S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer

Sven Diederichs, Etmar Bulk, Björn Steffen, Ping Ji, Lara Tickenbrock, Kerstin Lang, Kurt S. Zänker, Ralf Metzger, Paul M. Schneider, Volker Gerke, Michael Thomas, Wolfgang E. Berdel, Hubert Serve, Carsten Müler-Tidow

Research output: Contribution to journalArticle

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Abstract

Distant metastasis is the predominant cause of death in early-stage non-small cell lung cancer (NSCLC). Currently, it is impossible to predict the occurrence of metastasis at early stages and thereby separate patients who could be cured by surgical resection alone from patients who would benefit from additional chemotherapy. In this study, we applied a comparative microarray approach to identify gene expression differences between early-stage NSCLC patients whose cancer ultimately did or did not metastasize during the course of their disease. Transcriptional profiling of 82 microarrays from two patient groups revealed differential expression of several gene families including known predictors of metastasis (eg., matrix metalloproteinases). In addition, we found S100P, S100A2, trypsinogen C (TRY6), and trypsinogen IVb (PRSS3) to be overexpressed in tumors that metastasized during the course of the disease. In a third group of 42 patients, we confirmed the induction of S100 proteins and trypsinogens in metastasizing tumors and its significant correlation with survival by real-time quantitative reverse transcription. PCR. Overexpression of S100A2, S100P, or PRSS3 in NSCLC cell cultures led to increased transendothelial migration, corroborating the role of S100A2, S100P, and PRSS3 in the metastatic process. Taken together, we provide evidence that expression of S100 proteins and trypsinogens is associated with metastasis and predicts survival in early stages of NSCLC. For the first time, this implicates a role of S100 proteins and trypsinogens in the metastatic process of early-stage NSCLC.

Original languageEnglish (US)
Pages (from-to)5564-5569
Number of pages6
JournalCancer Research
Volume64
Issue number16
DOIs
StatePublished - Aug 15 2004
Externally publishedYes

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Trypsinogen
Non-Small Cell Lung Carcinoma
S100 Proteins
Neoplasm Metastasis
Survival
Transendothelial and Transepithelial Migration
Gene Expression
Neoplasms
Matrix Metalloproteinases
Reverse Transcription
Cause of Death
Cell Culture Techniques
Drug Therapy
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. / Diederichs, Sven; Bulk, Etmar; Steffen, Björn; Ji, Ping; Tickenbrock, Lara; Lang, Kerstin; Zänker, Kurt S.; Metzger, Ralf; Schneider, Paul M.; Gerke, Volker; Thomas, Michael; Berdel, Wolfgang E.; Serve, Hubert; Müler-Tidow, Carsten.

In: Cancer Research, Vol. 64, No. 16, 15.08.2004, p. 5564-5569.

Research output: Contribution to journalArticle

Diederichs, S, Bulk, E, Steffen, B, Ji, P, Tickenbrock, L, Lang, K, Zänker, KS, Metzger, R, Schneider, PM, Gerke, V, Thomas, M, Berdel, WE, Serve, H & Müler-Tidow, C 2004, 'S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer', Cancer Research, vol. 64, no. 16, pp. 5564-5569. https://doi.org/10.1158/0008-5472.CAN-04-2004
Diederichs, Sven ; Bulk, Etmar ; Steffen, Björn ; Ji, Ping ; Tickenbrock, Lara ; Lang, Kerstin ; Zänker, Kurt S. ; Metzger, Ralf ; Schneider, Paul M. ; Gerke, Volker ; Thomas, Michael ; Berdel, Wolfgang E. ; Serve, Hubert ; Müler-Tidow, Carsten. / S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. In: Cancer Research. 2004 ; Vol. 64, No. 16. pp. 5564-5569.
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AU - Diederichs, Sven

AU - Bulk, Etmar

AU - Steffen, Björn

AU - Ji, Ping

AU - Tickenbrock, Lara

AU - Lang, Kerstin

AU - Zänker, Kurt S.

AU - Metzger, Ralf

AU - Schneider, Paul M.

AU - Gerke, Volker

AU - Thomas, Michael

AU - Berdel, Wolfgang E.

AU - Serve, Hubert

AU - Müler-Tidow, Carsten

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N2 - Distant metastasis is the predominant cause of death in early-stage non-small cell lung cancer (NSCLC). Currently, it is impossible to predict the occurrence of metastasis at early stages and thereby separate patients who could be cured by surgical resection alone from patients who would benefit from additional chemotherapy. In this study, we applied a comparative microarray approach to identify gene expression differences between early-stage NSCLC patients whose cancer ultimately did or did not metastasize during the course of their disease. Transcriptional profiling of 82 microarrays from two patient groups revealed differential expression of several gene families including known predictors of metastasis (eg., matrix metalloproteinases). In addition, we found S100P, S100A2, trypsinogen C (TRY6), and trypsinogen IVb (PRSS3) to be overexpressed in tumors that metastasized during the course of the disease. In a third group of 42 patients, we confirmed the induction of S100 proteins and trypsinogens in metastasizing tumors and its significant correlation with survival by real-time quantitative reverse transcription. PCR. Overexpression of S100A2, S100P, or PRSS3 in NSCLC cell cultures led to increased transendothelial migration, corroborating the role of S100A2, S100P, and PRSS3 in the metastatic process. Taken together, we provide evidence that expression of S100 proteins and trypsinogens is associated with metastasis and predicts survival in early stages of NSCLC. For the first time, this implicates a role of S100 proteins and trypsinogens in the metastatic process of early-stage NSCLC.

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