Salivary Polyamines Help Detect High-Risk Patients with Pancreatic Cancer: A Prospective Validation Study

Abstract

Pancreatic cancer is one of the most malignant cancer types and has a poor prognosis. It is often diagnosed at an advanced stage because of the absence of typical symptoms. Therefore, it is necessary to establish a screening method for the early detection of pancreatic cancer in high-risk individuals. This is a prospective validation study conducted in a cohort of 1033 Japanese individuals (male, n = 467, age = 63.3 ± 11.5 years; female, n = 566, age = 64.2 ± 10.6 years) to evaluate the use of salivary polyamines for screening pancreatic diseases and cancers. Patients with pancreatic cancer were not included; however, other pancreatic diseases were treated as positive cases for accuracy verification. Of the 135 individuals with elevated salivary polyamine markers, 66 had pancreatic diseases, such as chronic pancreatitis and pancreatic cysts, and 1 had gallbladder cancer. These results suggest that the salivary polyamine panel is a useful noninvasive pancreatic disease screening tool.

The Potential of Salivary Biomarkers in Early Detection of Pancreatic Ductal Adenocarcinoma: A Systematic Review

“…We evaluated studies assessing various PDAC saliva biomarkers, including metabolites, proteomic markers, circulating tumor DNA/RNA, microbes, and EVs. Notably, polyamines like spermine and N1-acetylspermidine showed significantly elevated levels in PDAC patient saliva, indicative of cellular polyamine dyshomeostasis associated with PDAC oncogenesis [ 8 , 14 ]. Circulating tumor RNA species, such as miR-3679-5p and the long non-coding RNA PVT1, were differentially expressed in PDAC saliva compared to controls, highlighting their regulatory function and diagnostic value [ 10 , 15 ].…”

“…Alterations in metabolite levels act as red flags for malignant transformation-induced metabolic shifts. Certain metabolites, like polyamines, show elevated salivary levels due to dysregulation of key oncogenic pathways in PDAC [ 8 , 9 ]. Signature protein changes also arise from PDAC onset and progression.…”

Critical Factors in Sample Collection and Preparation for Clinical Metabolomics of Underexplored Biological Specimens

“…Additionally, some protocols require patient rest and the absence of oral-facial movements in the 5 min preceding the collection [ 162 ]. In terms of hygiene, most studies do not allow the application of oral hygiene products, in which the typical recommendation is washing the oral cavity with water [ 163 , 164 , 165 , 166 , 167 ]. Another important point is the type of saliva that will be used: stimulated or unstimulated.…”

Pancreatic Cancer and Detection Methods

“…Nevertheless, the drawback of using CA19-9 lies in its lack of specificity, as false positive results in the presence of other bodily cancerous parts such as the colon, gastric, and biliary tract, and it fails to differentiate between PC and chronic pancreatitis [ 99 , 112 , 113 ]. Therefore, using CA19-9 alone for screening is insufficient, and a combination of CA19-9 with other biomarkers can enhance the screening and diagnostic efficacy by increasing sensitivity and specificity [ 111 , 114 , 115 , 116 , 117 ]. To this end, several reports have suggested combining CA19-9 with other biomarkers, such as Carcinoembryonic antigen (CEA).…”

“…In addition, other urinary biomarkers, including polyamines, have shown high sensitivity in distinguishing PC from chronic pancreatitis. Salivary biomarkers have also been studied, with N 1 , and N 12 -diacetylspermine from saliva collected from patients with PC showing high AUC values [ 114 ]. However, the protein markers in saliva have a limitation in that false positives can occur in patients with other types of cancer.…”