Establishment of Biomarker Panel May Lead to Rapid Tests for Early Diagnosis of Pancreatic Cancer

Investigators at Beth Israel Deaconess Medical Center (Boston, MA, USA) applied innovative data normalization and gene selection approaches to analyze a number of publicly available pancreatic cancer gene expression datasets. They combined the statistical power of multiple genomic studies while masking their variability and batch effects to identify robust early diagnostic biomarkers of pancreatic cancer.

The investigators established a panel comprising the genes TMPRSS4 (Transmembrane protease, serine 4), AHNAK2 (AHNAK nucleoprotein 2), POSTN (Periostin), ECT2 (Epithelial cell transforming 2), and SERPINB5 (Serpin peptidase inhibitor, clade B (ovalbumin), member 5) that achieved on average 95% sensitivity and 89% specificity in discriminating pancreatic ductal adenocarcinoma (PDAC) from non-tumor samples in four training sets and similar performance in five independent validation datasets. The five-gene classifier accurately discriminated PDAC from chronic pancreatitis, other cancers, and non-tumor samples from PDAC precursors in three independent datasets.

PDAC-specific expression of the biomarker panel was measured by qRT-PCR (qualitative real-time PCR) in microdissected patient-derived FFPE (formalin-fixed, paraffin-embedded) tissues. Cell-based assays were then used to assess the impact of two of the biomarkers, TMPRSS4 and ECT2, on PDAC cells.

Results revealed that knock-down of TMPRSS4 and ECT2 reduced PDAC soft agar growth and cell viability, and TMPRSS4 knockdown also blocked PDAC migration and invasion.

“Pancreatic cancer is a devastating disease with a death rate close to the incidence rate,” said senior author Dr. Towia Libermann, professor of medicine at Beth Israel Deaconess Medical Center. “Because more than 90% of pancreatic cancer cases are diagnosed at the metastatic stage, when there are only limited therapeutic options, earlier diagnosis is anticipated to have a major impact on extending life expectancy for patients. There has been a lack of reliable markers, early indicators, and risk factors associated with pancreatic cancer, but this new way of differentiating between healthy and malignant tissue offers hope for earlier diagnosis and treatment.”

“Because these five genes are turned on so early in the development of pancreatic cancer, they may play roles as drivers of this disease and may be exciting targets for therapies,” said Dr. Libermann. “Moving forward, we will explore the potential to convert this tissue-based diagnostic into a noninvasive blood or urine test.”

The study was published in the March 16, 2016, online edition of the journal Oncotarget.

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