The prognosis of pancreatic adenocarcinoma (PDAC) remains poor, with a 5-year survival rate of 12%. Although radiotherapy is effective for the locoregional control of PDAC, it does not have survival benefits compared with systemic chemotherapy. Most patients with localized PDAC develop distant metastasis shortly after diagnosis. Upfront chemotherapy has been suggested so that patients with localized PDAC with early distant metastasis do not have to undergo radical local therapy. Several potential tissue markers have been identified for selecting patients who may benefit from local radiotherapy, thereby prolonging their survival. This review summarizes these biomarkers includingSMAD4, which is significantly associated with PDAC failure patterns and survival. In particular, Krüppel-like factor 10 (KLF10) is an early response transcription factor of transforming growth factor (TGF)-β. UnlikeTGF-βin advanced cancers,KLF10loss in two-thirds of patients with PDAC was associated with rapid distant metastasis and radioresistance; thus,KLF10can serve as a predictive and therapeutic marker for PDAC. For patients with resectable PDAC, a combination ofKLF10andSMAD4expression in tumor tissues may help select those who may benefit the most from additional radiotherapy. Future trials should consider upfront systemic therapy or include molecular biomarker-enriched patients without early distant metastasis.
胰腺导管腺癌（PDAC）的预后仍然较差，5年生存率仅为12%。尽管放疗对PDAC的局部区域控制有效，但与全身化疗相比，并未显示出生存获益。大多数局限性PDAC患者在确诊后不久即发生远处转移。因此建议对局限性PDAC患者先行化疗，以避免早期发生远处转移的患者接受根治性局部治疗。目前已发现多种潜在的组织标志物，可用于筛选可能从局部放疗中获益从而延长生存期的患者。本综述总结了这些生物标志物，包括与PDAC失败模式和生存显著相关的SMAD4。特别是Krüppel样因子10（KLF10），它是转化生长因子（TGF）-β的早期反应转录因子。与晚期癌症中的TGF-β不同，在三分之二的PDAC患者中，KLF10的缺失与快速远处转移和放射抵抗相关；因此，KLF10可作为PDAC的预测和治疗标志物。对于可切除的PDAC患者，结合肿瘤组织中KLF10和SMAD4的表达情况，可能有助于筛选出最能从辅助放疗中获益的患者。未来的临床试验应考虑先行全身治疗，或纳入分子生物标志物富集且无早期远处转移的患者。
肿瘤(癌症)患者之家