结直肠癌中GNB2、PKM2和β-catenin的表达及其与肿瘤出芽的关系OA

Objective:Tumor budding is a distinct cellular phenomenon in colorectal cancer(CRC)and has important prognostic significance.This study aims to investigate the expression of G protein subunit beta 2(GNB2),pyruvate kinase M2(PKM2),and β-catenin in CRC and explore their associations with clinicopathological characteristics and tumor budding. Methods:Clinicopathological data of 178 patients with CRC who were treated at Affiliated Fuding Hospital,Fujian University of Traditional Chinese Medicine from January 2023 to December 2024 were retrospectively collected.Immunohistochemical staining was performed to detect the expression of GNB2,PKM2,and β-catenin in CRC tissues and adjacent normal tissues,and their associations with clinicopathological characteristics were analyzed.Furthermore,differences in the expression of GNB2,PKM2,and β-catenin between the primary tumor areas and tumor budding areas were evaluated in 68 CRC cases with intermediate-and high-grade tumor budding. Results:The high expression rates of GNB2 and PKM2 in CRC tissues were 83.7%and 87.6%,respectively,while the ectopic expression rate of β-catenin was 96.6%.High expression of GNB2 and PKM2 was significantly associated with histological grade,depth of invasion,lymph node metastasis,perineural invasion,vascular tumor thrombus,clinical stage,and tumor budding(all P<0.05).Aberrant β-catenin expression was significantly associated with histological grade,depth of invasion,and clinical stage(all P<0.05).Spearman correlation analysis showed that GNB2 expression was positively correlated with PKM2 expression(r=0.435,P<0.01).Aberrant β-catenin expression was positively correlated with GNB2 and PKM2 expression(r=0.255 and r=0.246,respectively;both P<0.01).Among the 68 CRC cases with intermediate-to high-grade tumor budding,the high expression rate of GNB2 in tumor budding areas was 98.5%,showing no significant difference compared with that in primary tumor areas(97.1%,P>0.05).The high expression rate of PKM2 in tumor budding areas was 38.2%,which was significantly lower than that in primary tumor areas(97.1%,P<0.01).Nuclear localization of β-catenin in tumor budding areas was observed in 80.9%of cases,significantly higher than that in primary tumor areas(7.4%,P<0.01). Conclusion:Tumor budding fronts in CRC exhibit high GNB2 expression,reduced PKM2 expression,and nuclear translocation of β-catenin.These findings suggest that GNB2,PKM2,and β-catenin may cooperatively participate in tumor budding and CRC progression through the Wnt/β-catenin signaling pathway.This study provides potential insights and a theoretical basis for identifying novel therapeutic targets and developing anti-tumor budding strategies in CRC.