Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China.
Department of Urology, Zhongda Hospital Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China.
Eur J Med Res. 2024 Apr 20;29(1):242. doi: 10.1186/s40001-024-01818-3.
The metastasis and aggressive nature of prostate cancer (PCa) has become a major malignancy related threat that concerns men's health. The efficacy of immune monotherapy against PCa is questionable due to its lymphocyte-suppressive nature.
Endoplasmic reticulum stress- (ERS-) and PCa-prognosis-related genes were obtained from the Molecular Signatures Database and the Cancer Genome Atlas database. The expression, prognosis and immune infiltration values of key genes were explored by "survival R package", "rms", "xCELL algorithm", and univariate-multivariate Cox and LASSO regression analyses. The "consensus cluster plus R package" was used for cluster analysis.
As ERS-related genes, ERLIN2 and CDK5RAP3 showed significant expressional, prognostic and clinic-pathologic values. They were defined as the key genes significantly correlated with immune infiltration and response. The nomogram was constructed with T-stage and primary treatment outcome, and the risk-prognostic model was constructed in the following way: Riskscore = (- 0.1918) * ERLIN2 + (0.5254) * CDK5RAP3. Subsequently, prognostic subgroups based on key genes classified the high-risk group as a pro-cancer subgroup that had lower mutation rates of critical genes (SPOP and MUC16), multiple low-expression immune-relevant molecules, and differences in macrophages (M1 and M2) expressions. Finally, ERLIN2 as an anti-oncogene and CDK5RAP3 as a pro-oncogene were further confirmed by cell phenotype assays and immunohistochemistry.
We identified ERLIN2 and CDK5RAP3 as ERS-related genes with important prognostic and immunologic values, and classified patients between high- and low-risk subgroups, which provided new prognostic markers, immunotherapeutic targets, and basis for prognostic assessments.
前列腺癌（PCa）的转移和侵袭性已成为威胁男性健康的主要恶性肿瘤。由于其淋巴细胞抑制特性，免疫单药治疗对 PCa 的疗效存在疑问。
从分子特征数据库和癌症基因组图谱数据库中获取内质网应激（ERS）和与 PCa 预后相关的基因。通过“生存 R 包”、“rms”、“xCELL 算法”以及单变量-多变量 Cox 和 LASSO 回归分析，探讨关键基因的表达、预后和免疫浸润值。使用“共识聚类加 R 包”进行聚类分析。
作为 ERS 相关基因，ERLIN2 和 CDK5RAP3 表现出显著的表达、预后和临床病理价值。它们被定义为与免疫浸润和反应显著相关的关键基因。使用 T 分期和主要治疗结果构建了列线图，并通过以下方法构建了风险预后模型：Riskscore=（-0.1918）* ERLIN2+（0.5254）* CDK5RAP3。随后，基于关键基因的风险预测模型将患者分为高危组和低危组，其中高危组为促癌亚组，其关键基因（SPOP 和 MUC16）突变率较低，多种免疫相关低表达分子，以及巨噬细胞（M1 和 M2）表达存在差异。最后，通过细胞表型分析和免疫组化进一步证实了 ERLIN2 作为抑癌基因和 CDK5RAP3 作为原癌基因的作用。
我们确定 ERLIN2 和 CDK5RAP3 为具有重要预后和免疫价值的 ERS 相关基因，并将患者分为高风险和低风险亚组，为预后评估提供了新的预后标志物、免疫治疗靶点和依据。
