Vos Larissa J, Yusuf Dimas, Lui Arthur, Abdelaziz Zainab, Ghosh Sunita, Spratlin Jennifer L, Mackey John R
JCO Precis Oncol. 2019 Dec;3:1-22. doi: 10.1200/PO.18.00240.
Gemcitabine, the primary drug for the treatment of pancreatobiliary cancer (PBC), requires human equilibrative nucleoside transporter 1 (hENT1) to enter cells. High tumoral hENT1 expression has been linked with improved survival among patients with PBC treated with gemcitabine; however, this finding has been inconsistent, and studies used different expression assays.
Databases were reviewed for studies that examined hENT1 and clinical outcome in PBC. Of 307 publications, 34 studies were found that used immunohistochemistry (IHC) with one of eight anti-hENT1 antibody assays. Five studies were excluded for redundancy, and 29 studies underwent detailed review.
On average, 51% of tumor samples had high hENT1 expression (range, 7% to 92%). Among studies that examined hENT1 expression and overall survival (OS), 58% (15 of 26 studies) showed an association between high tumoral hENT1 and improved OS for gemcitabine-treated patients. Among 10D7G2 antibody studies, 88% (seven of eight studies) demonstrated this association. Studies with other antibodies-in particular, SP120 (two of nine studies)-were less consistent. The ability to detect an association between improved OS and high hENT1 was antibody dependent (χ = .0237). An association between high tumoral hENT1 expression and improved disease-free/progression-free survival (DFS/PFS) was demonstrated in 71% of studies (15 of 21 studies). Pooled hazard ratio (HR) analyses of all antibody studies demonstrated a link between high hENT1 tumor expression and improved OS (HR, 0.674; 95% CI, 0.509 to 0.893; = .006) and DFS/PFS (HR, 0.740; 95% CI, 0.517 to 0.1.059; = .10). This signal was stronger among studies that used the 10D7G2 antibody in comparison to those in which another antibody was used, with HRs of 0.488 (95% CI, 0.396 to 0.602; < .001) and 0.410 (95% CI, 0.280 to 0.599; < .001), respectively.
High tumoral hENT1 expression on IHC with 10D7G2 is a strong and reproducible prognostic marker for improved outcome among gemcitabine-treated patients with PBC.
吉西他滨是治疗胰腺胆管癌（PBC）的主要药物，其进入细胞需要人平衡核苷转运体1（hENT1）。肿瘤中hENT1高表达与接受吉西他滨治疗的PBC患者生存率提高相关；然而，这一发现并不一致，且各项研究使用的表达检测方法不同。
检索数据库中有关检测PBC患者hENT1与临床结局的研究。在307篇出版物中，发现34项研究使用了免疫组织化学（IHC）及8种抗hENT1抗体检测方法之一。排除5项重复研究，对29项研究进行详细审查。
肿瘤样本平均51%有hENT1高表达（范围7%至92%）。在检测hENT1表达与总生存期（OS）的研究中，58%（26项研究中的15项）显示肿瘤hENT1高表达与接受吉西他滨治疗患者的OS改善相关。在10D7G2抗体研究中，88%（8项研究中的7项）证实了这种相关性。使用其他抗体的研究——特别是SP120（9项研究中的2项）——一致性较差。检测OS改善与hENT1高表达之间相关性的能力取决于抗体（χ = 0.0237）。71%的研究（21项研究中的15项）证实肿瘤hENT1高表达与无病生存期/无进展生存期（DFS/PFS）改善相关。对所有抗体研究进行汇总风险比（HR）分析，结果显示hENT1肿瘤高表达与OS改善（HR，0.674；95%CI，0.509至0.893；P = 0.006）及DFS/PFS改善（HR，0.740；95%CI，0.517至1.059；P = 0.10）之间存在关联。与使用其他抗体的研究相比，使用10D7G2抗体的研究中这种关联更强，HR分别为0.488（95%CI，0.396至0.602；P < 0.001）和0.410（95%CI，0.280至0.599；P < 0.001）。
采用10D7G2进行免疫组化检测时，肿瘤hENT1高表达是接受吉西他滨治疗PBC患者预后改善的一个强大且可重复的预后标志物。
