MFAP2 promotes the progress of esophageal squamous cell carcinoma by enhancing PTGS2 signaling.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies, accounting for over 85% of all esophageal cancers worldwide and over 90% in China. Due to the absence of effective early diagnostic tools and therapeutic approaches, the 5-year survival rate remains below 30%. Thus, it is crucial to further investigate the molecular mechanisms underlying ESCC. By analyzing differentially expressed genes in esophageal adenocarcinoma (EAC) and ESCC, we identified 127 genes that were significantly upregulated in ESCC and enriched in extracellular matrix organization. Notably, MFAP2 (microfibril associated protein 2), a matrix-related molecule with unclear function, was found to be highly expressed in ESCC in both the TCGA database and our RNA sequencing data. Its elevated levels were associated with cancer progression. Western blot, immunofluorescence, and immunohistochemistry revealed that MFAP2 protein was highly expressed in ESCC and predominantly distributed in the extracellular matrix, cytoplasm, and partially in the nucleus. In vitro functional experiments demonstrated that overexpressing MFAP2 had no significant effect on cell proliferation but inhibited cell migration and invasion. In vivo xenograft assays showed that MFAP2 enhanced the growth of the KYSE-450 cancer cell line, though no statistical difference was observed in KYSE-140. Bioinformatics analysis revealed a positive correlation between MFAP2 expression and anti-tumor (M1 type) macrophages in EAC tissues, whereas in ESCC tissues, MFAP2 correlated positively with non-activated (M0 type) macrophages. RNA sequencing indicated that MFAP2 is involved in immune pathways and can promote PTGS2 expression. Collectively, this study preliminarily evaluates the function and potential molecular mechanism of MFAP2 in ESCC, offering new therapeutic targets and ideas for ESCC treatment.