Pancreatic cancer (PC) is a highly lethal malignancy: the majority of patients have locally advanced or metastatic disease at the time of diagnosis since signs and symptoms are mostly non specific and often evident only in late stages. Due to the crucial importance of an earlier identification of PC, there is substantial ongoing effort to identify serological biomarkers that would facilitate the timely detection of this malignant neoplasm. Protein Induced by Vitamin K Absence II (PIVKA-II) is an abnormal form of prothrombin released by the liver in absence of vitamin K(VK) or in presence of certain types of gastrointestinal malignancy. Many in vitro and in vivo studies have suggested anti-carcinogenic effects exerted by VK both directly and indirectly through post-translational activation of proteins such as PIVKA-II. In the last years it has been well established in literature that PIVKA-II plays an important role as a biomarker in hepatocellular carcinoma (HCC). Like the liver, the pancreas originate from the primitive foregut of the embryo, and it has been demonstrated that these organs have the capability to transdifferentiate into each other tissue. According to these recent findings, aim of this study is to analyze serum levels of PIVKA-II in PC patients, in order to determine its potential diagnostic relevance for this malignancy. For this purpose will be enrolled a total of 100 Caucasian subjects: 30 patients with PC, 30 patients with pancreatic benign disease and 40 healthy controls matched for age and sex. PIVKA- II serum concentrations will be tested by the electrochemiluminescence enzyme immunoassay method (CLEIA) on LUMIPULSE G1200 (Fujirebio-Europe, Belgium). PIVKA-II serum level will be related to the histopathological characterization of the pancreatic lesion. Moreover, patients will be screened for tumor markers currently used in PC (CA19.9, CA242, CEA). Statistical analyses will be performed by MedCalc V 4.30 Software (Italy).
Detection of pancreatic cancer at early stages remains a great challenge due to lack of specific detection tests despite many investigations have been conducted to find the appropriate serum biomarkers (Liu 2012, Chang 2017). Currently, several biomarkers such as carcinoembryonic antigen CEA, CA19.9, CA242 have been proposed for PC detection, although the clinical applicability of these tests remains unclear ( Herreros-Villanueva 2013). The recommendations in existing clinical practice guidelines on early diagnosis of PC are inconsistent: most of them endorse measuring serum CA19.9 as a complementary test, but also stated that it is not useful for diagnosing early pancreatic cancer or for screening (Takaori 2016). The discovery of a biomarker that would facilitate earlier identification of PC would greatly affect patient management and prognosis. Moreover, it has been reported that a combination of serum biomarkers increase specificity and sensitivity of individual test: in this aim the detection of a biomarker to complement others in diagnostic accuracy would be of really important to facilitate PC detection (Kamisawa 2016, Zhang 2015). In vitro and in vivo studies have suggested anti-carcinogenic effects exerted by VK both directly (given its ability to suppress cancer growth, induce apoptosis and differentiation in cancer cells) and indirectly through post-translational activation of proteins such as PIVKA-II (Dahlberg 2018) It is widely assumed that pancreas and liver retain a latent capability to transdifferentiate into each other¿s tissue because they originate from the primitive foregut of the embryo (Fei 2012, Gordillo 2015). Therefore, PIVKA-II expression, which is characteristic of HCC, can reasonably be present in PC, even if the mechanism of PIVKA-II pancreatic production is still unknown. According to these recent findings , this study is the first to investigate the performance of PIVKA-II as a novel biomarker for PC. Protein biomarkers ¿ such as PIVKA-II ¿ quantifiable in serum are the most suitable for clinical routine evaluation, since these tests require very small amounts of serum, are low-cost, have high reproducibility, and samples do not need any particular pretreatment (ie, extraction or purification) (Saitta 2017). In conclusion, including serum PIVKA-II measurement in the diagnostic work-up for PC could be considered a valuable additional tool in clinical practice.