Background: Peritoneal dissemination in colorectal cancer (CRC) is associated with poor prognosis due to limited efficacy of current therapeutic strategies. The cholinergic receptor nicotinic beta 2 subunit (CHRNB2), a component of the acetylcholine receptor, has been implicated in other malignancies, but its role in CRC remains unknown. Methods: This study evaluated the expression and function of CHRNB2 in CRC. CHRNB2 mRNA levels were quantified by qRT-PCR in cell lines and clinical specimens. Functional assays were conducted using CRC cell lines with high CHRNB2 expression, in which CHRNB2 was knocked down by shRNA. Cell proliferation, migration, and invasion were assessed in vitro. In vivo effects were evaluated using subcutaneous and peritoneal xenograft models. The impact of CHRNB2 monoclonal antibody (mAb) treatment on CRC cell proliferation was also examined. Clinical correlations were assessed between CHRNB2 expression and clinicopathological features, including recurrence patterns. Results: CHRNB2 expression varied among CRC cell lines, with the highest levels observed in LOVO cells. CHRNB2 knockdown significantly inhibited proliferation, migration, and invasion in vitro and suppressed tumor growth in vivo. CHRNB2 mAb treatment reduced cell proliferation. Clinically, high CHRNB2 expression correlated with a significantly higher cumulative rate of peritoneal recurrence, but not with recurrence in the liver, lungs, or lymph nodes. Multivariate analysis identified high CHRNB2 expression and T4 tumor depth as independent predictors of peritoneal recurrence. Conclusions: CHRNB2 promotes the malignant phenotype of CRC, particularly in peritoneal dissemination. These findings suggest that CHRNB2 may serve as a novel diagnostic biomarker and therapeutic target for CRC with peritoneal metastasis.
背景：结直肠癌（CRC）的腹膜播散因现有治疗策略效果有限而预后不良。胆碱能受体烟碱β2亚基（CHRNB2）作为乙酰胆碱受体的组成部分，在其他恶性肿瘤中已有研究，但其在CRC中的作用尚不明确。方法：本研究评估了CHRNB2在CRC中的表达及功能。通过qRT-PCR检测细胞系及临床样本中CHRNB2的mRNA水平。利用高表达CHRNB2的CRC细胞系进行功能实验，通过shRNA敲低CHRNB2表达，评估细胞增殖、迁移和侵袭能力。体内实验采用皮下及腹膜异种移植模型。同时检测CHRNB2单克隆抗体（mAb）对CRC细胞增殖的影响。分析CHRNB2表达与临床病理特征（包括复发模式）的相关性。结果：CHRNB2在CRC细胞系中表达各异，其中LOVO细胞表达水平最高。敲低CHRNB2能显著抑制体外细胞增殖、迁移和侵袭，并在体内抑制肿瘤生长。CHRNB2单克隆抗体处理可降低细胞增殖。临床分析显示，CHRNB2高表达与腹膜累积复发率显著升高相关，而与肝、肺或淋巴结复发无关。多变量分析确认CHRNB2高表达和T4肿瘤浸润深度是腹膜复发的独立预测因子。结论：CHRNB2促进CRC恶性表型，尤其在腹膜播散过程中发挥重要作用。这些发现提示CHRNB2可能作为腹膜转移性CRC的新型诊断生物标志物和治疗靶点。
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