Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer

Abstract

Background/Aims: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in extremely poor 5-year survival. Late diagnosis of PDAC is mainly due to lack of a reliable method of early detection. Carbohydrate antigen (CA) 19-9 is often used as a tumor biomarker in PDAC; however, the test lacks sensitivity and specificity. Therefore, new sensitive and minimally invasive diagnostic tools are required to detect pancreatic cancer. Methods: Here, we investigated circulating tumor DNA (ctDNA) which contained KRAS-mutated as a potential diagnostic tool for PDAC patients who underwent irreversible electroporation (IRE). We used droplet digital polymerase chain reaction (ddPCR) to detect the expression of KRAS-mutated genes in plasma samples of 65 PDAC patients who underwent IRE. Results: In these 65 cases, ctDNA was detected in 20 (29.2%) samples. The median overall survival (OS) was 11.4 months with ctDNA+ patients and 14.3 months for ctDNA- patients. ctDNA+ patients had a obviously poorer prognosis associated to overall survival (P < 0.001). Conclusion: Our results suggested that the existence of ctDNA was a predictor of survival for PDAC patients. Therefore, ctDNA may be a new sensitive biomarker for monitoring treatment outcome in PDAC.

Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma

“…In relation to technical aspects, previous studies have interrogated regions ranging from a single locus of KRAS to comprehensive cancer panels covering >20 genes. 9,30,35,37 PDAC shows a very homogeneous mutational landscape with KRAS mutations in approximately 90% of cases, barring the need for extensive coverage and patient-tailored primers. 18,38,39 This implies that ddPCR, which has a lower limit of detection than NGS, would be eminently suited to PDAC.…”

MicroRNA‐124: An emerging therapeutic target in cancer

“…Therefore, in‐depth studies of the pathogenesis of CRC play an important role in human health. Liu et al demonstrated that underexpressed miR‐124 could regulate inhibitor of apoptosis‐stimulating protein of p53 (iASPP) in CRC patients and was related to the proliferation of CRC cells via influencing the iASPP/NF‐kB pathway . In addition, miR‐124 inhibited the target gene polypyrimidine tract‐binding protein 1 (PTB1) in the DLD‐1 CRC cell line.…”

“…Pancreatic cancer is always diagnosed in late stage due to the lack of clinical manifestations. 60 So far, there are not many effective targeted therapies to reduce its mortality. 61 Emphasis has been placed on deeply investigating miR-124 to reveal its role as a tumor suppressor or protooncogene.…”

“…Pancreatic cancer is always diagnosed in late stage due to the lack of clinical manifestations . So far, there are not many effective targeted therapies to reduce its mortality .…”

Impact of circulating tumor DNA in hepatocellular and pancreatic carcinomas

“…Therefore, KRAS mutant ctDNA represents a promising biomarker and therapeutic target of PC. Using ddPCR and targeted NGS, different KRAS mutations were detected in up to 80% of PC serum and plasma samples and were associated with decreased survival (Adamo et al 2017;Ako et al 2017;Chen et al 2010;Cohen et al 2017;Dabritz et al 2009;Del Re et al 2017;Dianxu et al 2002;Earl et al 2015;Hadano et al 2016;Jiao et al 2007;Kim et al 2018;Kinugasa et al 2015;Kruger et al 2018;Lin et al 2018;Maire et al 2002;Marchese et al 2006;Nakano et al 2018;Park et al 2018;Patel et al 2019;Perets et al 2018;Pratt et al 2019;Riviere et al 2018;Sausen et al 2015;Semrad et al 2015;Sugimori et al 2020;Takai et al 2015;Tjensvoll et al 2016;Uemura et al 2004;Van Laethem et al 2017;Watanabe et al 2019;Wu et al 2014). Chen et al published a KRAS mutant ctDNA detection rate of 93.7% which correlates with time to progression and overall survival of 189 patients with unresectable PC (Chen et al 2017).…”