Transcriptional Profiling of Peripheral Blood Mononuclear Cells in Pancreatic Cancer Patients Identifies Novel Genes with Potential Diagnostic Utility

Abstract

BackgroundIt is well known that many malignancies, including pancreatic cancer (PC), possess the ability to evade the immune system by indirectly downregulating the mononuclear cell machinery necessary to launch an effective immune response. This knowledge, in conjunction with the fact that the trancriptome of peripheral blood mononuclear cells has been shown to be altered in the context of many diseases, including renal cell carcinoma, lead us to study if any such alteration in gene expression exists in PC as it may have diagnostic utility.Methods and FindingsPBMC samples from 26 PC patients and 33 matched healthy controls were analyzed by whole genome cDNA microarray. Three hundred eighty-three genes were found to be significantly different between PC and healthy controls, with 65 having at least a 1.5 fold change in expression. Pathway analysis revealed that many of these genes fell into pathways responsible for hematopoietic differentiation, cytokine signaling, and natural killer (NK) cell and CD8+ T-cell cytotoxic response. Unsupervised hierarchical clustering analysis identified an eight-gene predictor set, consisting of SSBP2, Ube2b-rs1, CA5B, F5, TBC1D8, ANXA3, ARG1, and ADAMTS20, that could distinguish PC patients from healthy controls with an accuracy of 79% in a blinded subset of samples from treatment naïve patients, giving a sensitivity of 83% and a specificity of 75%.ConclusionsIn summary, we report the first in-depth comparison of global gene expression profiles of PBMCs between PC patients and healthy controls. We have also identified a gene predictor set that can potentially be developed further for use in diagnostic algorithms in PC. Future directions of this research should include analysis of PBMC expression profiles in patients with chronic pancreatitis as well as increasing the number of early-stage patients to assess the utility of PBMCs in the early diagnosis of PC.

Combined Serum CA19-9 and miR-27a-3p in Peripheral Blood Mononuclear Cells to Diagnose Pancreatic Cancer

“…Furthermore, CD4þ T cells derived from miR-17-92 transgenic mice exhibit an enhanced type-1 phenotype associated with increased interferon-g production and very late antigen (VLA)-4 expression. Baine and colleagues (17) reported the first in-depth comparison between global gene expression profiles of PBMCs from pancreatic cancer patients and healthy controls. Those authors identified a gene predictor set that could potentially be further developed for use in diagnostic algorithms for pancreatic cancer.…”

“…Based on this idea, it would be useful to study the role of microRNAs in peripheral blood mononuclear cells (PBMCs) in the context of diagnosis and prognosis of malignant tumors. Several studies have identified transcripts expressed differentially between PBMCs from cancer patients and normal subjects, and some of these expression changes seem to reflect specific immune responses of circulating cells (16,17). However, few studies have been done on PBMC microRNAs, which could be of use as diagnostic biomarkers for pancreatic cancer.…”

Changes of the Expressions of Orphan and gon- ADAMTS in Chondrosarcoma Cells

“…41 In our study, ADAMTS20 has increased just after insulin application, but after that, it has decreased in day 3 and protected its low level throughout the study interval. Baine et al 45 showed that ADAMTS20 could distinguish pancreatic cancer patients from healthy controls and ADAMTS20 may be potential diagnostic marker in pancreas cancers. In the present study, ADAMTS20 was found to be decreased gradually in chondrosarcoma cell line.…”

Impact of Annexin A3 expression in gastric cancer cells

“…Human Annexin A3 genes are dispersed throughout the genome on chromosomes 4 q13-q22, including the two main isoforms of 33 kD and 36 kD [20]. Many studies have shown that changes in Annexin A3 expression have an important impact on the onset, development, drug resistance, and metastasis of tumors [12][13][14][15][16][17][18]26]. The expression of Annexin A3 in carcinoma tissues is also closely associated with cancer type.…”

“…Annexin A3 may act as a tumor suppressor or tumor promoter depending upon the type of tumor cell and tissue. Annexin A3 has been shown to be upregulated [13] in prostate cancer, and downregulated in kidney and thyroid cancers [14,15]. Increased expression of Annexin A3 enhanced the drug resistance of ovarian and liver cancers [16,19], promoted the progression of pancreatic, rectal, and glandular cancers [17], and accelerated the metastasis of lung cancer [18].…”