Molecular analysis highlights TREM2 as a discriminating biomarker for patients suffering from pancreatic ductal adenocarcinoma

Abstract

Pancreatic cancer is projected to become the second leading cause of cancer-related deaths by 2030, with its mortality continuing to rise, unlike other common cancers such as breast or colorectal. Late-stage diagnosis, often accompanied by metastatic dissemination, drastically impairs patient survival and underscores the urgent need for improved biomarkers to guide therapeutic strategies. While molecular signatures have been proposed to stratify pancreatic cancer patients, their ability to predict outcomes remains limited. In this study, we applied established molecular signatures to our in-house transcriptomic data from a cohort of pancreatic cancer patients. We took advantage of published datasets to construct comprehensive atlases of cells present in primary and metastatic pancreatic cancers. The atlas of metastasis samples, representative of routinely harvested patient biopsies, revealed that monocyte/macrophage signatures provided superior discriminatory power compared to existing molecular classifications. Notably, the abundance of TREM2-expressing macrophages emerged as a significant parameter for stratifying patients. Our findings position TREM2⁺ macrophages as a promising biomarker for pancreatic cancer, with potential to enhance patient stratification and inform the development of targeted therapies. This work highlights the critical role of tumor-associated macrophages in pancreatic cancer progression and lays the groundwork for further functional and translational studies.

Keywords: Macrophages; Metastasis; Molecular analysis; Pancreatic ductal adenocarcinoma (PDAC); Primary tumor; Tumor microenvironment.