Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología de Colombia, Bogotá, DC, Colombia.
Programa de doctorado en Ciencias Biológicas, Pontificia Universidad Javeriana, Bogotá, DC, Colombia.
Cancer Med. 2023 Feb;12(4):4306-4320. doi: 10.1002/cam4.5301. Epub 2022 Nov 3.
The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients.
RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERG /ERG tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERG and ERG tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed to evaluate biochemical recurrence (BCR)-free survival.
The identification of 150 DEGs between ERG and ERG tumors revealed clustering of most of the non-BCR cases (60%) into de ERG group and most of the BCR cases (60.8%) in ERG group. Kaplan-Meier survival curves showed a worst BCR-free survival for ERG patients, and a significant reduced risk of BCR was observed for ERG cases (OR = 0.29 (95%CI, 0.10-0.8)). Enrichment pathway analysis identified metabolic-related pathways, such as the renin-angiotensin system and angiotensin maturation system, the linoleic acid metabolism, and polyamines metabolism in these ERG groups.
ERG tumor cases were associated with poor BCR-free survival in our Hispanic/Latino patients, with metabolism-related pathways altered in the BCR progression.
Our findings suggest the need to dissect the role of diet, metabolism, and lifestyle as risk factors for more aggressive PCa subtypes.
ERG 状态分子亚分型在前列腺癌（PCa）预后中的作用仍存在争议。在这项研究中，我们根据 ERG 状态鉴定差异表达基因（DEGs），以探讨其在西班牙裔/拉丁裔 PCa 患者预后中的富集途径和意义。
从 78 例接受根治性前列腺切除术（RP）的西班牙裔 PCa 组织中提取 RNA 进行 RNA-seq。根据非肿瘤样本中 1.5 倍中位数表达，确定 ERG/ERG 肿瘤组。在 ERG 和 ERG 肿瘤之间，筛选 FDR<0.01 和倍数变化>2 的差异表达基因（DEGs），并将其提交到 MetaCore 进行富集分析。进行生存和相关性分析以评估生化复发（BCR）无复发生存。
在 ERG 和 ERG 肿瘤之间鉴定出 150 个 DEGs，大多数非 BCR 病例（60%）聚类到 de ERG 组，大多数 BCR 病例（60.8%）聚类到 ERG 组。Kaplan-Meier 生存曲线显示 ERG 患者 BCR 无复发生存最差，ERG 病例 BCR 风险显著降低（OR=0.29（95%CI，0.10-0.8））。富集途径分析确定了代谢相关途径，如肾素-血管紧张素系统和血管紧张素成熟系统、亚油酸代谢和多胺代谢在这些 ERG 组中发生改变。
在我们的西班牙裔/拉丁裔患者中，ERG 肿瘤病例与较差的 BCR 无复发生存相关，在 BCR 进展过程中改变了与代谢相关的途径。
我们的研究结果表明，需要剖析饮食、代谢和生活方式作为更具侵袭性的 PCa 亚型的危险因素的作用。
