Correlation between the expression of metastatic tumor antigen 1 splice variants and aggressive features of colorectal cancer

Colorectal cancer (CRC) is among the most prevalent malignancies in the gastrointestinal tract, and distant metastasis remains the primary cause of poor prognosis in CRC patients. Therefore, elucidating the molecular mechanisms underlying CRC invasion and migration has become extremely important. The overexpression of the MTA1 protein is consistently associated with cell proliferation, invasion, and migration in various tumor types; however, the key molecular mechanism through which MTA1 exerts its downstream effects involving alternative splicing at the posttranscriptional level during the progression of CRC remains unknown. In this study, clinical specimens from 32 CRC patients were analyzed using PCR, Western blotting, and immunohistochemistry (IHC) combined with bioinformatics. The results demonstrated that MTA1 expression was significantly upregulated in CRC tissues. Further PCR analysis revealed a significant upregulation of the MTA1dE18 splice variant in tumor tissues (P < 0.01), whereas no significant difference in MTA1dE4 expression was observed. Moreover, high expression of MTA1dE18 was significantly associated with advanced lymph node involvement (N stage: χ² = 7.242; P = 0.007) and distant metastasis (M stage: χ² = 21.89; P < 0.001). Kaplan–Meier curves revealed that patients with higher MTA1dE18 expression had poorer long-term prognosis, with a median survival of 28.0 months (P = 0.001). Subgroup analysis revealed that among CRC patients with lymph node metastasis, those with lower MTA1dE18 expression had significantly longer overall survival (37.5 vs. 21.0 months, P = 0.006). However, no significant difference was observed in N0 patients. Among patients with locally advanced disease, the high-MTA1dE18-expression group (n = 11) had a shorter median overall survival (21.0 months) than the low-expression group did (P = 0.006). Furthermore, analyses of data from the UALCAN database and Metascape online tool suggested that MTA1 may facilitate tumor cell invasion and migration by activating the TGF-β/SMAD signaling pathway. In conclusion, MTA1dE18 is markedly overexpressed in CRC tissues and strongly associated with adverse prognosis, suggesting its potential as a sensitive biomarker for predicting patient outcomes.