Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
4HF Biotec, Freiburg, Germany.
Pathobiology. 2023;90(6):400-408. doi: 10.1159/000531175. Epub 2023 Jul 18.
The clinical course of prostate cancer (PCa) is highly variable, ranging from indolent behavior to rapid metastatic progression. The Gleason score is widely accepted as the primary histologic assessment tool with significant prognostic value. However, additional biomarkers are required to better stratify patients, particularly those at intermediate risk.
In this study, we analyzed the expression of 86 cancer hallmark genes in 171 patients with PCa who underwent radical prostatectomy and focused on the outcome of the 137 patients with postoperative R0-PSA0 status.
Low expression of the IGF1 and SRD52A, and high expression of TIMP2, PLAUR, S100A2, and CANX genes were associated with biochemical recurrence (BR), defined as an increase of prostate-specific antigen above 0.2 ng/mL. Furthermore, the analysis of the expression of 462 noncoding RNAs (ncRNA) in a sub-cohort of 39 patients with Gleason score 7 tumors revealed that high levels of expression of the ncRNAs LINC00624, LINC00593, LINC00482, and cd27-AS1 were significantly associated with BR. Our findings provide further evidence for tumor-promoting roles of ncRNAs in PCa patients at intermediate risk. The strong correlation between expression of LINC00624 and KRT8 gene, encoding a well-known cell surface protein present in PCa, further supports a potential contribution of this ncRNA to PCa progression.
While larger and further studies are needed to define the role of these genes/ncRNA in PCa, our findings pave the way toward the identification of a subgroup of patients at intermediate risk who may benefit from adjuvant treatments and new therapeutic agents.
前列腺癌（PCa）的临床病程变化较大，从惰性表现到快速转移进展均有。Gleason 评分被广泛认为是具有重要预后价值的主要组织学评估工具。然而，需要额外的生物标志物来更好地分层患者，特别是那些处于中危风险的患者。
在这项研究中，我们分析了 171 例接受根治性前列腺切除术的 PCa 患者的 86 个癌症标志基因的表达情况，并重点关注了术后 R0-PSA0 状态的 137 例患者的结局。
IGF1 和 SRD52A 低表达，TIMP2、PLAUR、S100A2 和 CANX 基因高表达与生化复发（BR）相关，BR 定义为前列腺特异性抗原（PSA）升高至 0.2 ng/ml 以上。此外，在一个包含 39 例 Gleason 评分 7 肿瘤患者的亚队列中分析 462 种非编码 RNA（ncRNA）的表达情况表明，ncRNA LINC00624、LINC00593、LINC00482 和 cd27-AS1 的高水平表达与 BR 显著相关。我们的研究结果为中间风险 PCa 患者中 ncRNA 促进肿瘤生长的作用提供了进一步的证据。LINC00624 的表达与编码 PCa 中已知细胞表面蛋白 KRT8 基因之间的强相关性进一步支持了该 ncRNA对 PCa 进展的潜在贡献。
虽然需要更大规模和进一步的研究来确定这些基因/ncRNA 在 PCa 中的作用，但我们的研究结果为确定中间风险患者中的亚组，这些患者可能受益于辅助治疗和新的治疗药物铺平了道路。
