Abstract：
BACKGROUND: FOLFIRINOX and gemcitabine-nabpaclitaxel (GnP) are standard first-line treatment regimens for advanced pancreatic ductal adenocarcinoma (PDAC). However, currently, there is a lack of predictive biomarkers to aid in the treatment selection. We aimed to explore the prognostic and predictive value of class III β-Tubulin (TUBB3) and human equilibrative nucleoside transporter 1 (hENT1) expression, which have previously been shown to be associated with taxane and gemcitabine resistance in advanced PDAC.
METHODS: We conducted a retrospective analysis of 106 patients with advanced PDAC treated with GnP and/or FOLFIRINOX at our institution. TUBB3 and hENT1 immunohistochemical staining was performed on tumor specimens and subsequently evaluated based on the intensity and percentage of expression.
RESULTS: In patients who received the GnP regimen, a high combined score (TUBB3low/hENT1high) was associated with a higher DCR and longer PFS compared to those with intermediate (TUBB3high/hENT1high or TUBB3low/hENT1low) and low score (TUBB3high/hENT1low). In the multivariate analysis, a high combined score was an independent predictor of higher DCR (OR:11.96; 95 % CI:2.61-54.82; p = 0.001) and longer PFS (HR:0.33; 95%CI:0.18-0.60; p < 0.001). However, there was no difference in response rates or PFS based on TUBB3 and hENT1 expression among patients receiving the FOLFIRINOX regimen.
CONCLUSIONS: Our findings indicate that tumor TUBB3 and hENT1 expression may predict the efficacy of the GnP regimen, and low TUBB3 and high hENT1 expression (TUBB3low/hENT1high) are associated with a higher DCR and longer PFS in patients treated with GnP. Evaluating TUBB3 and hENT1 jointly can identify the patients most (as well as least) likely to benefit from GnP chemotherapy.
METHODS: We conducted a retrospective analysis of 106 patients with advanced PDAC treated with GnP and/or FOLFIRINOX at our institution. TUBB3 and hENT1 immunohistochemical staining was performed on tumor specimens and subsequently evaluated based on the intensity and percentage of expression.
RESULTS: In patients who received the GnP regimen, a high combined score (TUBB3low/hENT1high) was associated with a higher DCR and longer PFS compared to those with intermediate (TUBB3high/hENT1high or TUBB3low/hENT1low) and low score (TUBB3high/hENT1low). In the multivariate analysis, a high combined score was an independent predictor of higher DCR (OR:11.96; 95 % CI:2.61-54.82; p = 0.001) and longer PFS (HR:0.33; 95%CI:0.18-0.60; p < 0.001). However, there was no difference in response rates or PFS based on TUBB3 and hENT1 expression among patients receiving the FOLFIRINOX regimen.
CONCLUSIONS: Our findings indicate that tumor TUBB3 and hENT1 expression may predict the efficacy of the GnP regimen, and low TUBB3 and high hENT1 expression (TUBB3low/hENT1high) are associated with a higher DCR and longer PFS in patients treated with GnP. Evaluating TUBB3 and hENT1 jointly can identify the patients most (as well as least) likely to benefit from GnP chemotherapy.
摘要：
背景：FOLFIRINOX和吉西他滨-纳巴紫杉醇（GnP）是晚期胰腺导管腺癌（PDAC）的标准一线治疗方案。然而,目前,缺乏预测性生物标志物来帮助治疗选择.我们旨在探讨III类β-微管蛋白（TUBB3）和人平衡核苷转运蛋白1（hENT1）表达的预后和预测价值。先前已显示与晚期PDAC中紫杉烷和吉西他滨耐药有关。
方法：我们对在我们机构接受GnP和/或FOLFIRINOX治疗的106例晚期PDAC患者进行了回顾性分析。对肿瘤标本进行TUBB3和hENT1免疫组织化学染色,随后基于表达的强度和百分比进行评估。
结果：在接受GnP方案的患者中，与中等(TUBB3high/hENT1high或TUBB3low/hENT1low)和低分(TUBB3high/hENT1low)相比,高综合评分(TUBB3low/hENT1low)与较高的DCR和较长的PFS相关.在多变量分析中，高综合评分是较高DCR(OR:11.96;95%CI:2.61-54.82;p=0.001)和较长PFS(HR:0.33;95CI:0.18-0.60;p<0.001)的独立预测因子.然而,在接受FOLFIRINOX方案的患者中,基于TUBB3和hENT1表达的缓解率或PFS无差异.
结论：我们的研究结果表明肿瘤TUBB3和hENT1的表达可以预测GnP方案的疗效，在接受GnP治疗的患者中，低TUBB3和高hENT1表达（TUBB3low/hENT1high）与较高的DCR和较长的PFS相关。联合评估TUBB3和hENT1可以识别最有可能(以及最少)受益于GnP化疗的患者。
方法：我们对在我们机构接受GnP和/或FOLFIRINOX治疗的106例晚期PDAC患者进行了回顾性分析。对肿瘤标本进行TUBB3和hENT1免疫组织化学染色,随后基于表达的强度和百分比进行评估。
结果：在接受GnP方案的患者中，与中等(TUBB3high/hENT1high或TUBB3low/hENT1low)和低分(TUBB3high/hENT1low)相比,高综合评分(TUBB3low/hENT1low)与较高的DCR和较长的PFS相关.在多变量分析中，高综合评分是较高DCR(OR:11.96;95%CI:2.61-54.82;p=0.001)和较长PFS(HR:0.33;95CI:0.18-0.60;p<0.001)的独立预测因子.然而,在接受FOLFIRINOX方案的患者中,基于TUBB3和hENT1表达的缓解率或PFS无差异.
结论：我们的研究结果表明肿瘤TUBB3和hENT1的表达可以预测GnP方案的疗效，在接受GnP治疗的患者中，低TUBB3和高hENT1表达（TUBB3low/hENT1high）与较高的DCR和较长的PFS相关。联合评估TUBB3和hENT1可以识别最有可能(以及最少)受益于GnP化疗的患者。
