Identification of the M2 Macrophage-associated Gene THBS2 as a Predictive Marker for Inflammatory Cancer Transformation

Abstract

Ulcerative colitis (UC)-induced colitis-associated colorectal cancer (CAC) has a worse prognosis than sporadic colorectal cancer. And with the incidence of ulcerative colitis on the rise, it is critical to identify new therapeutic targets in time to stop the progression of inflammation to cancer. Through immunohistochemistry (IHC) and Gene Expression Omnibus (GEO) database analysis, we acquired the gene M2DEG, which is differentially expressed in M2 macrophages. The impact of M2DEG on the immune environment and clinical variables was confirmed through various data sets and actual tissue samples. Our findings indicate that patients with UC exhibiting reduced M2 macrophage infiltration tend to have more widespread disease, elevated endoscopic Mayo scores, and a higher probability of developing CAC. Through examining the string of M2DEG between UC and CAC, THBS2 emerged as a key marker. Elevated levels of THBS2 were notably linked to reduced overall survival (OS) and progression-free survival (RFS), and this heightened THBS2 expression played a crucial role in the spread of tumors, as verified by immunohistochemical studies. To sum up, patients with UC exhibiting reduced M2 macrophage infiltration have a higher propensity for CAC development, making THBS2 a crucial focus for converting UC into CAC. Furthermore, identifying antibody analogues targeting THBS2 could potentially lower the likelihood of CAC transformation in patients with UC.