The Prognostic and Predictive Value of METTL3 in Metastatic Colorectal Cancer

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and its incidence continues to rise. The prognosis remains poor, especially for patients with metastatic disease. Methyltransferase-like 3 (METTL3) is the primary catalytic enzyme in the N6-methyladenosine (m6A) methyltransferase system. METTL3 plays a dual role, acting as either an oncogene or a tumor suppressor depending on the cancer type. It also plays a significant role in the response to treatment. However, its specific function in CRC remains unclear.

A prospective cohort of sixty patients with metastatic colorectal cancer (mCRC) was enrolled at the South Egypt Cancer Institute (SECI). METTL3 expression was evaluated using immunohistochemistry (IHC). This study aimed to investigate METTL3 expression in CRC and its association with clinicopathological features and clinical outcomes in patients treated with oxaliplatin (OX)- and 5-fluorouracil (5-FU)-containing regimens.

Our findings revealed that elevated METTL3 expression correlated with increased synchronous metastasis and a greater number of metastatic sites. In addition, elevated METTL3 was associated with increased lymphovascular invasion, perineural invasion, a non-brisk immune response, and greater tumor depth. Notably, right-sided tumors exhibited significantly higher METTL3 expression compared to those on the left side and in the rectum. Finally, METTL3 overexpression was associated with a lower response rate to OXA-based therapy, as well as shorter progression-free survival (PFS) and overall survival (OS), all with p < 0.05.

METTL3 may serve as both a prognostic and predictive biomarker in colorectal cancer (CRC).