Main histologic types of non-small-cell lung cancer differ in expression of prognosis-related genes.

Abstract

BACKGROUND:

There is increasing evidence that suggests that particular histopathologic types of non-small-cell lung cancer (NSCLC) display distinct molecular characteristics. We analyzed, in lung squamous cell carcinoma (SCC) and adenocarcinoma (AC), the expression of 8 genes that constitute 2 previously reported prognostic expression signatures in NSCLC.

METHODS:

Fresh-frozen tumor and normal lung samples were obtained at surgery from 135 patients with stage I-III NSCLC (89 (65.9%) SCC, 46 (34.1%) AC). Expression of CSF1 (colony stimulating factor for macrophages), carbonic anhydrase 9 (CA9), epithelial growth factor receptor (EGFR), dual specificity phosphatase 6 (DUSP6), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3), monocyte to macrophage differentiation-associated (MMD), lymphocyte-specific protein tyrosine kinase (LCK) and signal transducer and activator of transcription 1 (STAT1) was assessed in SCC, AC, and in normal lung by quantitative reverse transcriptase - polymerase chain reaction (qRT-PCR). Metastasis-free survival was analyzed according to the median value of gene expression in the entire NSCLC cohort and separately in SCC and AC.

RESULTS:

Expression of CA9, CSF1, DUSP6, STAT1, and MMD differed between NSCLC and normal lung. EGFR was more abundant in SCC compared with AC, whereas the reverse was true for DUSP6 and ERBB3. A high expression of CSF1 correlated with shorter metastasis-free survival in the entire NSCLC group (P = .016) and in SCC (P = .049) and AC (P = .034) cohorts.

CONCLUSIONS:

Several genes considered prognostic in NSCLC showed significantly different expression in SCC and AC, and thus should be analyzed separately in these 2 subtypes for their prognostic significance. CSF1 is similarly expressed in SCC and AC, and portends a poor outcome in the entire group of patients with NSCLC, and in SCC and AC when considered separately.

• Authors: Marcin Skrzypski, Rafał Dziadziuszko, Ewa Jassem, Amelia Szymanowska-Narloch, Grażyna Gulida, Robert Rzepko, Wojciech Biernat, Miquel Taron, Małgorzata Jelitto-Górska, Tomasz Marjański, Witold Rzyman, Rafael Rosell, Jacek Jassem
• Journal: Clinical lung cancer (Clin Lung Cancer) Vol. 14 Issue 6 Pg. 666-673.e2 (Nov 2013) ISSN: 1938-0690 [Electronic] United States
• PMID: 23870818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• Lymphokines
• STAT1 Transcription Factor
• monocyte-macrophage differentiation factor
• Macrophage Colony-Stimulating Factor
• EGFR protein, human
• ERBB3 protein, human
• ErbB Receptors
• Receptor, ErbB-3
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
• DUSP6 protein, human
• Dual Specificity Phosphatase 6
• CA9 protein, human
• Carbonic Anhydrase IX
• Carbonic Anhydrases

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm (genetics, metabolism)
• Biomarkers, Tumor (metabolism)
• Carbonic Anhydrase IX
• Carbonic Anhydrases (genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (diagnosis, mortality, pathology)
• Disease-Free Survival
• Dual Specificity Phosphatase 6 (genetics, metabolism)
• ErbB Receptors (genetics, metabolism)
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (diagnosis, mortality, pathology)
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck) (genetics, metabolism)
• Lymphokines (genetics, metabolism)
• Macrophage Colony-Stimulating Factor (genetics, metabolism)
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Prognosis
• Receptor, ErbB-3 (genetics, metabolism)
• STAT1 Transcription Factor (genetics, metabolism)