Short Communication
Trends of Molecular Research for Pancreatic Cancer Diagnostics: Insights of Clinician
Marius Petrulionis1*, Benediktas Kurlinkus2, Audrius Sileikis1 and Kestutis Strupas1
1Department of Surgery, Vilnius University, Lithuania
2Department of Hepatology, Gastroenterology and Dietology, Vilnius University, Lithuania
*Corresponding author: Marius Petrulionis, Department of Surgery, Vilnius University, Lithuania
Published: 17 Mar, 2017
Cite this article as: Petrulionis M, Kurlinkus B, Sileikis
A, Strupas K. Trends of Molecular
Research for Pancreatic Cancer
Diagnostics: Insights of Clinician. Clin
Oncol. 2017; 2: 1223.
Short Communication
Pancreatic cancer is an aggressive malignancy with very high negative impact for overall patients
survival and non-reducing incidence rates in western countries [1,2]. In comparison to other solid
tumors, pancreatic cancer has one of the highest rates of genetic alterations which lead to expression
of large amount of various proteins and metabolites. Due to recent improvement and innovations of
related technologies, research of pancreatic cancer proteome and metabolome is on the scope with
promising results for improvement in diagnostics and treatment of this cancer type. A lot of efforts
are being done worldwide searching for a sensitive, specific and cost-effective biomarkers which
could be used for more effective early diagnostics and management of pancreatic cancer [3,4].
Galectins can regulate a wide variety of biological processes because of their ability to bind highly
modifiable carbohydrate ligands. An over-expression of galectin-1 was discovered in Pancreatic
Intraepithelial Neoplasia (PanIN), but not in healthy pancreas [5]. Since this form of neoplasia
is recognized as the immediate precursor lesion of pancreatic cancer, galectin-1 could serve as a
biomarker for improving early diagnostics. Upregulation of DJ-1, another multifunctional protein,
previously has been identified in blood serum and pancreatic juicein individuals with pancreatic
cancer compared to controls [6,7].
The S100 family is rich of clinically significant proteins. The expression of S100A6 was reported
to be increased in pancreatic juice during pancreatic cancer progression. While this increase of
expression appears at the early cancer stage it enables the possibility of early diagnostics. S100A6
proved to be highly sensitive biomarker when measured in endoscopic ultrasonography guided fine
needle aspiration specimens reaching up to 97.06% diagnostic sensitivity. S100P, another member
of this family, was suggested to be sensitive and specific biomarker with a potential to be identified
in pancreatic intraepithelial neoplasia. It was recommended to be assessed in duodenal juice during
routine upper endoscopy with the intention to become a screening tool for the pancreatic carcinoma
[8].
Apolipoproteins form a lipoprotein family with a function to regulate metabolism of plasma
lipoproteins. Changes in their expression were reported to correlate with pancreatic cancer.Findings
ofPadoan et al. indicate that the expression of apolipoprotein A-I is reduced in patients with
pancreatic carcinoma [9]. Likewise, reduction of this protein level was shown to be associated with
an increased risk of colorectal cancer [10]. Research of recent years has shown that metabolomics
could be used for more precise pancreatic cancer diagnostics [4]. Sugimoto et al. [11] identified forty
eight metabolites as biomarker candidates in easily accessible sample sourceslike saliva. Investigation
of urine metabolome was shown to be useful non-invasive technique for the pancreatic cancer
detection [12]. Furthermore, this approach permits separation of patients with intermediate and
advanced pathologic staging. Blood serum samples from patients with pancreatic carcinoma and
healthy controls were analyzed and scientists identified that concentrations of taurine, choline and
glucose plus triglycerides were significantly higher in the carcinoma group [13]. Another similar
study concluded that metabolites have a higher accuracy than conventionally used tumor markers
CA19-9 and CEA for differential diagnostics of pancreatic cancer [14].
In patients with pancreatic cancer, plasma amino acid concentrations are influenced by
metabolism of cancerous tissues, systemic effects of cancer for body metabolism and dysfunctions
of other organs including liver and kidney. Therefore, measurements of plasma amino acids during
various stages of pancreatic cancer could be a valuable source of information for early diagnostics.
Group of scientists performed amino acid profiling and multi-marker models of serum samples in pancreatic carcinoma patients, pancreatitis patients and healthy
controls [15]. The results showed that combined amino acid-based
metabolite panel is superior to CA19-9 alone in differentiating
between these groups. Study with a large number of fasting plasma
samples from pancreatic cancer patients, chronic pancreatitis
patients and healthy controls was conducted at multi-institutions
in Japan [16]. Concentrations of amino acids were measured and
significant increases in Ser concentrations and significant decreases
in the concentrations of 14 amino acids (Thr, Asn, Pro, Ala, Cit, Val,
Met, Leu, Tyr, Phe, His, Trp, Lys and Arg) were observed in cancer
patients compared with healthy subjects. In a prospective study,
elevated branched-chain amino acid concentrations in prediagnostic
plasma samples were associated with more than twofold increased
pancreatic cancer risk, with the strongest prediction value observed
in samples collected 2–5 years prior to pancreatic cancer diagnosis,
isoleucine, leucine and valine being the most significant [17].
Results of overall survival are increasing in specialized pancreas
surgery centres with relatively low postoperative complication rates
after surgery [18]. Due to issues, radiologic assessment can hardly
be applied as first step method for screening of pancreatic cancer in
certain risk groups. Therefore, novel biological markers validated
in easily accessible body fluids, complementing or substituting
conventional CA19-9 and CEA, are considered as a necessity for
further success improving treatment results of pancreatic cancer
patients.
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