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.
背景/目的：结直肠癌（CRC）仍是重大的健康负担，其晚期诊断延迟导致生存预后不良。检测已知及新型预后标志物至关重要。本研究评估了潜在预后标志物——凋亡诱导因子（AIFM3）、退化样家族成员4（VGLL4）及WNT4的表达状态。方法：采用组织免疫荧光染色与RNA测序分析技术，检测不同分期（Dukes A–D）结直肠癌组织中AIFM3、VGLL4和WNT4的表达水平。结果：在晚期结直肠癌阶段，观察到正常隐窝结构的进行性破坏、杯状细胞减少及坏死碎片出现，同时AIFM3、VGLL4和WNT4呈现差异化表达模式。AIFM3在健康组织及Dukes A期组织的固有层中呈高反应性，但在晚期结直肠癌阶段显著减弱。VGLL4表达最初局限于固有层，在Dukes B期和C期上皮组织中显著增强，并呈现胞质定位特征。WNT4在所有分期的结直肠癌上皮组织中表达升高，而固有层反应性显著降低。RNA测序结果验证了上述发现：与对照组相比，结直肠癌组织中AIFM3和WNT4显著下调，VGLL4显著上调。AIFM3和WNT4表达与生存预后无相关性，而低VGLL4表达与更好的生存预后相关。结论：研究提示AIFM3、VGLL4和WNT4在结直肠癌进展中发挥不同作用，其中仅VGLL4具备成为潜在预后标志物的价值。VGLL4在结直肠癌进展中的具体作用机制仍有待进一步阐明。
Expression Pattern of AIFM3, VGLL4, and WNT4 in Patients with Different Stages of Colorectal Cancer
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