# Cholinergic Receptor Nicotinic Beta 2 Subunit Promotes the Peritoneal Disseminating Metastasis of Colorectal Cancer

## TL;DR

This study shows that the CHRNB2 protein promotes peritoneal metastasis in colorectal cancer and could be a new target for treatment.

## Contribution

The study identifies CHRNB2 as a novel therapeutic target for peritoneal metastasis in colorectal cancer.

## Key findings

- CHRNB2 knockdown reduced cancer cell proliferation, migration, and peritoneal metastasis in experiments.
- High CHRNB2 expression in patients correlates with increased peritoneal recurrence risk.
- Anti-CHRNB2 monoclonal antibodies inhibited cancer cell growth, suggesting therapeutic potential.

## Abstract

Colorectal cancer with peritoneal metastasis is associated with a particularly poor prognosis, underscoring the urgent need for novel therapeutic strategies. In this study, CHRNB2 was investigated as a potential molecular target. Knockdown of CHRNB2 in colorectal cancer cell lines significantly suppressed cell proliferation, migration, and invasion and notably reduced the ability to form peritoneal metastases. Furthermore, treatment with anti-CHRNB2 monoclonal antibodies inhibited cell proliferation, suggesting potential therapeutic utility. Clinical analysis of colorectal cancer specimens revealed a significant correlation between high CHRNB2 expression and increased risk of peritoneal recurrence, indicating its involvement in metastatic progression. These findings suggest that CHRNB2 plays a critical role in the malignant phenotype associated with peritoneal dissemination and may serve as a promising target for therapeutic intervention in colorectal cancer patients with or at risk for peritoneal metastasis.

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.