Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigated the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. We extracted differentially expressed genes from the GSE140973, the overlapping genes combined with 151 Wnt/β-Catenin signaling pathway-related genes were identified. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene, through cell experimental, scrutinized the impact of cetuximab and PLCB3 on CRC cellular progression. The study identified 26 overlapping genes. High expression of PLCB3, correlated with poorer prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both β-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings revealed PLCB3 promoted cetuximab inhibition on Wnt/β-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. The study emphasized the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppressed Wnt/β-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offered fresh perspectives on cetuximab mechanism in CRC.

结直肠癌 (CRC) 通常需要西妥昔单抗（一种 EGFR 靶向单克隆抗体）进行治疗。尽管具有临床实用性，西妥昔单抗的具体作用机制仍然难以捉摸。本研究调查了 PLCB3（一种潜在的 CRC 致癌基因）对西妥昔单抗治疗的影响。我们从GSE140973中提取差异表达基因，并鉴定出重叠基因与151个Wnt/β-Catenin信号通路相关基因。然后，我们进行了生物信息学分析以查明枢纽基因。随后，我们研究了该hub基因的临床表达特征，通过细胞实验，考察了西妥昔单抗和PLCB3对CRC细胞进展的影响。该研究确定了 26 个重叠基因。 PLCB3的高表达与较差的预后相关。 PLCB3 成为与患者预后相关的重要癌基因。体外测试表明，西妥昔单抗对 CRC 细胞具有细胞毒作用，PLCB3 敲低可抑制 CRC 细胞进展。此外，西妥昔单抗治疗导致 β-连环蛋白和 PLCB3 表达减少，同时增加 E-钙粘蛋白表达。这些发现表明 PLCB3 促进西妥昔单抗对 Wnt/β-连环蛋白信号传导的抑制。最后，西妥昔单抗与 Wnt 激活剂 (IM12) 和 PLCB3 的同时应用证明可抑制 CRC 增殖、迁移和侵袭。该研究强调了 PLCB3 在 CRC 中的关键作用及其增强西妥昔单抗治疗疗效的潜力。此外，西妥昔单抗通过抑制 Wnt/β-catenin 通路来调节 PLCB3 的表达，从而抑制结直肠癌的进展。这项研究为西妥昔单抗治疗结直肠癌的机制提供了新的视角。