Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma

Ru Chen, Sheng Pan, Niki A. Ottenhof, Roeland F. De Wilde, Christopher Wolfgang, Zhaoli Lane, Jane Post, Mary P. Bronner, Jürgen K. Willmann, Anirban Maitra, Teresa A. Brentnall

Research output: Contribution to journalArticle

Abstract

The overall 5-year survival rate for pancreatic ductal adenocarcinoma (i.e., PDAC) is a dismal 5%, although patients that have undergone surgical resection have a somewhat better survival rate of up to 20%. Very long-term survivors of PDAC (defined as patients with ≥ 10 year survival following apparently curative resection), on the other hand, are considerably less frequent. The molecular characteristics of very long-term survivors (VLTS) are poorly understood, but might provide novel insights into prognostication for this disease. In this study, a panel of five VLTS and stage-matched short-term survivors (STS, defined as disease-specific mortality within 14 months of resection) were identified, and quantitative proteomics was applied to comparatively profile tumor tissues from both cohorts. Differentially expressed proteins were identified in cancers from VLTS vs. STS patients. Specifically, the expression of galectin-1 was 2-fold lower in VLTS compared with STS tumors. Validation studies were performed by immunohistochemistry (IHC) in two additional cohorts of resected PDAC, including: (1) an independent cohort of VLTS and (2) a panel of sporadic PDAC with a considerable range of overall survival following surgery. Immunolabeling analysis confirmed that significantly lower expression of stromal galectin-1 was associated with VLTS (p = 0.02) and also correlated with longer survival in sporadic, surgically-treated PDAC cases (hazard ratio = 4.9, p = 0.002). The results from this study provide new insights to better understand the role of galectin-1 in PDAC survival, and might be useful for rendering prognostic information, and developing more effective therapeutic strategies aimed at improving survival.

Original languageEnglish (US)
Pages (from-to)899-907
Number of pages9
JournalCancer Biology and Therapy
Volume13
Issue number10
DOIs
StatePublished - Aug 2012

Fingerprint

Galectin 1
Survivors
Adenocarcinoma
Survival
Survival Rate
Neoplasms
Validation Studies
Proteomics
Immunohistochemistry
Mortality

Keywords

  • Galectin-1/galectin 1
  • Long-term
  • Pancreatic ductal adenocarcinoma/PDAC
  • Prognosis
  • Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma. / Chen, Ru; Pan, Sheng; Ottenhof, Niki A.; De Wilde, Roeland F.; Wolfgang, Christopher; Lane, Zhaoli; Post, Jane; Bronner, Mary P.; Willmann, Jürgen K.; Maitra, Anirban; Brentnall, Teresa A.

In: Cancer Biology and Therapy, Vol. 13, No. 10, 08.2012, p. 899-907.

Research output: Contribution to journalArticle

Chen, R, Pan, S, Ottenhof, NA, De Wilde, RF, Wolfgang, C, Lane, Z, Post, J, Bronner, MP, Willmann, JK, Maitra, A & Brentnall, TA 2012, 'Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma', Cancer Biology and Therapy, vol. 13, no. 10, pp. 899-907. https://doi.org/10.4161/cbt.20842
Chen, Ru ; Pan, Sheng ; Ottenhof, Niki A. ; De Wilde, Roeland F. ; Wolfgang, Christopher ; Lane, Zhaoli ; Post, Jane ; Bronner, Mary P. ; Willmann, Jürgen K. ; Maitra, Anirban ; Brentnall, Teresa A. / Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma. In: Cancer Biology and Therapy. 2012 ; Vol. 13, No. 10. pp. 899-907.
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AU - Pan, Sheng

AU - Ottenhof, Niki A.

AU - De Wilde, Roeland F.

AU - Wolfgang, Christopher

AU - Lane, Zhaoli

AU - Post, Jane

AU - Bronner, Mary P.

AU - Willmann, Jürgen K.

AU - Maitra, Anirban

AU - Brentnall, Teresa A.

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AB - The overall 5-year survival rate for pancreatic ductal adenocarcinoma (i.e., PDAC) is a dismal 5%, although patients that have undergone surgical resection have a somewhat better survival rate of up to 20%. Very long-term survivors of PDAC (defined as patients with ≥ 10 year survival following apparently curative resection), on the other hand, are considerably less frequent. The molecular characteristics of very long-term survivors (VLTS) are poorly understood, but might provide novel insights into prognostication for this disease. In this study, a panel of five VLTS and stage-matched short-term survivors (STS, defined as disease-specific mortality within 14 months of resection) were identified, and quantitative proteomics was applied to comparatively profile tumor tissues from both cohorts. Differentially expressed proteins were identified in cancers from VLTS vs. STS patients. Specifically, the expression of galectin-1 was 2-fold lower in VLTS compared with STS tumors. Validation studies were performed by immunohistochemistry (IHC) in two additional cohorts of resected PDAC, including: (1) an independent cohort of VLTS and (2) a panel of sporadic PDAC with a considerable range of overall survival following surgery. Immunolabeling analysis confirmed that significantly lower expression of stromal galectin-1 was associated with VLTS (p = 0.02) and also correlated with longer survival in sporadic, surgically-treated PDAC cases (hazard ratio = 4.9, p = 0.002). The results from this study provide new insights to better understand the role of galectin-1 in PDAC survival, and might be useful for rendering prognostic information, and developing more effective therapeutic strategies aimed at improving survival.

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