Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Hum Pathol. 2018 Apr;74:92-98. doi: 10.1016/j.humpath.2018.01.009. Epub 2018 Jan 12.
The combined administration of nab-paclitaxel and gemcitabine (nab-P + Gem) is a standard chemotherapy for unresectable pancreatic ductal adenocarcinoma (UR-PDAC); thus, a predictive biomarker to identify patients best suited for nab-P + Gem therapy would be useful. Class III β-tubulin (TUBB3) has been reported to be a predictive marker for taxane resistance in various tumors. However, the correlation between TUBB3 expression and the response to nab-P + Gem in patients with UR-PDAC has not been evaluated. We retrospectively reviewed 75 patients with UR-PDAC who received nab-P + Gem. TUBB3 expression was examined immunohistochemically in specimens obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). From 67 analyzable specimens that were available for TUBB3 staining, 14 (21%) were negative for TUBB3 immunostaining and 53 (79%) were positive. Patients with negative TUBB3 expression showed a significantly higher disease control rate (100% vs. 64.2%; P = .008) and longer progression-free survival (PFS); (7.1 months vs. 3.7 months; log-rank test, P = .036) than those of patients with positive. Furthermore, negative TUBB3 expression was an independent predictive marker of a prolonged PFS on multivariate analysis (hazard ratio, 2.41; 95% confidence interval, 1.11-5.24; P = .026). Our data indicate that an absence of TUBB3 expression in specimens obtained by EUS-FNA may be a favorable predictive marker of the response to nab-P + Gem in patients with UR-PDAC, highlighting its use as a potential new biomarker for treatment optimization.
纳武利尤单抗联合吉西他滨(nab-P + Gem)是治疗不可切除的胰腺导管腺癌(UR-PDAC)的标准化疗方案;因此,识别最适合 nab-P + Gem 治疗的患者的预测性生物标志物将是有用的。III 类β-微管蛋白(TUBB3)已被报道为各种肿瘤中紫杉类耐药的预测标志物。然而,TUBB3 表达与 UR-PDAC 患者对 nab-P + Gem 反应之间的相关性尚未得到评估。我们回顾性分析了 75 例接受 nab-P + Gem 治疗的 UR-PDAC 患者。通过内镜超声引导下细针抽吸(EUS-FNA)获得的标本进行 TUBB3 表达的免疫组织化学检查。在可用于 TUBB3 染色的 67 个可分析标本中,有 14 个(21%)TUBB3 免疫染色阴性,53 个(79%)TUBB3 染色阳性。TUBB3 表达阴性的患者疾病控制率(100%比 64.2%;P =.008)和无进展生存期(PFS)明显更长(7.1 个月比 3.7 个月;log-rank 检验,P =.036)。此外,多变量分析显示,TUBB3 表达阴性是 PFS 延长的独立预测标志物(风险比,2.41;95%置信区间,1.11-5.24;P =.026)。我们的数据表明,EUS-FNA 获得的标本中 TUBB3 表达缺失可能是 UR-PDAC 患者对 nab-P + Gem 反应的有利预测标志物,突出了其作为治疗优化的潜在新生物标志物的用途。