Badovinac David, Goričar Katja, Lavrin Teja, Zavrtanik Hana, Dolžan Vita, Lenassi Metka, Tomažič Aleš
Department of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia.
Department of Surgery, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Cancers (Basel). 2023 Jan 18;15(3):605. doi: 10.3390/cancers15030605.
Due to possible diagnostic misjudgment of tumor resectability, patients with pancreatic ductal adenocarcinoma (PDAC) might be exposed to non-radical resection or unnecessary laparotomy. With small extracellular vesicles (sEV) obtained by liquid biopsy, we aimed to evaluate their potential as biomarkers of tumor resectability, radicality of resection and overall survival (OS). Our prospective study included 83 PDAC patients undergoing surgery with curative intent followed-up longitudinally. sEV were isolated from plasma, and their concentration and size were determined. Fifty patients underwent PDAC resection, and thirty-three had no resection. Preoperatively, patients undergoing resection had higher sEV concentrations than those without resection ( = 0.023). Resection was predicted at the cutoff value of 1.88 × 10/mL for preoperative sEV concentration ( = 0.023) and the cutoff value of 194.8 nm for preoperative mean diameter ( = 0.057). Furthermore, patients with R0 resection demonstrated higher preoperative plasma sEV concentrations than patients with R1/R2 resection ( = 0.014). If sEV concentration was above 1.88 × 10/mL or if the mean diameter was below 194.8 nm, patients had significantly longer OS ( = 0.018 and = 0.030, respectively). Our proof-of-principle study identified preoperative sEV characteristics as putative biomarkers of feasibility and radicality of PDAC resection that also enable discrimination of patients with worse OS. Liquid biopsy with sEV could aid in PDAC patient stratification and treatment optimization in the future.
由于胰腺导管腺癌(PDAC)的肿瘤可切除性可能存在诊断误判,患者可能会接受非根治性切除或不必要的剖腹手术。通过液体活检获得的小细胞外囊泡(sEV),我们旨在评估其作为肿瘤可切除性、切除根治性和总生存期(OS)生物标志物的潜力。我们的前瞻性研究纳入了83例接受根治性手术的PDAC患者,并进行纵向随访。从血浆中分离出sEV,并测定其浓度和大小。50例患者接受了PDAC切除,33例未进行切除。术前,接受切除的患者sEV浓度高于未切除的患者(P = 0.023)。术前sEV浓度的截断值为1.88×10⁹/mL时预测可进行切除(P = 0.023),术前平均直径的截断值为194.8 nm时预测可进行切除(P = 0.057)。此外,R0切除的患者术前血浆sEV浓度高于R1/R2切除的患者(P = 0.014)。如果sEV浓度高于1.88×10⁹/mL或平均直径低于194.8 nm,患者的总生存期显著更长(分别为P = 0.018和P = 0.030)。我们的原理验证研究确定术前sEV特征可作为PDAC切除可行性和根治性的推定生物标志物,也能够区分总生存期较差的患者。未来,sEV液体活检可能有助于PDAC患者的分层和治疗优化。