PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy

by Selleckchem | Jan 20 2024

Background: Pancreatic adenocarcinoma (PAAD) is an aggressive solid tumour characterised by few early symptoms, high mortality, and lack of effective treatment. Therefore, it is important to identify new potential therapeutic targets and prognostic biomarkers of PAAD.

Methods: The Cancer Genome Atlas and Genotype-Tissue Expression databases were used to identify the expression and prognostic model of protocadherin 1 (PCDH1). The prognostic performance of risk factors and diagnosis of patients with PAAD were evaluated by regression analysis, nomogram, and receiver operating characteristic curve. Paraffin sections were collected from patients for immunohistochemistry (IHC) analysis. The expression of PCDH1 in cells obtained from primary tumours or metastatic biopsies was identified using single-cell RNA sequencing (scRNA-seq). Real-time quantitative polymerase chain reaction (qPCR) and western blotting were used to verify PCDH1 expression levels and the inhibitory effects of the compounds.

Results: The RNA and protein levels of PCDH1 were significantly higher in PAAD cells than in normal pancreatic ductal cells, similar to those observed in tissue sections from patients with PAAD. Aberrant methylation of the CpG site cg19767205 and micro-RNA (miRNA) hsa-miR-124-1 may be important reasons for the high PCDH1 expression in PAAD. Up-regulated PCDH1 promotes pancreatic cancer cell metastasis. The RNA levels of PCDH1 were significantly down-regulated following flutamide treatment. Flutamide reduced the percentage of PCDH1 RNA level in PAAD cells Panc-0813 to < 50%. In addition, the PCDH1 protein was significantly down-regulated after Panc-0813 cells were incubated with 20 µM flutamide and proves to be a potential therapeutic intervention for PAAD.

Conclusion: PCDH1 is a key prognostic biomarker and promoter of PAAD metastasis. Additionally, flutamide may serve as a novel compound that down-regulates PCDH1 expression as a potential treatment for combating PAAD progression and metastasis.

Comments:

This study seems to highlight the potential significance of protocadherin 1 (PCDH1) as both a prognostic biomarker and a promoter of metastasis in pancreatic adenocarcinoma (PAAD). The findings suggest that the high expression of PCDH1 in PAAD cells, attributed partly to aberrant methylation and micro-RNA regulation, contributes to the aggressive nature of the disease.

The identification of flutamide as a potential intervention that down-regulates PCDH1 expression is intriguing. By reducing PCDH1 levels, flutamide shows promise as a therapeutic approach to combatting PAAD progression and metastasis.The use of multiple methodologies such as RNA sequencing, immunohistochemistry, and molecular analyses like PCR and western blotting to validate the findings lends credibility to the study's conclusions. Moreover, the utilization of databases like The Cancer Genome Atlas and Genotype-Tissue Expression strengthens the analysis by incorporating a broad range of data.

However, further research and clinical trials will be crucial to confirm the efficacy and safety of flutamide as a treatment for PAAD. Additionally, exploring the specific mechanisms by which PCDH1 promotes metastasis could uncover potential targeted therapies against this aggressive cancer.