From the Departments of Hospital Pathology.
Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Pancreas. 2024 Sep 1;53(8):e681-e688. doi: 10.1097/MPA.0000000000002356. Epub 2024 Mar 27.
Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well.
We assessed the prognostic significance of PARP-1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray.
PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers ( P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses ( P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers.
PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs.
壶腹周围癌（PAC）侵袭性强，目前尚无有效的辅助治疗或预后标志物。最近，聚 ADP-核糖聚合酶-1（PARP-1）已成为实体瘤的一个治疗靶点，其与上皮间质转化（EMT）的关系已被观察到。然而，PARP-1 与 PAC 中的 EMT 之间的关系尚未得到充分探索。
我们评估了 190 例 PAC 患者中 PARP-1 的预后意义，并将其与 EMT 标志物（包括 FGF8、FGFR4、MMP2、MMP3、Snail 和 ZEB1）进行了相关性分析。使用组织微阵列进行了 PARP-1 和 EMT 标志物的免疫组织化学检测。
PARP-1 和 FGF8 的表达与更好的生存相关，与其他实体瘤不同（P=0.006 和 P=0.003），而 MMP3 和 ZEB1 的表达在多变量和生存分析中与不良预后相关（P=0.009 和 P<0.001）。此外，PARP-1 与 Snail 呈负相关，但与其他 EMT 标志物无关，这表明在 PAC 中，PARP-1 与 EMT 之间存在独立的机制。PARP-1 和 FGF8 是 PAC 中不同于其他实体瘤的独立良好生存标志物。
PARP-1 和 FGF8 在 PAC 中与 EMT 途径无关，而必须从类似的癌症保护作用的角度来理解。需要进一步研究 PAC 中与 EMT 相关的免疫标志物。
