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

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 tumorinfiltrating 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.

Disulfidptosis-related genes serve as potential prognostic biomarkers and indicate tumor microenvironment characteristics and immunotherapy response in prostate cancer

“…MYADM is notably overexpressed in African American men who experience biochemical recurrence within 5 years 30 . Zhang et al suggest that LTBP2 is not only a promising diagnostic biomarker for biochemical recurrence of prostate cancer but also plays a significant role in regulating the immune microenvironment, affecting responses to immunotherapy, and inhibiting cancer cell proliferation and metastasis through the PI3K/AKT signaling pathway 31 . PAPSS2, a gene associated with androgen synthesis, is proposed by Ibeawuchi et al to influence the progression of prostate cancer, where its gene deletion is closely linked to an increased risk of postoperative PSA recurrence, positioning PAPSS2 as a potential predictive biomarker for PSA recurrence 32 .…”

Exploration of prognostic biomarkers in head and neck squamous cell carcinoma microenvironment from TCGA database

“…In recent year, algorithms have been developed to predict tumor purity using gene expression data based on the TCGA database. For example, (36,37), breast cancer (38,39), colorectal cancer (40)(41)(42) and hepatocellular carcinoma (43), which demonstrated that such big-data-based algorithms are effective, although its utility on immune and/or stromal scores in glioblastoma multiforme (GBM) has not been explored in detail.…”