Department of Surgical Gastroenterology and Transplantation, Copenhagen University Hospital, C 2-12-2, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
World J Surg. 2012 Nov;36(11):2699-707. doi: 10.1007/s00268-012-1705-y.
The aim of the present study was to identify a panel of microRNAs (miRNAs) that can predict overall survival (OS) in non micro-dissected cancer tissues from patients operated for pancreatic cancer (PC).
MiRNAs were purified from formalin-fixed paraffin embedded (FFPE) cancer tissue from 225 patients operated for PC. Only a few of those patients received adjuvant chemotherapy. Expressions of miRNAs were determined with the TaqMan MicroRNA Array v2.0. Two statistical methods, univariate selection and the Lasso (Least Absolute Shrinkage and Selection Operator) method, were applied in conjunction with the Cox proportional hazard model to relate miRNAs to OS.
High expression of miR-212 and miR-675 and low expression of miR-148a, miR-187, and let-7g predicted short OS independent of age, gender, calendar year of operation, KRAS mutation status, tumor stage, American Society of Anesthesiologists (ASA) score, localization (not miR-148a), and differentiation of tumor. A prognostic index (PI) based on these five miRNAs was calculated for each patient. The median survival was 1.09 years (Confidence Interval [CI] 0.98-1.43) for PI > median PI compared to 2.23 years (CI 1.84-4.36) for PI < median. MiR-212, miR-675, miR-187, miR-205, miR-944, miR-431, miR-194, miR-148a, and miR-769-5p showed the strongest prediction ability by the Lasso method. Thus miR-212, miR-675, miR-187, and miR-148a were predictors for OS in both statistical methods.
The combination of five miRNAs expression in non micro-dissected FFPE PC tissue can identify patients with short OS after radical surgery. The results are independent of chemotherapy treatment. Patients with a prognostic index > median had a very short median OS of only 1 year.
本研究的目的是鉴定一组能够预测非微切割胰腺癌患者手术切除后总生存期（OS）的 microRNAs（miRNAs）。
从 225 名接受胰腺癌手术的患者的福尔马林固定石蜡包埋（FFPE）癌组织中纯化 miRNAs。只有少数患者接受了辅助化疗。使用 TaqMan MicroRNA Array v2.0 测定 miRNAs 的表达。应用单变量选择和 Lasso（最小绝对收缩和选择算子）方法与 Cox 比例风险模型相结合，将 miRNAs 与 OS 相关联。
miR-212 和 miR-675 的高表达以及 miR-148a、miR-187 和 let-7g 的低表达与 OS 短独立于年龄、性别、手术年份、KRAS 突变状态、肿瘤分期、美国麻醉师协会（ASA）评分、肿瘤定位（非 miR-148a）和分化。为每位患者计算了基于这五个 miRNAs 的预后指数（PI）。PI > 中位数的中位生存期为 1.09 年（95%CI 0.98-1.43），PI < 中位数的中位生存期为 2.23 年（95%CI 1.84-4.36）。Lasso 法显示 miR-212、miR-675、miR-187、miR-205、miR-944、miR-431、miR-194、miR-148a 和 miR-769-5p 具有最强的预测能力。因此，miR-212、miR-675、miR-187 和 miR-148a 是两种统计学方法中 OS 的预测因子。
非微切割 FFPE PC 组织中五个 miRNAs 表达的组合可识别根治性手术后 OS 短的患者。结果独立于化疗治疗。PI > 中位数的患者中位 OS 非常短，仅为 1 年。
