Pancreatic cancer accounts for 2.8% of new cancer cases worldwide and is projected to become the second leading cause of cancer-related deaths by 2030. Patients of African ancestry appear to be at an increased risk for pancreatic ductal adenocarcinoma (PDAC), with more severe disease and outcomes. The purpose of this study was to map the proteomic and genomic landscape of a cohort of PDAC patients of African ancestry. Thirty tissues (15 tumours and 15 normal adjacent tissues) were obtained from consenting South African PDAC patients. Optimisation of the sample preparation method allowed for the simultaneous extraction of high-purity protein and DNA for SWATH-MS and OncoArray SNV analyses. We quantified 3402 proteins with 49 upregulated and 35 downregulated proteins at a minimum 2.1 fold change and FDR adjusted p-value (q-value) ≤ 0.01 when comparing tumour to normal adjacent tissue. Many of the upregulated proteins in the tumour samples are involved in extracellular matrix formation (ECM) and related intracellular pathways. In addition, proteins such as EMIL1, KBTB2, and ZCCHV involved in the regulation of ECM proteins were observed to be dysregulated in pancreatic tumours. Downregulation of pathways involved in oxygen and carbon dioxide transport were observed. Genotype data showed missense mutations in some upregulated proteins, such as MYPN, ESTY2 and SERPINB8. Approximately 11% of the dysregulated proteins, including ISLR, BP1, PTK7 and OLFL3, were predicted to be secretory proteins. These findings help in further elucidating the biology of PDAC and may aid in identifying future plausible markers for the disease.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type characterized by dysregulated cell signalling pathways and resistance to treatment. The insulin‑like growth factor (IGF) signalling pathway has been identified to have a role in tumour progression and therapy resistance. However, its regulatory roles in PDAC have remained to be fully elucidated. In the present study, dysregulated microRNAs (miRNAs) in PDAC were explored with a focus on those that may be involved in regulating the insulin/IGF signalling pathway. A total of 208 patients were recruited, comprising 112 patients with PDAC, 50 patients with chronic pancreatitis (CP) and 46 subjects as a control group (CG). miRNA‑specific quantitative PCR assays were used to measure 300 candidate miRNAs. The Student's t‑test was applied to compare miRNA regulation between cancer patients and controls with a false discovery rate correction using Bonferroni‑type comparison procedures. The DIANA‑mirPath v.3 tool and HMDD v3.0 were used to identify miRNA‑mRNA interactions within specific pathways. In patients with PDAC, 42 miRNAs were significantly upregulated and 42 were downregulated compared to the CG (P<0.01). In the PDAC vs. CP analysis, 16 significantly (P<0.01) upregulated and 16 downregulated miRNAs were identified. Of note, members of the let‑7 family of miRNAs were downregulated and were indicated to target several components of the insulin receptor (INSR)/IGF pathway, including receptors and binding proteins, for upregulation and thus, may enable the activation of the pathway. Downregulation of the let‑7 family may help promote the INSR/IGF pathway in PDAC. It may thus be an effective target for the development of INSR/IGF pathway‑specific treatment strategies.

Pancreatic cancer is an aggressive cancer, making it a leading cause of cancer‑related deaths. It is characteristically resistant to treatment, which results in low survival rates. In pancreatic cancer, immune cells undergo transitions that can inhibit or promote their functions, enabling treatment resistance and tumor progression. These transitions can be fostered by metabolic pathways that are dysregulated during tumorigenesis. The present review aimed to summarize the different immune cells and their roles in pancreatic cancer. The review also highlighted the individual metabolic pathways in pancreatic cancer and how they enable transitions in immune cells. Finally, the potential of targeting metabolic pathways for effective therapeutic strategies was considered.

Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance. Here we review the role of the individual growth factors in pancreatic cancer chemoresistance. Importantly, the interplay between the tumor microenvironment and chemoresistance is explored in the context of pivotal role played by growth factors. We further describe current and future potential therapeutic targeting of these factors.

Background: Gallbladder cancer (GBC) is a lethal cancer with a poor prognosis. The lack of specific and sensitive biomarkers results in delayed diagnosis with most patients presenting at late stages of the disease. Furthermore, there is little known about the molecular mechanisms associated with GBC, especially in patients of African ancestry. This study aimed to determine dysregulated proteins in South African GBC patients to identify potential mechanisms of the disease progression and plausible biomarkers. Methods: Tissues (27 GBC, 13 Gallstone disease, and 5 normal tissues) and blood plasma (54 GBC and 73 Benign biliary pathology) were obtained from consenting patients. Protein extraction was performed on all tissues and liquid chromatography-mass spectrometry was used for proteomic profiling. A project-specific spectral library was built using the Pulsar search algorithm. Principal component and Spearman’s rank correlation analyses were performed using PAST (V4.07b). Pathway and Network analyses were conducted using REACTOME (v3.7) and stringAPP (v1.7.0), respectively. Results: In the tissue sample group, there were 62 and 194 dysregulated proteins in GBC compared to normal and gallstone groups, respectively. In the plasma group, there were 33 altered proteins in GBC compared to the benign biliary pathology group. We found 9 proteins (APOA1, APOA2, RET4, TTR, HEMO, HBB, HBA, PIGR, and APOE) to be commonly dysregulated in both tissue and plasma. Furthermore, a subset analysis demonstrated that 2 proteins, S100A8 and S100A9, were downregulated in GBC patients with GD history compared to those without. Pathway analysis showed that the dysregulated proteins in GBC patients were enriched in pathways involved in smooth muscle contraction, metabolism, ECM organization, and integrin cell surface interactions. Conclusion: The identified dysregulated proteins help in understanding GBC molecular mechanisms in our patient group. Furthermore, the alteration of specific proteins in both tissue and plasma samples suggests their potential utility as biomarkers of GBC in this sample cohort.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.