Longitudinal Study of Circulating Biomarkers in Patients with Resectable Pancreatic Ductal Adenocarcinoma.
Longitudinal Study of Circulating Biomarkers in Patients with Resectable Pancreatic Ductal Adenocarcinoma.
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可切除胰导管腺癌患者循环生物标志物的纵向研究。
DOI：
10.3390/bios12040206
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发表时间：
2022-03-30
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影响因子：
--
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与不可切除的胰腺导管腺癌（PDAC）患者相比，可切除的PDAC患者生存率有所提高，但由于隐匿性转移性疾病和治疗耐药性，生存率仍然较低。基于循环肿瘤细胞（CTCs）和无细胞DNA（cfDNA）的液体活检已被证明可预测多种癌症的复发和治疗耐药性，但它们在可切除的PDAC中的效用尚未完全得到证实。我们使用微流控设备和液滴数字PCR（ddPCR）在癌症治疗期间同时追踪了三种循环生物标志物，包括CTCs、cfDNA和循环肿瘤DNA（ctDNA）。该微流控设备基于过滤和免疫亲和机制的结合。我们对7例接受新辅助治疗后进行手术的可切除PDAC患者队列测量了CTCs、cfDNA和ctDNA，在4个月的时间内对每位患者进行了多达10个时间点的随访。在治疗过程中的某个时间点，所有患者（100%）都可检测到CTCs，但在治疗开始前，6例患者中只有3例（50%）可检测到。在整个治疗过程中，cfDNA浓度中位数与阴性对照相当。ddPCR能够在7例患者中的6例（86%）中发现KRAS突变；然而，在治疗前，这些突变仅在7例患者中的2例（29%）中存在。总体而言，大多数循环生物标志物（CTCs为81%，cfDNA/ctDNA为91%）是在新辅助治疗开始后但在手术前检测到的。这项研究表明，对可切除的PDAC患者而言，在整个治疗过程中对循环生物标志物进行纵向研究比那些单一时间点的检测能提供更有用的信息。
While patients with resectable pancreatic ductal adenocarcinoma (PDAC) show improved survival compared to their non-resectable counterparts, survival remains low owing to occult metastatic disease and treatment resistance. Liquid biopsy based on circulating tumor cells (CTCs) and cell-free DNA (cfDNA) has been shown to predict recurrence and treatment resistance in various types of cancers, but their utility has not been fully demonstrated in resectable PDAC. We have simultaneously tracked three circulating biomarkers, including CTCs, cfDNA, and circulating tumor DNA (ctDNA), over a period of cancer treatment using a microfluidic device and droplet digital PCR (ddPCR). The microfluidic device is based on the combination of filtration and immunoaffinity mechanisms. We have measured CTCs, cfDNA, and ctDNA in a cohort of seven resectable PDAC patients undergoing neoadjuvant therapy followed by surgery, and each patient was followed up to 10 time points over a period of 4 months. CTCs were detectable in all patients (100%) at some point during treatment but were detectable in only three out of six patients (50%) prior to the start of treatment. Median cfDNA concentrations remained comparable to negative controls throughout treatment. ddPCR was able to find KRAS mutations in six of seven patients (86%); however, these mutations were present in only two of seven patients (29%) prior to treatment. Overall, the majority of circulating biomarkers (81% for CTCs and 91% for cfDNA/ctDNA) were detected after the start of neoadjuvant therapy but before surgery. This study suggests that a longitudinal study of circulating biomarkers throughout treatment provides more useful information than those single time-point tests for resectable PDAC patients.
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影响因子：
3.7
作者：
Luo J;Xiao L;Wu C;Zheng Y;Zhao N
通讯作者：
Zhao N
影响因子：
2.9
作者：
Deer EL;González-Hernández J;Coursen JD;Shea JE;Ngatia J;Scaife CL;Firpo MA;Mulvihill SJ
通讯作者：
Mulvihill SJ
影响因子：
16.6
作者：
Chen, Kangfu;Dopico, Pablo;Fan, Z. Hugh
通讯作者：
Fan, Z. Hugh
影响因子：
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作者：
Bissolati, Massimiliano;Sandri, Maria Teresa;Braga, Marco
通讯作者：
Braga, Marco
影响因子：
7.4
作者：
Hindson, Benjamin J.;Ness, Kevin D.;Masquelier, Donald A.;Belgrader, Phillip;Heredia, Nicholas J.;Makarewicz, Anthony J.;Bright, Isaac J.;Lucero, Michael Y.;Hiddessen, Amy L.;Legler, Tina C.;Kitano, Tyler K.;Hodel, Michael R.;Petersen, Jonathan F.;Wyatt, Paul W.;Steenblock, Erin R.;Shah, Pallavi H.;Bousse, Luc J.;Troup, Camille B.;Mellen, Jeffrey C.;Wittmann, Dean K.;Erndt, Nicholas G.;Cauley, Thomas H.;Koehler, Ryan T.;So, Austin P.;Dube, Simant;Rose, Klint A.;Montesclaros, Luz;Wang, Shenglong;Stumbo, David P.;Hodges, Shawn P.;Romine, Steven;Milanovich, Fred P.;White, Helen E.;Regan, John F.;Karlin-Neumann, George A.;Hindson, Christopher M.;Saxonov, Serge;Colston, Bill W.
通讯作者：
Colston, Bill W.