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

Article type: Research Article

Authors: Baine, Michael J.^{a; 1} | Menning, Melanie^{b; 1} | Smith, Lynette M.^c | Mallya, Kavita^b | Kaur, Sukhwinder^b | Rachagani, Satyanarayana^b | Chakraborty, Subhankar^b | Sasson, Aaron R.^d | Brand, Randall E.^e | Batra, Surinder K.^{a; b; *}

Affiliations: [a] Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center Omaha, NE, USA | [b] Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA | [c] Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA | [d] Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA | [e] Division of Gastroenterology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Correspondence: [*] Corresponding author: Surinder K. Batra, Ph.D., Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-5870, USA. Tel.: +1 402 559 5455; Fax: +1 402 559 6650; E-mail: [email protected].

Note: [1] These authors contributed equally to the work.

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 chronic pancreatitis (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.

Keywords: Pancreatic cancer, chronic pancreatitis, PBMC, CA19-9, diagnosis

DOI: 10.3233/CBM-2012-0260

Journal: Cancer Biomarkers, vol. 11, no. 1, pp. 1-14, 2012