Pancreatic ductal adenocarcinoma: Prognostic indicators of advanced disease

Abstract

Background/Objectives Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with high metastatic risk. Prognosis remains poor even after resection. Previously our group identified biomarkers that improved diagnostic accuracy in PDAC beyond the established diagnostic tumour marker, CA19-9. Risk factors, symptoms and circulating biomarkers associated with a PDAC diagnosis may differ from those that alter disease progression and metastasis. This study aimed at assessing the risk factors, presenting symptoms and potential prognostic biomarkers in PDAC and determine their relationship with PDAC stage and/or metastatic status. Methods Seventy-two PDAC patients with imaging available for TNM staging at presentation were enrolled following informed consent. Demographic and clinical data were captured. Blood was collected and 38 cytokines/angiogenic factors measured. Nonparametric association tests, univariate and multivariate logistic regression were performed using STATA version 14.2. A p-value≤0.05 was considered significant and odds ratios reported for effect size. Results Most risk factors and symptoms did not differ across the stages of cancer. Although male gender and smoking are risk factors for PDAC, the majority of study patients with metastatic PDAC were non-smoking females. In addition to CA19-9, the platelet count (p<0.01), IL-15 (p = 0.02) and GM-CSF (p<0.01) were significant, independent negative predictors of metastatic PDAC. Moreover, using specific cut-off values in a combined panel, the odds in a patient with all three biomarker levels below the cut-offs is 21 times more likely to have metastatic PDAC (p<0.0001). Conclusions Platelet count, IL-15 and GM-CSF are potential prognostic indicators of metastatic disease in PDAC patients from our local South African population.

Tumor Stroma Area and Other Prognostic Factors in Pancreatic Ductal Adenocarcinoma Patients Submitted to Surgery

“…According to this, the potential beneficial role of metformin has been studied [43], but we did not obtain significant results for its effect on OS. Despite our results for AHT and DM, no significant difference was seen in AHT and DM rates across PDAC stages in the literature [41].…”

“…A metanalysis did not observe a statistically significant association between AHT and pancreatic cancer [40]. On the other hand, the association between DM and PDAC has been reported, the prevalence of PDAC is higher in adults with new-onset DM than in the general population [41], and patients with this comorbidity have higher mortality overall [42]. According to this, the potential beneficial role of metformin has been studied [43], but we did not obtain significant results for its effect on OS.…”

Influences of calorie restriction and lipopolysaccharide therapy on inflammation, cytokine response, and cell proliferation in pancreatic adenocarcinoma mouse model

“…[ 43 ] In a study of 131 South African PDAC and benign control patients, IFN‐γ, IL‐4, IL‐5, IL‐15, and IL‐17 levels decreased in the PDAC group, whereas IL‐8, CXCL10 (IP‐10), and MIP‐1β levels increased, but the levels of IL‐2, IL‐6, IL‐7, IL‐9, IL‐10, IL‐12, IL‐13, IL‐21, IL‐22, and IL‐23 were similar in both groups. [ 44 ] Studies show that circulating inflammatory cytokine levels are still controversial in PDAC patients. In our study, we found that plasma IL‐5 and TNF‐α levels of the PDAC + LPS group decreased compared to the LPS group, whereas the IL‐10 level increased.…”

Advancements in Preclinical Models of Pancreatic Cancer

“…Pancreatic ductal adenocarcinoma is seldom detected at an early stage. The lag in detection is due to late clinical expression and the nonspecificity of symptoms like jaundice, abdominal pain, and oily stools 15,16 . This means patients are also considered for alternative diagnoses during medical needs, increasing the treatment response time needed.…”

“…The lag in detection is due to late clinical expression and the nonspecificity of symptoms like jaundice, abdominal pain, and oily stools. 15,16 This means patients are also considered for alternative diagnoses during medical needs, increasing the treatment response time needed. Another reason for the late detection of PDAC is the lack of effective screening strategies and biomarkers to reliably detect early-stage PDAC or its precursor lesions.…”