Salivary Transcriptomic Biomarkers for Detection of Resectable Pancreatic Cancer

Zhang, Lei; Farrell, James J.; Zhou, Hui; Elashoff, David; Akin, David; Park, No–Hee; Chia, David; Wong, David T.

doi:10.1053/j.gastro.2009.11.010

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Volume 138, Issue 3 , Pages 949-957.e7, March 2010

Salivary Transcriptomic Biomarkers for Detection of Resectable Pancreatic Cancer

Lei Zhang
- School of Dentistry and Dental Research Institute, University of California-Los Angeles, Los Angeles, California
James J. Farrell
- Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California
Hui Zhou
- School of Dentistry and Dental Research Institute, University of California-Los Angeles, Los Angeles, California
David Elashoff
- Department of Biostatistics, School of Public Health, University of California-Los Angeles, Los Angeles, California
David Akin
- School of Dentistry and Dental Research Institute, University of California-Los Angeles, Los Angeles, California
No–Hee Park
- School of Dentistry and Dental Research Institute, University of California-Los Angeles, Los Angeles, California
- Division of Hematology & Oncology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California
- Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, California
David Chia
- Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, California
David T. Wong
- School of Dentistry and Dental Research Institute, University of California-Los Angeles, Los Angeles, California
- Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, California
- Division of Head and Neck Surgery/Otolaryngology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California
- Henry Samueli School of Engineering and Applied Science, University of California-Los Angeles, Los Angeles, California
- Reprint requests Address requests for reprints to: David T. Wong, DMD, DMSc, Felix and Mildred Yip endowed professor, Division of Oral Biology and Medicine; associate dean for research, School of Dentistry; director, Dental Research Institute, University of California at Los Angeles, 10833 Le Conte Ave, 73-017 CHS, Los Angeles, California 90095. fax: (310) 825-7609

Received 10 August 2009; accepted 9 November 2009. published online 19 November 2009.

Background & Aims

Lack of detection technology for early pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. New strategies and biomarkers for early detection are sorely needed. In this study, we have conducted a prospective sample collection and retrospective blinded validation to evaluate the performance and translational utilities of salivary transcriptomic biomarkers for the noninvasive detection of resectable pancreatic cancer.

Methods

The Affymetrix HG U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) was used to profile transcriptomes and discover altered gene expression in saliva supernatant. Biomarkers discovered from the microarray study were subjected to clinical validation using an independent sample set of 30 pancreatic cancer patients, 30 chronic pancreatitis patients, and 30 healthy controls.

Results

Twelve messenger RNA biomarkers were discovered and validated. The logistic regression model with the combination of 4 messenger RNA biomarkers (KRAS, MBD3L2, ACRV1, and DPM1) could differentiate pancreatic cancer patients from noncancer subjects (chronic pancreatitis and healthy control), yielding a receiver operating characteristic plot, area under the curve value of 0.971 with 90.0% sensitivity and 95.0% specificity.

Conclusions

The salivary biomarkers possess discriminatory power for the detection of resectable pancreatic cancer, with high specificity and sensitivity. This report provides the proof of concept of salivary biomarkers for the noninvasive detection of a systemic cancer and paves the way for prediction model validation study followed by pivotal clinical validation.

Keywords: Salivary Biomarker, Resectable Pancreatic Cancer, Salivary Transcriptome

Abbreviations used in this paper: AUC, area under the curve, MIAME, minimum information about a microarray experiment, ROC, receiver operating characteristic