Differential gene expression analysis of peripheral blood mononuclear cells reveals novel test for early detection of pancreatic cancer

Abstract

Background We sought to validate global microarray results indicating the differential expression of 383 genes in Peripheral Blood Mononuclear Cells (PBMCs) from patients with pancreatic cancer (PC) and to further evaluate their PC diagnostic potential. Methods and materials In total, 177 patients were recruited (47 healthy controls (HC), 35 CP patients, and 95 PC patients). PBMC expressions of six genes from our previous study (ANXA3, ARG1, CA5B, F5, SSBP2, and TBC1D8) along with four new genes (MIC1, NGAL, MUC1, and MUC16) were analyzed using multiplex Q-RT PCR. Results Differential expressions of 5 of the 6 genes previously identified by PBMC microarray were validated in this study. Multivariate models for PBMC gene expression were attempted to determine if any combination was diagnostically superior to CA19-9 alone. We found that addition of PBMC CA5B, F5, SSBP2, and MIC1 expression levels to CA19-9 significantly improved CA19-9’s diagnostic abilities when comparing resectable PC to CP patients (p = 0.023). Conclusions Results of our previous study were validated, indicating reproducibility of PC-associated PBMC expression profiling. We identified a score-based model that can differentiate resectable PC from CP better than CA19-9, potentiating that PBMC differential expression analysis may offer a novel tool for early PC diagnosis.

Early Diagnosis of Pancreatic Cancer: Challenges and New Developments

“…The diagnostic efficacy of these, along with four new genes ( MIC1 , NGAL , MUC1 and MUC16 ), were further validated in 47 healthy controls, 35 CP patients and 95 PC patients using multiplex quantitative real-time PCR. The combination of CA5B, F5, SSBP2 and MIC1 expression levels with CA19.9 significantly improved all aspects of early PC diagnosis for differentiating CP, providing a 2% increase in sensitivity (67 vs 65%) and a 3% increase in specificity (83 vs 80%) over CA19.9 alone [52]. Although considerable improvements were not observed over the sensitivity and specificity of CA19.9, these studies signify the utility of PBMCs in early diagnosis.…”

Transcriptional Profiling of Peripheral Blood in Pancreatic Adenocarcinoma Patients Identifies Diagnostic Biomarkers

“…The fold change in gene expression was determined by the 2 -DDCt method using the same control RNA as that employed in the microarray. The median fold change in expression between PDAC patients and healthy controls was calculated for each gene and compared with the microarray result this panel was found to be superior to CA 19-9 for distinguishing between resectable PC and chronic pancreatitis [27]. A recent comparison of PBMCs between PDAC patients and healthy controls found that RT-qPCR determined olfactomedin 4 expression may be a prognostic marker for this cancer, although the study sample was small (5 patients and controls), and the values obtained by microarray technology (4.46) and RT-qPCR (4.80) were somewhat different [28].…”

Identification of dissociation factors in pancreatic Cancer using a mass spectrometry-based proteomic approach

“…CPN1 can prevent the accumulation of polypeptides and regulate the secretory hormone level [21]. Baine MJ et al reported that the level of coagulation factor V was found to be significantly different in an analysis of peripheral monocytes from pancreatic cancer patients and might be related to tumor stage [22]. YWHAG is a member of a highly conserved family of proteins that participates in many intracellular signal transduction processes and plays an important role in cell survival and proliferation [23][24][25][26].…”