Circulating Tumor Cells and Transforming Growth Factor Beta in Resected Pancreatic Adenocarcinoma

Diego Vicente; Andrew J. Lee; Carolyn S. Hall; Anthony Lucci; Jeffrey E. Lee; Michael P. Kim; Matthew HG Katz; Mark W. Hurd; Anirban Maitra; Andrew D. Rhim, MD; Ching Wei D. Tzeng

doi:10.1016/j.jss.2019.04.090

Circulating Tumor Cells and Transforming Growth Factor Beta in Resected Pancreatic Adenocarcinoma

Diego Vicente^*, Andrew J. Lee, Carolyn S. Hall, Anthony Lucci, Jeffrey E. Lee, Michael P. Kim, Matthew HG Katz, Mark W. Hurd, Anirban Maitra, Andrew D. Rhim, MD, Ching Wei D. Tzeng

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Background: Portal vein (PV) circulating tumor cells (CTCs) and elevated peripheral blood (PB) levels of biomarkers have been associated with poor outcomes in pancreatic ductal adenocarcinoma (PDAC). Although transforming growth factor-beta (TGFβ) is associated with CTCs in breast cancer, there are limited data evaluating a comprehensive biomarker panel and CTCs in PDAC patients. The authors hypothesized that tumor progression biomarkers would be associated with PV CTCs. Methods: PDAC patients at one institution were enrolled January to August 2018 and underwent preincision PB draws (T0) and on postoperative day 1 (T3), plus intraoperative PV draws before tumor manipulation (T1) and after resection (T2). CTCs were detected using CellSearch. Plasma biomarker levels (pg/mL) were measured with a multiplex bead assay. Patients were divided into two groups: high (≥3 CTCs/7.5 mL blood) versus low (<3). Clinicopathologic variables and biomarkers were compared in the two groups. Results: Fourteen had complete blood draws with PDAC resection, with five demonstrating high CTCs. Fewer patients in the high-CTC group received preoperative radiation (78 versus 20%), whereas more of the high-CTC had pT3 tumors (80 versus 11%) (all P < 0.037). High-CTC patients demonstrated higher TGFβ-2 levels (T0 [906 versus 586], T1 [1337 versus 627], T2 [1149 versus 445]), as well as higher TGFβ-3 (T0 [320 versus 173], T2 [605 versus 120]) (all P < 0.021). Conclusions: PDAC patients with high CTCs demonstrated a distinct biomarker profile with elevated PB and PV levels of immunosuppressive cytokines (TGFβ-2 and TGFβ-3). These exploratory results prompt further study into interrupting TGFβ signaling.

Original language	English
Pages (from-to)	90-99
Number of pages	10
Journal	Journal of Surgical Research
Volume	243
DOIs	https://doi.org/10.1016/j.jss.2019.04.090
State	Published - Nov 2019
Externally published	Yes

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@article{28e5723df44a4987876afdb4cad1f63e,

title = "Circulating Tumor Cells and Transforming Growth Factor Beta in Resected Pancreatic Adenocarcinoma",

abstract = "Background: Portal vein (PV) circulating tumor cells (CTCs) and elevated peripheral blood (PB) levels of biomarkers have been associated with poor outcomes in pancreatic ductal adenocarcinoma (PDAC). Although transforming growth factor-beta (TGFβ) is associated with CTCs in breast cancer, there are limited data evaluating a comprehensive biomarker panel and CTCs in PDAC patients. The authors hypothesized that tumor progression biomarkers would be associated with PV CTCs. Methods: PDAC patients at one institution were enrolled January to August 2018 and underwent preincision PB draws (T0) and on postoperative day 1 (T3), plus intraoperative PV draws before tumor manipulation (T1) and after resection (T2). CTCs were detected using CellSearch. Plasma biomarker levels (pg/mL) were measured with a multiplex bead assay. Patients were divided into two groups: high (≥3 CTCs/7.5 mL blood) versus low (<3). Clinicopathologic variables and biomarkers were compared in the two groups. Results: Fourteen had complete blood draws with PDAC resection, with five demonstrating high CTCs. Fewer patients in the high-CTC group received preoperative radiation (78 versus 20%), whereas more of the high-CTC had pT3 tumors (80 versus 11%) (all P < 0.037). High-CTC patients demonstrated higher TGFβ-2 levels (T0 [906 versus 586], T1 [1337 versus 627], T2 [1149 versus 445]), as well as higher TGFβ-3 (T0 [320 versus 173], T2 [605 versus 120]) (all P < 0.021). Conclusions: PDAC patients with high CTCs demonstrated a distinct biomarker profile with elevated PB and PV levels of immunosuppressive cytokines (TGFβ-2 and TGFβ-3). These exploratory results prompt further study into interrupting TGFβ signaling.",

author = "Diego Vicente and Lee, {Andrew J.} and Hall, {Carolyn S.} and Anthony Lucci and Lee, {Jeffrey E.} and Kim, {Michael P.} and Katz, {Matthew HG} and Hurd, {Mark W.} and Anirban Maitra and {Rhim, MD}, {Andrew D.} and Tzeng, {Ching Wei D.}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = nov,

doi = "10.1016/j.jss.2019.04.090",

language = "English",

volume = "243",

pages = "90--99",

journal = "Journal of Surgical Research",

issn = "0022-4804",

publisher = "Elsevier",

}

TY - JOUR

T1 - Circulating Tumor Cells and Transforming Growth Factor Beta in Resected Pancreatic Adenocarcinoma

AU - Vicente, Diego

AU - Lee, Andrew J.

AU - Hall, Carolyn S.

AU - Lucci, Anthony

AU - Lee, Jeffrey E.

AU - Kim, Michael P.

AU - Katz, Matthew HG

AU - Hurd, Mark W.

AU - Maitra, Anirban

AU - Rhim, MD, Andrew D.

AU - Tzeng, Ching Wei D.

PY - 2019/11

Y1 - 2019/11

N2 - Background: Portal vein (PV) circulating tumor cells (CTCs) and elevated peripheral blood (PB) levels of biomarkers have been associated with poor outcomes in pancreatic ductal adenocarcinoma (PDAC). Although transforming growth factor-beta (TGFβ) is associated with CTCs in breast cancer, there are limited data evaluating a comprehensive biomarker panel and CTCs in PDAC patients. The authors hypothesized that tumor progression biomarkers would be associated with PV CTCs. Methods: PDAC patients at one institution were enrolled January to August 2018 and underwent preincision PB draws (T0) and on postoperative day 1 (T3), plus intraoperative PV draws before tumor manipulation (T1) and after resection (T2). CTCs were detected using CellSearch. Plasma biomarker levels (pg/mL) were measured with a multiplex bead assay. Patients were divided into two groups: high (≥3 CTCs/7.5 mL blood) versus low (<3). Clinicopathologic variables and biomarkers were compared in the two groups. Results: Fourteen had complete blood draws with PDAC resection, with five demonstrating high CTCs. Fewer patients in the high-CTC group received preoperative radiation (78 versus 20%), whereas more of the high-CTC had pT3 tumors (80 versus 11%) (all P < 0.037). High-CTC patients demonstrated higher TGFβ-2 levels (T0 [906 versus 586], T1 [1337 versus 627], T2 [1149 versus 445]), as well as higher TGFβ-3 (T0 [320 versus 173], T2 [605 versus 120]) (all P < 0.021). Conclusions: PDAC patients with high CTCs demonstrated a distinct biomarker profile with elevated PB and PV levels of immunosuppressive cytokines (TGFβ-2 and TGFβ-3). These exploratory results prompt further study into interrupting TGFβ signaling.

AB - Background: Portal vein (PV) circulating tumor cells (CTCs) and elevated peripheral blood (PB) levels of biomarkers have been associated with poor outcomes in pancreatic ductal adenocarcinoma (PDAC). Although transforming growth factor-beta (TGFβ) is associated with CTCs in breast cancer, there are limited data evaluating a comprehensive biomarker panel and CTCs in PDAC patients. The authors hypothesized that tumor progression biomarkers would be associated with PV CTCs. Methods: PDAC patients at one institution were enrolled January to August 2018 and underwent preincision PB draws (T0) and on postoperative day 1 (T3), plus intraoperative PV draws before tumor manipulation (T1) and after resection (T2). CTCs were detected using CellSearch. Plasma biomarker levels (pg/mL) were measured with a multiplex bead assay. Patients were divided into two groups: high (≥3 CTCs/7.5 mL blood) versus low (<3). Clinicopathologic variables and biomarkers were compared in the two groups. Results: Fourteen had complete blood draws with PDAC resection, with five demonstrating high CTCs. Fewer patients in the high-CTC group received preoperative radiation (78 versus 20%), whereas more of the high-CTC had pT3 tumors (80 versus 11%) (all P < 0.037). High-CTC patients demonstrated higher TGFβ-2 levels (T0 [906 versus 586], T1 [1337 versus 627], T2 [1149 versus 445]), as well as higher TGFβ-3 (T0 [320 versus 173], T2 [605 versus 120]) (all P < 0.021). Conclusions: PDAC patients with high CTCs demonstrated a distinct biomarker profile with elevated PB and PV levels of immunosuppressive cytokines (TGFβ-2 and TGFβ-3). These exploratory results prompt further study into interrupting TGFβ signaling.

UR - http://www.scopus.com/inward/record.url?scp=85066402656&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2019.04.090

DO - 10.1016/j.jss.2019.04.090

M3 - Article

C2 - 31170555

AN - SCOPUS:85066402656

SN - 0022-4804

VL - 243

SP - 90

EP - 99

JO - Journal of Surgical Research

JF - Journal of Surgical Research

ER -

Circulating Tumor Cells and Transforming Growth Factor Beta in Resected Pancreatic Adenocarcinoma

Abstract

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