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Targeting SEZ6L2 in Colon Cancer: Efficacy of Bexarotene and Implications for Survival

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Abstract

Background

Bexarotene, also recognized as Targretin, is categorized as a retinoid, a type of cancer drug. Nevertheless, the precise mechanisms of bexarotene in relation to colon cancer remain unclear. In colon cancer, SEZ6L2 was suggested as one of the biomarkers and targets. This study presents a comprehensive exploration of the role of SEZ6L2 in colon cancer.

Methods

We utilized both TCGA data and a cohort of Chinese patients. In a meticulous analysis of 478 colon cancer cases, SEZ6L2 expression levels were examined in relation to clinical characteristics, staging parameters, and treatment outcomes. Additionally, we investigated the pharmacological impact of bexarotene on SEZ6L2, demonstrating a significant downregulation of SEZ6L2 at both mRNA and protein levels in colon cancer patients following bexarotene treatment.

Results

SEZ6L2 consistently overexpresses in colon cancer, serving as a potential universal biomarker with prognostic significance, validated in a diverse Chinese cohort. In vitro, SEZ6L2 promotes cell viability without affecting migration. Bexarotene treatment inhibits SEZ6L2 expression, correlating with reduced viability both in vitro and in vivo. SEZ6L2 overexpression accelerates declining survival rates in an in vivo context. Bexarotene’s efficacy is context-dependent, effective in parental cells but not with SEZ6L2 overexpression. Computational predictions suggest a direct SEZ6L2-bexarotene interaction, warranting further experimental exploration.

Conclusion

The study provides valuable insights into SEZ6L2 as a prognostic biomarker in colon cancer, revealing its intricate relationship with clinical parameters, treatment outcomes, and bexarotene effects. Context-dependent therapeutic responses emphasize the nuanced understanding required for SEZ6L2’s role in colon cancer, paving the way for targeted therapeutic strategies.

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Data Availability

No datasets were generated or analysed during the current study.

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Funding

This work is supported by The Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine.

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Author notes

  1. Huajun Zheng and Jianying Zheng contributed equally to this work.

Authors and Affiliations

  1. Digestive System Department, The Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, 318 Chaowang Road, Gongshu District, Hangzhou City, Zhejiang Province, China

    Huajun Zheng & Yan Shen

  2. Operation Department, The Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, Hangzhou City, Zhejiang Province, China

    Jianying Zheng

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  1. Huajun Zheng
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  2. Jianying Zheng
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Contributions

Huajun Zheng and Jianying Zheng contributed equally to this work. Huajun Zheng and Jianying Zheng conceptualized the project; Huajun Zheng was responsible for the material preparation and characterization; Huajun Zheng, Jianying Zheng, and Yan Shen conducted the in vitro experiments; Jianying Zheng performed experiments in vivo; Yan Shen performed bioinformatic analysis and provided guidance on experimental design and wrote the manuscript.

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Correspondence to Huajun Zheng.

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Zheng, H., Zheng, J. & Shen, Y. Targeting SEZ6L2 in Colon Cancer: Efficacy of Bexarotene and Implications for Survival. J Gastrointest Canc (2024). https://doi.org/10.1007/s12029-024-01085-9

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