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Abstract 2817: An RNA aptamer is a potential biomarker for pancreatic cancer

Publication ,  Journal Article
Ray, P; Sullenger, BA; White, RR
Published in: Cancer Research
April 15, 2011

Introduction: The symptoms of pancreatic cancer are usually non-specific and late. Existing tumor markers (such as CA19-9 and CEA) are neither sensitive nor specific enough to serve as useful screening tests. Tools for earlier detection could increase the proportion of patients who are cured with surgical resection.Aptamers are oligonucleotide ligands that are identified from large libraries of RNA or DNA molecules using an iterative selection process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). Aptamers bind their specific targets with high affinity and specificity and can be used for the dual purpose of identifying novel biomarkers and detecting them in biological specimens.Methods: In order to select for aptamers against molecules that are selectively secreted by cancerous cells but not by normal cells, “positive/negative” SELEX was performed using the conditioned media (the “secretome”) of the MiaPaCa2 human pancreatic ductal adenocarcinoma cell line (positive selection) and the immortalized, non-cancerous human pancreatic ductal cell line HPDE (negative selection). Standard radioactive filter-based binding assays were used to measure binding.Results/Conclusion: We have successfully selected several nuclease resistant (2′-fluoro-modified) RNA aptamers that differentially bind the secretome of pancreatic cancer cells compared to non-cancerous cells. One of the aptamers (M9-5) binds pancreatic cancer patient sera with high affinity compared to control sera collected from healthy donors. So far, the aptamer has demonstrated specific binding in 20 of 22 patients with histologically-proven pancreatic cancer and none of 20 healthy donors. In addition, paired serum samples obtained from two patients pre- and post-chemoradiation therapy and one patient pre- and two months post-resection have demonstrated a decrease in M9-5 binding with decreased tumor burden. Notably, the serum CA19-9 and CEA levels in several of these patients were normal, indicating that our biomarker might be more sensitive than these existing serum biomarkers for pancreatic cancer. M9-5 binding to the MiaPaCa2 “secretome” is sensitive to Proteinase K treatment indicating that the aptamer target is a protein. Currently, we are using a biotinylated version of the aptamer to affinity purify the target and identify it by mass-spectrometric techniques.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2817. doi:10.1158/1538-7445.AM2011-2817

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2011

Volume

71

Issue

8_Supplement

Start / End Page

2817 / 2817

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
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MLA
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Ray, P., Sullenger, B. A., & White, R. R. (2011). Abstract 2817: An RNA aptamer is a potential biomarker for pancreatic cancer. Cancer Research, 71(8_Supplement), 2817–2817. https://doi.org/10.1158/1538-7445.am2011-2817
Ray, Partha, Bruce A. Sullenger, and Rebekah R. White. “Abstract 2817: An RNA aptamer is a potential biomarker for pancreatic cancer.” Cancer Research 71, no. 8_Supplement (April 15, 2011): 2817–2817. https://doi.org/10.1158/1538-7445.am2011-2817.
Ray P, Sullenger BA, White RR. Abstract 2817: An RNA aptamer is a potential biomarker for pancreatic cancer. Cancer Research. 2011 Apr 15;71(8_Supplement):2817–2817.
Ray, Partha, et al. “Abstract 2817: An RNA aptamer is a potential biomarker for pancreatic cancer.” Cancer Research, vol. 71, no. 8_Supplement, American Association for Cancer Research (AACR), Apr. 2011, pp. 2817–2817. Crossref, doi:10.1158/1538-7445.am2011-2817.
Ray P, Sullenger BA, White RR. Abstract 2817: An RNA aptamer is a potential biomarker for pancreatic cancer. Cancer Research. American Association for Cancer Research (AACR); 2011 Apr 15;71(8_Supplement):2817–2817.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2011

Volume

71

Issue

8_Supplement

Start / End Page

2817 / 2817

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis