Background: Surgery still represents the gold standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant treatments (NAT), currently proposed for borderline and locally advanced PDACs, are gaining momentum even in resectable tumors due to the recent interesting concept of “biological resectability”. In this scenario, CA 19.9 is having increasing importance in preoperative staging and in the choice of therapeutic strategies. We aimed to assess the state of the art and to highlight the future perspectives of CA 19.9 use in the management of patients with resectable pancreatic cancer. Methods: A PubMed database search of articles published up to December 2021 has been carried out. Results: Elevated pre-operative levels of CA 19.9 have been associated with reduced overall survival, nodal involvement, and margin status positivity after surgery. These abilities of CA 19.9 increase when combined with radiological or different biological criteria. Unfortunately, due to strong limitations of previously published articles, CA 19.9 alone cannot be yet considered as a key player in resectable pancreatic cancer patient management. Conclusion: The potential of CA 19.9 must be fully explored in order to standardize its role in the “biological staging” of patients with resectable pancreatic cancer.

The development of new tools for the early detection of pancreatic ductal adenocarcinoma (PDAC) represents an area of intense research. Recently, the concept has emerged that multiplexed detection of different signatures from a single biospecimen (e.g., saliva, blood, etc.) may exhibit better diagnostic capability than single biomarkers. In this work, we develop a multiplexed strategy for detecting PDAC by combining characterization of the nanoparticle (NP)-protein corona, i.e., the protein layer that surrounds NPs upon exposure to biological fluids and circulating levels of plasma proteins belonging to the acute phase protein (APPs) family. As a first step, we developed a nanoparticle-enabled blood (NEB) test that employed 600 nm graphene oxide (GO) nanosheets and human plasma (HP) (5% vol/vol) to produce 75 personalized protein coronas (25 from healthy subjects and 50 from PDAC patients). Isolation and characterization of protein corona patterns by 1-dimensional (1D) SDS-PAGE identified significant differences in the abundance of low-molecular-weight corona proteins (20–30 kDa) between healthy subjects and PDAC patients. Coupling the outcomes of the NEB test with the circulating levels of alpha 2 globulins, we detected PDAC with a global capacity of 83.3%. Notably, a version of the multiplexed detection strategy run on sex-disaggregated data provided substantially better classification accuracy for men (93.1% vs. 77.8%). Nanoliquid chromatography tandem mass spectrometry (nano-LC MS/MS) experiments allowed to correlate PDAC with an altered enrichment of Apolipoprotein A-I, Apolipoprotein D, Complement factor D, Alpha-1-antichymotrypsin and Alpha-1-antitrypsin in the personalized protein corona. Moreover, other significant changes in the protein corona of PDAC patients were found. Overall, the developed multiplexed strategy is a valid tool for PDAC detection and paves the way for the identification of new potential PDAC biomarkers.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the “Big Five” lethal cancers, which include lung, bowel, breast and prostate cancer [...]

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