Plectin-1 as a novel biomarker for pancreatic cancer

Dirk Bausch, Stephanie Thomas, Mari Mino-Kenudson, Carlos Fernández-del Castillo, Todd W. Bauer, Mark Williams, Andrew L. Warshaw, Sarah P Thayer, Kimberly A. Kelly

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Abstract

Purpose: We are in great need of specific biomarkers to detect pancreatic ductal adenocarcinoma (PDAC) at an early stage, ideally before invasion. Plectin-1 (Plec1) was recently identified as one such biomarker. However, its suitability as a specific biomarker for human pancreatic cancer, and its usability as an imaging target, remain to be assessed. Experimental Design: Specimens of human PDAC, chronic pancreatitis, and normal pancreata were evaluated by immunohistochemistry and Western blot analysis. To validate Plec1 as an imaging target, Plec1-targeting peptides (tPTP) were used as a contrast agent for single photon emission computed tomography in an orthotopic and liver metastasis murine model of PDAC. Results: Plec1 expression was noted to be positive in all PDACs but negative in benign tissues. Plec1 expression increases during pancreatic carcinogenesis. It was found to be misexpressed in only 0% to 3.85% of early PDAC precursor lesions (PanIN I/II) but in 60% of PanIN III lesions. Plec1 expression was further noted to be retained in all metastatic foci assayed and clearly highlighted these metastatic deposits in lymph nodes, liver, and peritoneum. In vivo imaging using tPTP specifically highlighted the primary and metastatic tumors. Biodistribution studies performed after imaging show that the primary pancreatic tumors and liver metastases retained 1.9- to 2.9-fold of tPTP over normal pancreas and 1.7-fold over normal liver. Conclusions: Plec1 is the first biomarker to identify primary and metastatic PDAC by imaging and may also detect preinvasive PanIN III lesions. Strategies designed to image Plec1 could therefore improve detection and staging.

Original languageEnglish (US)
Pages (from-to)302-309
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number2
DOIs
StatePublished - Jan 15 2011

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Plectin
Pancreatic Neoplasms
Biomarkers
Adenocarcinoma
Liver
Peptides
Pancreas
Neoplasm Metastasis
Peritoneum
Chronic Pancreatitis
Single-Photon Emission-Computed Tomography
Contrast Media
Neoplasms
Carcinogenesis
Research Design
Lymph Nodes
Western Blotting
Immunohistochemistry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Bausch, D., Thomas, S., Mino-Kenudson, M., Fernández-del Castillo, C., Bauer, T. W., Williams, M., ... Kelly, K. A. (2011). Plectin-1 as a novel biomarker for pancreatic cancer. Clinical Cancer Research, 17(2), 302-309. https://doi.org/10.1158/1078-0432.CCR-10-0999

Plectin-1 as a novel biomarker for pancreatic cancer. / Bausch, Dirk; Thomas, Stephanie; Mino-Kenudson, Mari; Fernández-del Castillo, Carlos; Bauer, Todd W.; Williams, Mark; Warshaw, Andrew L.; Thayer, Sarah P; Kelly, Kimberly A.

In: Clinical Cancer Research, Vol. 17, No. 2, 15.01.2011, p. 302-309.

Research output: Contribution to journalArticle

Bausch, D, Thomas, S, Mino-Kenudson, M, Fernández-del Castillo, C, Bauer, TW, Williams, M, Warshaw, AL, Thayer, SP & Kelly, KA 2011, 'Plectin-1 as a novel biomarker for pancreatic cancer', Clinical Cancer Research, vol. 17, no. 2, pp. 302-309. https://doi.org/10.1158/1078-0432.CCR-10-0999
Bausch D, Thomas S, Mino-Kenudson M, Fernández-del Castillo C, Bauer TW, Williams M et al. Plectin-1 as a novel biomarker for pancreatic cancer. Clinical Cancer Research. 2011 Jan 15;17(2):302-309. https://doi.org/10.1158/1078-0432.CCR-10-0999
Bausch, Dirk ; Thomas, Stephanie ; Mino-Kenudson, Mari ; Fernández-del Castillo, Carlos ; Bauer, Todd W. ; Williams, Mark ; Warshaw, Andrew L. ; Thayer, Sarah P ; Kelly, Kimberly A. / Plectin-1 as a novel biomarker for pancreatic cancer. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 2. pp. 302-309.
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abstract = "Purpose: We are in great need of specific biomarkers to detect pancreatic ductal adenocarcinoma (PDAC) at an early stage, ideally before invasion. Plectin-1 (Plec1) was recently identified as one such biomarker. However, its suitability as a specific biomarker for human pancreatic cancer, and its usability as an imaging target, remain to be assessed. Experimental Design: Specimens of human PDAC, chronic pancreatitis, and normal pancreata were evaluated by immunohistochemistry and Western blot analysis. To validate Plec1 as an imaging target, Plec1-targeting peptides (tPTP) were used as a contrast agent for single photon emission computed tomography in an orthotopic and liver metastasis murine model of PDAC. Results: Plec1 expression was noted to be positive in all PDACs but negative in benign tissues. Plec1 expression increases during pancreatic carcinogenesis. It was found to be misexpressed in only 0{\%} to 3.85{\%} of early PDAC precursor lesions (PanIN I/II) but in 60{\%} of PanIN III lesions. Plec1 expression was further noted to be retained in all metastatic foci assayed and clearly highlighted these metastatic deposits in lymph nodes, liver, and peritoneum. In vivo imaging using tPTP specifically highlighted the primary and metastatic tumors. Biodistribution studies performed after imaging show that the primary pancreatic tumors and liver metastases retained 1.9- to 2.9-fold of tPTP over normal pancreas and 1.7-fold over normal liver. Conclusions: Plec1 is the first biomarker to identify primary and metastatic PDAC by imaging and may also detect preinvasive PanIN III lesions. Strategies designed to image Plec1 could therefore improve detection and staging.",
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