RANTES expression is a predictor of survival in stage I lung adenocarcinoma.

Abstract

PURPOSE:

The presence of an active lymphocytic response (ALR) in non-small cell lung cancer (NSCLC) tumors has previously been associated with a more favorable prognosis. The purpose of this study was to identify differences in global gene expression profiles between stage I NSCLC tumors with ALR (ALR+) and those without ALR (ALR-).

EXPERIMENTAL DESIGN:

Sixty-three stage I lung adenocarcinomas were analyzed for gene expression using Affymetrix oligonucleotide microarrays. Tumors were stratified into ALR+ and ALR- groups and compared for statistically significant differences in gene expression. Identified candidate genes were validated using both ELISA and immunohistochemistry. Follow-up data for these patients were collected and used to assess patient prognosis.

RESULTS:

Of the 63 tumors studied, 27 were ALR+ and 36 were ALR-. A total of 303 genes showed significant differences in gene expression between the two populations (t test, P < 0.02). Three of the genes overexpressed by ALR+ tumors were the chemokines: small inducible cytokine A4 (MIP-1beta), RANTES, and interferon inducible protein 10 (IP-10). Immunohistochemistry analysis showed that the tumor cells expressed these cytokines. ELISA showed that MIP-1beta and RANTES were overexpressed at the protein level by ALR+ tumors. Univariate Cox proportional hazards analysis showed that RANTES was a predictor of survival in stage I lung adenocarcinomas (P = 0.002).

CONCLUSION:

When tested in the Cox univariate proportional hazards model, RANTES expression by lung adenocarcinoma cells is a predictor of survival in stage I NSCLC patients and may be useful as a prognostic factor in lung cancer.

• Authors: Christopher J Moran, Douglas A Arenberg, Chiang-Ching Huang, Thomas J Giordano, Dafydd G Thomas, David E Misek, Guoan Chen, Mark D Iannettoni, Mark B Orringer, Samir Hanash, David G Beer
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 8 Issue 12 Pg. 3803-12 (Dec 2002) ISSN: 1078-0432 [Print] United States
• PMID: 12473593 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chemokine CCL4
• Chemokine CCL5
• Chemokine CXCL10
• Chemokines, CXC
• Macrophage Inflammatory Proteins
• Neoplasm Proteins
• RNA, Messenger
• Interferon-gamma

Topics

• Adenocarcinoma (genetics, metabolism, mortality)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, mortality)
• Chemokine CCL4
• Chemokine CCL5 (genetics, metabolism)
• Chemokine CXCL10
• Chemokines, CXC (genetics, metabolism)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immunoenzyme Techniques
• Interferon-gamma (genetics, metabolism)
• Lung Neoplasms (genetics, metabolism, mortality)
• Lymphocyte Activation
• Macrophage Inflammatory Proteins (genetics, metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Neoplasm Staging
• Oligonucleotide Array Sequence Analysis
• Prognosis
• RNA, Messenger (metabolism)
• Survival Rate