Abstract
BackgroundAmine oxidase copper containing 1 (AOC1) is a gene whose biological function in colorectal cancer (CRC) has not been elucidated. Therefore, the purpose of this study was to investigate the clinical significance of AOC1 expression in CRC and its biological function in CRC cell lines.Materials and Methods AOC1 expression levels were examined in paired CRC and peritumoral tissues, and distant liver metastatic tissues were examined using quantitative real-time PCR, western blotting, and immunohistochemistry staining. The log-rank test and Cox regression model were used to analyze the relationship between AOC1 expression and prognosis. Proliferation assays (Cell Counting Kit‐8 and colony formation assays), migration assays (Transwell and wound healing assays) and xenograft tumor formation in nude mice were performed to assess the biological role of AOC1 in CRC cells.Results AOC1 expression significantly increased in human CRC tissues, especially in liver metastases, and was associated with a worse prognosis. In addition, AOC1 had higher expression in tumor organoids than in normal organoids, suggesting that it was highly expressed in the tumor epithelium. Functional analysis demonstrated that AOC1 knockdown inhibited the proliferation and migration of CRC cells by inducing EMT in vitro. Xenograft tumor formation in nude mice showed that knockdown of AOC1 inhibited the tumor xenografts growth in vivo.ConclusionHigh expression of AOC1 was significantly associated with worse clinical outcomes, was an independent risk factor for poor prognosis, and promoted aggressive CRC cell phenotypes. AOC1 is expected to become a novel biomarker for predicting the prognosis of patients with CRC and an effective therapeutic target in clinical practice.
Highlights
Colorectal cancer (CRC) is the second most common malignant tumor, with the fourth highest mortality rate
Amine oxidase copper containing 1 (AOC1) is expected to become a novel biomarker for predicting the prognosis of patients with CRC and an effective therapeutic target in clinical practice
Immunohistochemistry (IHC) was performed on 192 CRC tumor tissues and paired adjacent normal colon tissues from Xinhua Hospital in tissue microarray (TMA), and 41 patients were excluded from further analysis as they were lost to follow-up
Summary
Colorectal cancer (CRC) is the second most common malignant tumor, with the fourth highest mortality rate. In the past 20 years, the incidence rate of CRC has increased significantly, especially in larger cities, and there has been a trend of younger disease [2, 3]. Despite advancements in treatment in the past few decades, the mortality rate of CRC is still high, mainly due to recurrence and distant organ metastasis [4]. Some diagnostic biomarkers, such as CEA and CA199 [7], are established, it is still necessary to explore new molecules to accurately predict the prognosis of CRC patients and become effective therapeutic targets in clinical practice. Amine oxidase copper containing 1 (AOC1) is a gene whose biological function in colorectal cancer (CRC) has not been elucidated. The purpose of this study was to investigate the clinical significance of AOC1 expression in CRC and its biological function in CRC cell lines
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