response rates (32% vs. 33%; P = .879), lower rates of survival at 11 months (47% vs. 50%; P = .38), or lower 6-month progression-free survival rates (47% vs. 53%; P = .38). The meta-regression of the percentage of dose reduction failed to show any association. CONCLUSION: The results of the present meta-analysis with a combined sample size of 1461 patients suggest that it is reasonable to consider mFIO regimens for patients with metastatic pancreatic adenocarcinoma.