Open Access

LTBP2 inhibits prostate cancer progression and metastasis via the PI3K/AKT signaling pathway

  • Authors:
    • Xiaowen Zhang
    • Chuanjie Tian
    • Jianbin Cheng
    • Weipu Mao
    • Menglan Li
    • Ming Chen
  • View Affiliations

  • Published online on: July 8, 2022     https://doi.org/10.3892/etm.2022.11500
  • Article Number: 563
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Biochemical recurrence (BCR) is a cause of concern in advanced prostate cancer (PCa). Thus, novel diagnostic biomarkers are required to improve clinical care. However, research on PCa immunotherapy is also scarce. Hence, the present study aimed to explore promising BCR‑related diagnostic biomarkers, and their expression pattern, prognostic value, immune response effects, biological functions, and possible molecular mechanisms were evaluated. GEO datasets (GSE46602, GSE70768, and GSE116918) were downloaded and merged as the training cohort, and differential expression analysis was performed. Lasso regression and SVM‑RFE algorithm, as well as PPI analysis and MCODE algorithm, were then applied to filter BCR‑related biomarker genes. The CIBERSORT and estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) methods were used to calculate the fractions of tumor‑­infiltrating immune cells. GO/DO enrichment analyses were used to identify the biological functions. The expression of latent transforming growth factor β‑binding protein 2 (LTBP2) was determined by RT‑qPCR and western blotting. The role of LTBP2 in PCa was determined by CCK‑8, Transwell, and the potential mechanism was investigated by KEGG and GSEA and confirmed by western blotting. In total, 44 BCR‑related differentially expressed genes (DEGs) in the training cohort were screened. LTBP2 was found to be a diagnostic biomarker of BCR in PCa and was associated with CD4+ T‑cell infiltration and response to anti‑PD‑1/PD‑L1 immunotherapy. Subsequently, using the ESTIMATE algorithm, it was identified that LTBP2 was associated with the tumor microenvironment and could be a predictor of the clinical benefit of immune checkpoint blockade. Finally, the expression and biological function of LTBP2 were evaluated via cellular experiments. The results showed that LTBP2 was downregulated in PCa cells and inhibited PCa proliferation and metastasis via the PI3K/AKT signaling pathway in vitro. In conclusion, LTBP2 was a promising diagnostic biomarker of BCR of PCa and had an important role in CD4+ T‑cell recruitment. Moreover, it was associated with immunotherapy in patients with PCa who developed BCR, and it inhibited PCa proliferation and metastasis via the PI3K/AKT signaling pathway in vitro.

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September-2022
Volume 24 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhang X, Tian C, Cheng J, Mao W, Li M and Chen M: LTBP2 inhibits prostate cancer progression and metastasis via the PI3K/AKT signaling pathway. Exp Ther Med 24: 563, 2022
APA
Zhang, X., Tian, C., Cheng, J., Mao, W., Li, M., & Chen, M. (2022). LTBP2 inhibits prostate cancer progression and metastasis via the PI3K/AKT signaling pathway. Experimental and Therapeutic Medicine, 24, 563. https://doi.org/10.3892/etm.2022.11500
MLA
Zhang, X., Tian, C., Cheng, J., Mao, W., Li, M., Chen, M."LTBP2 inhibits prostate cancer progression and metastasis via the PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 24.3 (2022): 563.
Chicago
Zhang, X., Tian, C., Cheng, J., Mao, W., Li, M., Chen, M."LTBP2 inhibits prostate cancer progression and metastasis via the PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 24, no. 3 (2022): 563. https://doi.org/10.3892/etm.2022.11500