Circulating EMID2 as a Prognostic Biomarker of Poor Outcomes in Patients with Metastatic Colorectal Cancer.

Abstract

Background: EMID1 and EMID2 (also known as type XXVI collagen) are extracellular matrix (ECM) proteins that belong to the EDEN gene superfamily. Both proteins feature EMI domains, implicating them in protein-protein interactions and ECM remodeling. Despite structural similarities EMID1 and EMID2 have distinct functions with EMID1 primarily expressed in epithelial cells and EMID2 in mesenchymal cells. Previous studies have shown that while EMID1 could promote metastasis EMID2 might inhibit tumor growth and dissemination.

Objectives: Little is known about the specific functions and mechanisms of EMID1 and EMID2 in tumor development. Therefore, this study aims to explore the biomarker potential of EMID 1 and EMID2 in cancer.

Design: Retrospective study including a cross-sectional and a prognostic cohort to evaluate the biomarker potential of EMID1 and EMID2 in cancer.

Methods: We developed 2 competitive ELISAs targeting the N-terminal of EMID1 and EMID2. We compared EMID1 and EMID2 levels in serum from patients with different types of cancer (n = 216) to levels in healthy controls (n = 33). Thereafter, we measured EMID1 and EMID2 levels in a second cohort of patients with metastatic colorectal cancer (mCRC; n = 212) in stage IV treated with chemotherapy in combination with bevacizumab.

Results: The developed EMID1 and EMID2 ELISAs were specific, sensitive and robust. We did not find significant differences in EMID1 and EMID2 levels between patients with cancer and healthy controls, indicating limited diagnostic utility in cancer. However, in patients with mCRC, high EMID2 levels were associated with shorter PFS (241 days) compared to low levels (298 days) independently of other risk factors (HR = 1.57, 95% CI 1.04-2.36, P = .031). Kaplan-Meier survival analysis showed no association between low or high levels of EMID1 or EMID2 and overall survival (OS).

Conclusion: This study highlights EMID2 as prognostic biomarker in patients with mCRC, where higher levels correlated with more aggressive disease and shorter PFS. Future research should focus on elucidating the mechanisms underlying EMID2 degradation and its implications in cancer progression. Although EMID1 did not show diagnostic or prognostic value in this study, its biomarker potential in other types of cancer or benign diseases warrants further investigation.