Expression Pattern of AIFM3, VGLL4, and WNT4 in Patients with Different Stages of Colorectal Cancer.

Background/objectives: Colorectal cancer (CRC) remains a significant health burden, and its delayed diagnosis at advanced stages leads to poor survival outcome. Detection of known and novel prognostic markers is essential. In this study, the status of likely prognostic markers-the apoptotic inducing factor (AIFM3), vestigial-like family member 4 (VGLL4), and WNT4-was evaluated.

Methods: AIFM3, VGLL4, and WNT4 expression in CRC tissues across different stages (Dukes A-D) were analyzed using histological immunofluorescence staining and RNA sequencing analyses.

Results: In advanced CRC stages, progressive loss of normal crypt architecture, reduction of goblet cells, and necrotic debris were detected along with differential expression patterns of AIFM3, VGLL4, and WNT4. AIFM3 exhibited high reactivity in the lamina propria of healthy tissue and Dukes A, but this was diminished in advanced CRC stages. VGLL4 expression, initially confined to the lamina propria, increased significantly in the epithelium of Dukes B and C, with a cytoplasmic localization pattern. WNT4 expression was elevated in the CRC epithelium across all stages, contrasting with a significant reduction in lamina propria reactivity. RNA sequencing corroborated these findings, showing significant downregulation of AIFM3 and WNT4 and upregulation of VGLL4 in CRC tissues compared to controls. Expression of AIFM3 and WNT4 showed no correlation with survival outcome, while low VGLL4 expression was correlated with better survival outcome.

Conclusions: The results suggest distinct roles for AIFM3, VGLL4, and WNT4 in CRC progression, highlighting only VGLL4 as a potential prognostic marker. Further evaluation of VGLL4 and its specific role in CRC progression remains to be elucidated.