Abstract
PURPOSE: This study seeks to resolve a fundamental question in oncology: Why do appendiceal and colorectal adenocarcinomas exhibit distinct liver metastasis rates? Building on our prior hypothesis published in the British Journal of Surgery, our institution has investigated potential DNA mutations within the carcinoembryonic antigen-related cell adhesion molecule (CEACAM5) gene's Pro-Glu-Leu-Pro-Lys (PELPK) motif to evaluate its role as a biomarker for liver metastasis risk. METHODS: Partnering with the Australian Genome Research Facility, the PELPK motif of CEACAM5 was analysed in colorectal and appendiceal adenocarcinomas to detect DNA mutations associated with liver metastasis. Additionally, our institution performed the COPPER trial to assess carcinoembryonic antigen (CEA) levels in portal versus peripheral blood in patients with appendiceal adenocarcinoma and a systematic review and meta-analysis of 136 studies on CEA's prognostic significance among patients with colorectal and appendiceal adenocarcinoma. RESULTS: No mutations were identified within the PELPK region. The COPPER trial further demonstrated no statistically significant differences in CEA levels between portal and peripheral blood in appendiceal adenocarcinoma. However, the systematic review and meta-analysis confirmed CEA's prognostic role in patients with appendiceal or colorectal adenocarcinoma. CONCLUSION: The absence of DNA mutations suggests that metastatic potential may be driven by downstream mRNA or protein modifications in the CEA PELPK region. Future work will include surface plasmon resonance studies to investigate CEA-receptor interactions and development of immunohistochemistry for CEA PELPK expression. Such findings are poised to redefine global strategies for cancer stratification and targeted immunotherapy, setting the stage for groundbreaking advancements in cancer prognosis and patient outcomes.