KEY TAKEAWAYS
- The study aimed to investigate the prognostic and immunogenic significance of endoplasmic reticulum stress-related genes in PCa progression and treatment response.
- Researchers noticed that ERLIN2 and CDK5RAP3 show vital prognostic and immunotherapeutic roles in PCa, improving patient stratification and treatment outcomes.
The metastasis and aggressive nature of prostate cancer (PCa) pose significant health concerns for men. However, the efficacy of immune monotherapy against PCa is questionable due to its lymphocyte-suppressive nature.
Lilin Wan and the team aimed to assess immune monotherapy efficacy for PCa considering its metastasis and lymphocyte-suppressive nature.
They performed an inclusive analysis utilizing endoplasmic reticulum stress (ERS)- and PCa-prognosis-related genes obtained from the Molecular Signatures Database and the Cancer Genome Atlas database. Expression, prognosis, and immune infiltration values of key genes were explored through the “survival R package,” “rms,” “xCELL algorithm,” and univariate-multivariate Cox and LASSO regression analyses. Additionally, the “consensus cluster plus R package” facilitated cluster analysis.
The ERS-related genes, ERLIN2 and CDK5RAP3, manifested significant expressional, prognostic, and clinic-pathologic values. They emerged as key genes strongly correlated with immune infiltration and response. A nomogram incorporating T-stage and primary treatment outcome was constructed alongside a risk-prognostic model: Riskscore = (-0.1918) * ERLIN2 + (0.5254) * CDK5RAP3.
Subsequent classification based on these key genes delineated a high-risk subgroup exhibiting pro-cancer characteristics, including lower mutation rates of critical genes (SPOP and MUC16), multiple low-expression immune-relevant molecules, and distinct macrophage (M1 and M2) expressions. Further validation through cell phenotype assays and immunohistochemistry confirmed ERLIN2 as an anti-oncogene and CDK5RAP3 as a pro-oncogene.
The study identified ERLIN2 and CDK5RAP3 as crucial ERS-related genes with significant prognostic and immunologic implications. By classifying patients into high- and low-risk subgroups, novel prognostic markers and immunotherapeutic targets were unveiled, laying a foundation for improved prognostic assessments in PCa.
The study was sponsored by the Changzhou Health Commission Project.
Source: https://pubmed.ncbi.nlm.nih.gov/38643190/
Wan L, Fan Y, Wu T, et al. (2024) “Endoplasmic reticulum stress-related genes as prognostic and immunogenic biomarkers in prostate cancer. Eur J Med Res. 2024 Apr 20;29(1):242. doi: 10.1186/s40001-024-01818-3. PMID: 38643190; PMCID: PMC11031923.
