Shishido Stephanie N, Lin Emmeline, Nissen Nicholas, Courcoubetis George, Suresh Divya, Mason Jeremy, Osipov Arsen, Hendifar Andrew E, Lewis Michael, Gaddam Srinivas, Pandol Stephen, Kuhn Peter, Lo Simon K
Convergent Science Institute for Cancer, Michelson Center, University of Southern California, Los Angeles, CA, 90089, USA.
Pancreatic and Biliary Diseases Program, Cedars Sinai Medical Center, Los Angeles, CA, 90048, USA.
NPJ Precis Oncol. 2024 Feb 15;8(1):36. doi: 10.1038/s41698-024-00521-0.
Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of less than 10% due to its late diagnosis, rapid metastasis, and chemotherapeutic resistance. For a small proportion (10-20%) of early-stage patients however, surgical resection of the pancreatic tumor offers the best chance for survival but the effect of surgery on disease dissemination is unknown. The primary objective of this study was to characterize cellular and acellular blood-based analytes in portal and peripheral blood before pancreatic manipulation, during tumor dissection and immediately after surgical resection to determine the effects of the surgery. This study used the non-enriching third generation High-Definition Single Cell Assay (HDSCA3.0) workflow to investigate heterogeneous circulating rare cell population in the blood. Blood from both sites taken before surgical manipulation of the pancreas had significantly greater incidence of total rare cellular and acellular analytes than normal donor samples. Post-surgery portal and peripheral blood had significantly greater incidence of specific cellular and acellular subtypes compared to the matched pre- and during-surgery samples. Our results reveal that in patients with PDAC liquid biopsy analytes are increased in both the portal and peripheral blood; portal blood contains a higher frequency of analytes than in the peripheral blood; total analytes in the portal and peripheral blood samples were significantly associated with the tumor volume and pathological T stage; and the surgical procedure increased the blood levels of circulating cellular and acellular analytes, but not Epi.CTCs or Mes.CTCs. This study demonstrates liquid biopsy's utility in monitoring patients with PDAC with surgically resectable disease.
胰腺导管腺癌（PDAC）由于诊断较晚、转移迅速且具有化疗耐药性，其五年生存率低于10%。然而，对于一小部分（10 - 20%）早期患者而言，手术切除胰腺肿瘤提供了最佳的生存机会，但手术对疾病播散的影响尚不清楚。本研究的主要目的是在胰腺手术操作前、肿瘤切除过程中以及手术切除后立即对门静脉血和外周血中的细胞和无细胞血液分析物进行表征，以确定手术的效果。本研究采用非富集第三代高清单细胞分析（HDSCA3.0）工作流程来研究血液中异质循环稀有细胞群体。在胰腺手术操作前从两个部位采集的血液中，总的稀有细胞和无细胞分析物的发生率显著高于正常供体样本。与匹配的手术前和手术中样本相比，手术后门静脉血和外周血中特定细胞和无细胞亚型的发生率显著更高。我们的结果表明，在PDAC患者中，液体活检分析物在门静脉血和外周血中均增加；门静脉血中分析物的频率高于外周血；门静脉血和外周血样本中的总分析物与肿瘤体积和病理T分期显著相关；手术操作增加了循环细胞和无细胞分析物的血液水平，但未增加上皮循环肿瘤细胞（Epi.CTCs）或间充质循环肿瘤细胞（Mes.CTCs）的血液水平。本研究证明了液体活检在监测可手术切除的PDAC患者中的实用性。
