University Hospital Würzburg, Department of Internal Medicine I, Division of Endocrinology and Diabetology, Würzburg, Germany.
University Hospital Würzburg, Department of Urology and Pediatric Urology, Würzburg, Germany.
Prostate Cancer Prostatic Dis. 2022 Sep;25(3):484-490. doi: 10.1038/s41391-021-00431-3. Epub 2021 Jul 29.
Prostate cancer (PCa) is the most frequent cancer in men. The prognosis of PCa is heterogeneous with many clinically indolent tumors and rare highly aggressive cases. Reliable tissue markers of prognosis are lacking. Active cholesteryl ester synthesis has been associated with prostate cancer aggressiveness. Sterol-O-Acyl transferases (SOAT) 1 and 2 catalyze cholesterol esterification in humans.
To investigate the value of SOAT1 and SOAT2 tissue expression as prognostic markers in high risk PCa.
Formalin-fixed paraffin-embedded tissue samples from 305 high risk PCa cases treated with radical prostatectomy were analyzed for SOAT1 and SOAT2 protein expression by semi-quantitative immunohistochemistry. The Kaplan-Meier method and Cox proportional hazards modeling were used to compare outcome.
Biochemical recurrence (BCR) free survival.
SOAT1 expression was high in 73 (25%) and low in 219 (75%; not evaluable: 13) tumors. SOAT2 was highly expressed in 40 (14%) and at low levels in 249 (86%) samples (not evaluable: 16). By Kaplan-Meier analysis, we found significantly shorter median BCR free survival of 93 months (95% confidence interval 23.6-123.1) in patients with high SOAT1 vs. 134 months (112.6-220.2, Log-rank p < 0.001) with low SOAT1. SOAT2 expression was not significantly associated with BCR. After adjustment for age, preoperative PSA, tumor stage, Gleason score, resection status, lymph node involvement and year of surgery, high SOAT1 but not SOAT2 expression was associated with shorter BCR free survival with a hazard ratio of 2.40 (95% CI 1.57-3.68, p < 0.001). Time to clinical recurrence and overall survival were not significantly associated with SOAT1 and SOAT2 expression CONCLUSIONS: SOAT1 expression is strongly associated with BCR free survival alone and after multivariable adjustment in high risk PCa. SOAT1 may serve as a histologic marker of prognosis and holds promise as a future treatment target.
前列腺癌（PCa）是男性最常见的癌症。PCa 的预后存在异质性，许多临床惰性肿瘤和罕见的高度侵袭性病例。目前缺乏可靠的组织预后标志物。活性胆固醇酯合成与前列腺癌侵袭性有关。固醇-O-酰基转移酶（SOAT）1 和 2 在人类中催化胆固醇酯化。
研究 SOAT1 和 SOAT2 组织表达作为高危 PCa 预后标志物的价值。
对 305 例接受根治性前列腺切除术治疗的高危 PCa 病例的福尔马林固定石蜡包埋组织样本进行 SOAT1 和 SOAT2 蛋白表达的半定量免疫组织化学分析。采用 Kaplan-Meier 法和 Cox 比例风险模型比较结果。
生化复发（BCR）无复发生存率。
SOAT1 表达高的肿瘤有 73 例（25%），表达低的肿瘤有 219 例（75%；无法评估：13 例）。SOAT2 高表达的肿瘤有 40 例（14%），低表达的肿瘤有 249 例（86%）（无法评估：16 例）。通过 Kaplan-Meier 分析，我们发现 SOAT1 高表达的患者中位 BCR 无复发生存率为 93 个月（95%置信区间 23.6-123.1），而 SOAT1 低表达的患者中位 BCR 无复发生存率为 134 个月（112.6-220.2，Log-rank p<0.001）。SOAT2 表达与 BCR 无显著相关性。经年龄、术前 PSA、肿瘤分期、Gleason 评分、切除状态、淋巴结受累和手术年份调整后，高 SOAT1 表达而非 SOAT2 表达与较短的 BCR 无复发生存率相关，风险比为 2.40（95%CI 1.57-3.68，p<0.001）。临床复发时间和总生存时间与 SOAT1 和 SOAT2 表达无显著相关性。
SOAT1 表达与高危 PCa 的 BCR 无复发生存率密切相关，且在多变量调整后仍具有显著相关性。SOAT1 可能作为预后的组织标志物，并有望成为未来的治疗靶点。
