高表达 kruppel 样因子 10 或 Smad4 预测可切除胰腺腺癌辅助放化疗的临床获益：来自一项随机 III 期试验。

High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma: From a randomized phase III trial.

机构信息

Department of Pathology, National Cheng Kung University, Tainan, Taiwan.

Department of Surgery, National Cheng Kung University, Tainan, Taiwan.

出版信息

Radiother Oncol. 2021 May;158:146-154. doi: 10.1016/j.radonc.2021.02.037. Epub 2021 Mar 3.

DOI:10.1016/j.radonc.2021.02.037

PMID:33667587

Abstract

PURPOSE

Our previous studies have demonstrated that Krüppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC.

METHODS AND MATERIALS

Tissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software.

RESULTS

In total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p = 0.013, 0.045, and 0.047, respectively). Multivariable analysis showed that the expression level of postoperative serum CA19-9 and tumor tissue Klf10 expression level were significant predictors for OS (p = 0.038, and 0.028, respectively). Patients with high Klf10 or Smad4 (n = 55), had a significantly better local recurrence-free survival (∞ vs 19.8 months; p = 0.026) and a longer OS (33.0 vs 23.0 months; p = 0.12) if they received additional adjuvant CRT than gemcitabine only. The results were similar after adjusted by postoperative level of CA19-9.

CONCLUSION

Patients with curatively resected PDAC and a high expression of either Klf10 or Smad4 have high chances of benefiting from adjuvant CRT. Combining Klf10 and Smad4 to predict the benefits of adjuvant CRT in resected PDAC deserves further validation.

摘要

目的

我们之前的研究表明，Krüppel 样因子 10（Klf10）调节肿瘤放射抵抗，并有助于预测胰腺腺癌（PDAC）的临床结局。本研究旨在评估 Klf10、Smad4 和 Runx3 的表达水平是否有助于预测可切除 PDAC 患者辅助放化疗（CRT）的获益。

方法和材料

从 111 名接受根治性手术治疗的 PDAC 患者中收集组织标本，这些患者被纳入一项比较吉西他滨辅助治疗加或不加 CRT 的随机试验。通过基于染色程度和强度的分级系统，由对患者结局不知情的病理学家对生物标志物的免疫组织化学表达进行定量。使用 SAS 统计软件分析生物标志物的预测价值。

结果

共有 56 例和 55 例患者分别接受吉西他滨单药辅助治疗和加用 CRT。Klf10、Smad4 和术后 CA19-9 的表达水平与总生存（OS）显著相关（p=0.013、0.045 和 0.047）。多变量分析显示，术后血清 CA19-9 水平和肿瘤组织 Klf10 表达水平是 OS 的显著预测因素（p=0.038 和 0.028）。Klf10 或 Smad4 高表达的患者（n=55）如果接受辅助 CRT 加吉西他滨治疗，其局部无复发生存率（∞与 19.8 个月；p=0.026）和 OS（33.0 与 23.0 个月；p=0.12）显著改善。在调整术后 CA19-9 水平后，结果相似。