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Upregulation of NPC1 and its association with poor prognosis in gastric cancer

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Abstract

Background

The Niemann–Pick disease type C1 (NPC1) protein plays a pivotal role in lipid transport, particularly free cholesterol, within lysosomal/late endosomal membranes. Previous studies have highlighted NPC1 as a promising target for cholesterol trafficking and cancer therapy. Nevertheless, the expression of NPC1 in gastric cancer (GC) and its clinical implications remain unexplored. This study aims to investigate NPC1 expression in GC and its correlation with patient prognosis.

Methods

NPC1 expression levels in GC and normal tissues were assessed using the GEPIA database, and survival analysis was conducted via Kaplan‒Meier Plotter. Evaluation of potential biological effects of NPC1 in GC by protein–protein interaction network and GO, KEGG bioenrichment analysis. Immunohistochemistry was performed on surgical samples collected from 306 GC patients. Correlations between NPC1 expression, clinical characteristics, and patient prognosis were analyzed.

Results

NPC1 mRNA expression was elevated in GC tissues compared to normal tissues (P < 0.05) and significantly associated with poorer prognosis. In our cohort of 306 patients, NPC1 exhibited significant upregulation in GC versus adjacent normal tissues (P = 0.031). High NPC1 expression correlated with adverse clinical characteristics, including lymph node metastasis, distant metastasis, and advanced TNM stage (all P < 0.05). Patients with high NPC1 expression experienced notably shorter overall survival (P < 0.001), particularly in stages III and IV (P = 0.003). Multivariate Cox regression analysis identified high NPC1 expression as an independent prognostic factor for GC patients (HR 1.57, 95% CI 1.14–2.18, P = 0.006). Lastly, an optimized nomogram incorporating NPC1, tumor size, and TNM stage was constructed.

Conclusions

NPC1 expression is upregulated in GC and serves as a pivotal prognostic factor for adverse outcomes in GC patients.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No. 81802342), Guangzhou Municipal Science and Technology Project (Grant No. 2023A04J2208) and Kelin New Star of the First Affiliated Hospital of Sun Yat‐sen University (Grant No. R08010). The authors expressed high respect to the patients who provided clinical samples for this study.

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Author notes

  1. Wei Tang, Jiahua Huang, and Guanghua Li have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou, 510080, Guangdong, China

    Wei Tang, Jiahua Huang, Guanghua Li, Zhihao Zhou & Zhixiong Wang

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  1. Wei Tang
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  3. Guanghua Li
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Contributions

Conceptualization, Zhixiong Wang and Guanghua Li; methodology, Zhixiong Wang; software, Jiahua Huang and Wei Tang; validation, Wei Tang; investigation, Jiahua Huang; resources, Zhihao Zhou and Zhixiong Wang; data curation, Jiahua Huang; writing—original draft preparation, Wei Tang and Jiahua Huang; writing—review and editing, Zhixiong Wang; visualization, Wei Tang; funding acquisition, Zhixiong Wang. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Zhixiong Wang.

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The authors declare no potential conflicts of interest.

Ethical approval

The study was reviewed and approved by the Ethics Committee for Clinical Research and Animal Trials of the First Affiliated Hospital of Sun Yat-sen University (Approval No. [2022]715).

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Informed consent was obtained from all subjects involved in the study.

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Tang, W., Huang, J., Li, G. et al. Upregulation of NPC1 and its association with poor prognosis in gastric cancer. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03490-9

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