Salivary MicroRNA in Pancreatic Cancer Patients

1. PLoS One. 2015 Jun 29;10(6):e0130996. doi: 10.1371/journal.pone.0130996.
eCollection 2015.

Salivary MicroRNA in Pancreatic Cancer Patients.

Humeau M(1), Vignolle-Vidoni A(2), Sicard F(3), Martins F(4), Bournet B(2),
Buscail L(2), Torrisani J(3), Cordelier P(3).

Author information:
(1)Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul
Sabatier, UMR1037 CRCT, F-31000 Toulouse, France; Department of Surgery, CHU
Toulouse- Rangueil, Toulouse, France.
(2)Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul
Sabatier, UMR1037 CRCT, F-31000 Toulouse, France; Department of
Gastroenterology, CHU Toulouse- Rangueil, Toulouse, France.
(3)Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul
Sabatier, UMR1037 CRCT, F-31000 Toulouse, France.
(4)Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse,
France; INSERM U1048, F-31000 Toulouse, France.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer death in
Western countries, with the lowest 1-year survival rate among commonly diagnosed
cancers. Reliable biomarkers for pancreatic cancer diagnosis are lacking and are
urgently needed to allow for curative surgery. As microRNA (miRNA) recently
emerged as candidate biomarkers for this disease, we explored in the present
pilot study the differences in salivary microRNA profiles between patients with
pancreatic tumors that are not eligible for surgery, precancerous lesions,
inflammatory disease or cancer-free patients as a potential early diagnostic
tool.
METHODS: Whole saliva samples from patients with pancreatic cancer (n = 7),
pancreatitis (n = 4), IPMN (n = 2), or healthy controls (n = 4) were obtained
during endoscopic examination. After total RNA isolation, expression of 94
candidate miRNAs was screened by q(RT)PCR using Biomark Fluidgm. Human-derived
pancreatic cancer cells were xenografted in athymic mice as an experimental
model of pancreatic cancer.
RESULTS: We identified hsa-miR-21, hsa-miR-23a, hsa-miR-23b and miR-29c as being
significantly upregulated in saliva of pancreatic cancer patients compared to
control, showing sensitivities of 71.4%, 85.7%, 85,7% and 57%, respectively and
excellent specificity (100%). Interestingly, hsa-miR-23a and hsa-miR23b are
overexpressed in the saliva of patients with pancreatic cancer precursor
lesions. We found that hsa-miR-210 and let-7c are overexpressed in the saliva of
patients with pancreatitis as compared to the control group, with sensitivity of
100% and 75%, and specificity of 100% and 80%, respectively. Last hsa-miR-216
was upregulated in cancer patients as compared to patients diagnosed with
pancreatitis, with sensitivity of 50% and specificity of 100%. In experimental
models of PDAC, salivary microRNA detection precedes systemic detection of
cancer cells markers.
CONCLUSIONS: Our novel findings indicate that salivary miRNA are discriminatory
in pancreatic cancer patients that are not eligible for surgery. In addition, we
demonstrate in experimental models that salivary miRNA detection precedes
systemic detection of cancer cells markers. This study stems for the use of
salivary miRNA as biomarker for the early diagnosis of patients with
unresectable pancreatic cancer.

DOI: 10.1371/journal.pone.0130996
PMCID: PMC4486170
PMID: 26121640 [Indexed for MEDLINE]

Conflict of interest statement: Competing Interests: The authors have filed a
patent on the “use of salivary microRNA for the diagnosis of pancreatic cancer”.
A draft has been written in collaboration with our IP department (INSERM
Transfert), and deposited under the # EP15305020.8 but is not yet available
online. Nonetheless, this does not alter the authors’ adherence to all PLOS ONE
policies on sharing data and materials. The authors don’t have other relevant
declarations relating to employment, consultancy, patents, products in
development or modified products.

Auteurs Bordeaux Neurocampus