Prognostic biomarkers related to tumoral microenvironment in pancreatic ductal adenocarcinoma: a systematic review

Over the past decades, pancreatic ductal adenocarcinoma (PDAC) has been coming into view due to increased mortality, the 5-year survival rate being the lowest of all cancers (around 6%). In PDAC, microenvironmental components possess prognostic relevance. The aim of this article is to perform a review of studies evaluating the composition of the tumor microenvironment to identify tumor microenvironment-related prognostic biomarkers in patients with PDAC. A literature search has been performed in three major databases PubMed (R), Embase (R), Web of Science (R) using the search terms: pancreatic adenocarcinoma in combination with one of the following: alpha-smooth muscle actin (alpha-SMA), collagen I, cluster of differentiation (CD)31, CD105, CD3-CD4-CD8, CD68 and CD206. Total number of articles identified through database searching was 1185. After title and abstract review, we have selected 92 articles in which the markers sought were studied. Tumor microenvironment-related biomarkers appear to also possess role in monitoring the response to treatment. Thus, CD105 angiogenetic immunomarker, stromal immunomarkers such as alpha-SMA and collagen I, immune cells markers represented by CD4/CD8 ratio, CD206 and CD68 were correlated with negative prognosis, while CD3+, CD8+ immune cells markers and CD31 angiogenetic immunomarker proved to be correlated with good prognosis. Furthermore, most studies were performed on resected specimens and culture cells, while only a few studies used specimens obtained through endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). To increase the therapeutic response and reduce toxicity, prognostic targets should be determined on a large scale, not only based on resected specimens. EUS-FNB represents a feasible method to provide sufficient tissue for diagnosis and additional immunohistochemistry analysis.