Proteomic profiling of paraffin-embedded samples identifies metaplasia-specific and early-stage gastric cancer biomarkers

Josane F. Sousa, Amy Joan L. Ham, Corbin Whitwell, KiTaek Nam, Hyuk Joon Lee, Han Kwang Yang, Woo Ho Kim, Bing Zhang, Ming Li, Bonnie Lafleur, Daniel C. Liebler, James R. Goldenring

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Early diagnosis and curative resection are the predominant factors associated with increased survival in patients with gastric cancer. However, most gastric cancer cases are still diagnosed at later stages. Since most pathologic specimens are archived as FFPE samples, the ability to use them to generate expression profiles can greatly improve cancer biomarker discovery. We sought to uncover new biomarkers for stomach preneoplastic metaplasias and neoplastic lesions by generating proteome profiles using FFPE samples. We combined peptide isoelectric focusing and liquid chromatography-tandem mass spectrometry analysis to generate proteomic profiles from FFPE samples of intestinal-type gastric cancer, metaplasia, and normal mucosa. The expression patterns of selected proteins were analyzed by immunostaining first in single tissue sections from normal stomach, metaplasia, and gastric cancer and later in larger tissue array cohorts. We detected 60 proteins up-regulated and 87 proteins down-regulated during the progression from normal mucosa to metaplasia to gastric cancer. Two of the up-regulated proteins, LTF and DMBT1, were validated as specific markers for spasmolytic polypeptide-expressing metaplasia and intestinal metaplasia, respectively. In cancers, significantly lower levels of DMBT1 or LTF correlated with more advanced disease and worse prognosis. Thus, proteomic profiling using FFPE samples has led to the identification of two novel markers for stomach metaplasias and gastric cancer prognosis.

Original languageEnglish
Pages (from-to)1560-1572
Number of pages13
JournalAmerican Journal of Pathology
Volume181
Issue number5
DOIs
Publication statusPublished - 2012 Nov 1

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Metaplasia
Tumor Biomarkers
Paraffin
Proteomics
Stomach Neoplasms
Mucous Membrane
Proteins
Intestinal Neoplasms
Isoelectric Focusing
Proteome
Tandem Mass Spectrometry
Liquid Chromatography
Early Diagnosis
Stomach
Biomarkers
Peptides
Survival

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Sousa, Josane F. ; Ham, Amy Joan L. ; Whitwell, Corbin ; Nam, KiTaek ; Lee, Hyuk Joon ; Yang, Han Kwang ; Kim, Woo Ho ; Zhang, Bing ; Li, Ming ; Lafleur, Bonnie ; Liebler, Daniel C. ; Goldenring, James R. / Proteomic profiling of paraffin-embedded samples identifies metaplasia-specific and early-stage gastric cancer biomarkers. In: American Journal of Pathology. 2012 ; Vol. 181, No. 5. pp. 1560-1572.
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Sousa, JF, Ham, AJL, Whitwell, C, Nam, K, Lee, HJ, Yang, HK, Kim, WH, Zhang, B, Li, M, Lafleur, B, Liebler, DC & Goldenring, JR 2012, 'Proteomic profiling of paraffin-embedded samples identifies metaplasia-specific and early-stage gastric cancer biomarkers', American Journal of Pathology, vol. 181, no. 5, pp. 1560-1572. https://doi.org/10.1016/j.ajpath.2012.07.027

Proteomic profiling of paraffin-embedded samples identifies metaplasia-specific and early-stage gastric cancer biomarkers. / Sousa, Josane F.; Ham, Amy Joan L.; Whitwell, Corbin; Nam, KiTaek; Lee, Hyuk Joon; Yang, Han Kwang; Kim, Woo Ho; Zhang, Bing; Li, Ming; Lafleur, Bonnie; Liebler, Daniel C.; Goldenring, James R.

In: American Journal of Pathology, Vol. 181, No. 5, 01.11.2012, p. 1560-1572.

Research output: Contribution to journalArticle

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AU - Goldenring, James R.

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