Comprehensive Analysis of SLC35A2 in Pan-Cancer and Validation of Its Role in Breast Cancer

Abstract

Purpose

Elucidation of the oncogenic role of SLC35A2 in human tumors and the potential function and clinical significance in breast cancer.

Methods

Pan-cancer analysis was performed via various bioinformatics tools to explain the pathogenic role of SLC35A2. A prognostic nomogram was also developed based on the SLC35A2 expression and clinicopathological characteristics in breast cancer patients. In addition, the role of SLC35A2 was validated in breast cancer by in vivo and in vitro experiments.

Results

SLC35A2 expression is increased in 27 tumor types, and its high expression is substantially correlated with poor prognosis in patients with a variety of cancers. Receiver operating characteristic (ROC) curves showed that SLC35A2 expression levels could accurately distinguish most tumor tissues from normal tissues. High SLC35A2 expression was linked to increased immune infiltration in myeloid-derived suppressor cells (MDSC), as well as immune checkpoints, ferroptosis-related genes, tumor mutational burden (TMB), and microsatellite instability (MSI). SLC35A2 may be involved in tumorigenesis by regulating the glycosylation process. Furthermore, multivariate Cox analysis showed that SLC35A2 was an independent prognostic factor for breast cancer. And the nomogram model had good predictive accuracy for the prognosis of breast cancer patients. Meanwhile, cellular experiments demonstrated that knockdown of SLC35A2 could significantly inhibit the proliferation, migration and invasion of breast cancer cells, while increasing the protein level of E-cadherin and decreasing N-cadherin. A nude mouse xenograft model showed that inhibition of SLA35A2 expression could significantly inhibit tumor growth.

Conclusion

SLC35A2 has good diagnostic and prognostic values in multiple cancers and is closely related to tumor immune infiltration. In addition, SLA35A2 as an oncogene in breast cancer may be involved in the progression of epithelial mesenchymal transition (EMT).

Keywords:

• SLC35A2
• pan-cancer
• breast cancer
• prognostic
• tumor microenvironment
• EMT

Data Sharing Statement

The data presented in this study are available on request from the corresponding author.

Ethics Statement

The study was conducted by the Declaration of Helsinki, informed consent was obtained from patients, and approved by the Medical Ethics Committee of the First Affiliated Hospital of Anhui Medical University (approval number: 5101389). All animal experiments were approved and conducted under the supervision of the Laboratory Animal Ethics Committee of Anhui Medical University (approval number: LLSC20231253). The use of the cell lines was approved by the Medical Ethics Committee of the First Affiliated Hospital of Anhui Medical University (approval number: 2023494).

Acknowledgments

We thank the contributors to the TCGA database and the authors involved for sharing their data in the open database.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflict of interest.

Additional information

Funding

This research was funded by the Health Commission of Anhui Province (AHWJ2022a001) and the Department of Science and Technology of Anhui Province(202204295107020016).