Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated.
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Knockdown of LGALS1 in vitro reduced cell migration and invasion capabilities in pancreatic cancer associated cells.
“knockdown of LGALS1 in vitro reduced cell migration and invasion capabilities in pancreatic cancer associated cells34.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as [34]
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Proteomics signatures of human breast cancer: A systematic review
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- Authors
- Chen, R., Dawson, D. W., Pan, S., Ottenhof, N. A., de Wilde, R. F., Wolfgang, C. L., May, D. H., Crispin, D. A., Lai, L. A., Lay, A. R., Waghray, M., Wang, S., McIntosh, M. W., Simeone, D. M., Maitra, A., & Brentnall, T. A.
- Affiliations
- University of Washington (US)
- University of California, Los Angeles (US)
- Johns Hopkins University (US)
- Fred Hutch Cancer Center (US)
- University of Michigan (US)
- Soochow University (CN)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Chen, Ru
- ORCID
- Venue
- Laboratory Investigation
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 95
- Issue
- 1
- Pages
- 43-55
- ISSN
- 0023-6837 (ISSN-L)
- PMC
- PMC4281293
- OpenAlex
- W2057594180
- Cited by
- 59
- References
- 45
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 10 · 2016: 3 · 2015: 3
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Johns Hopkins University
- National Institutes of Health
- National Cancer Institute (R21CA149772, R01CA180949, K07CA116296, R21CA161575, P01CA163200, K25CA137222, P30CA016042)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK041301)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- pancreatic ductal adenocarcinoma, tumor proteome, prognostic factors, ribosomal protein S8, PRELP, galectin-1, cancer-associated fibroblasts, c-Myc, IGF-1 receptor, p53, VEGF-A, apolipoprotein E, TGF-β1, cell migration and invasion, therapeutic target
- MeSH terms
- Adenocarcinoma, Female, Humans, Male, Middle Aged, Neoplasm Proteins, Pancreatic Neoplasms, Survival Analysis, Carcinoma, Pancreatic Ductal, Proteomics, Cell Line, Tumor
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