Casein kinase II alpha subunit and C1-inhibitor are independent predictors of outcome in patients with squamous cell carcinoma of the lung Journal Article
| Authors: | O-Charoenrat, P.; Rusch, V.; Talbot, S. G.; Sarkaria, I.; Viale, A.; Socci, N.; Ngai, I.; Rao, P.; Singh, B. |
| Article Title: | Casein kinase II alpha subunit and C1-inhibitor are independent predictors of outcome in patients with squamous cell carcinoma of the lung |
| Abstract: | Purpose: Gene expression profiling has been shown to be a valuable tool for prognostication and identification of cancer-associated genes in human malignancies. We aimed to identify potential prognostic marker(s) in non-small cell lung cancers using global gene expression profiles. Experimental Design: Twenty-one previously untreated patients with non-small cell lung cancer were analyzed using the Affymetrix GeneChip high-density oligonucleotide array and comparative genomic hybridization. Identified candidate genes were validated in an independent cohort of 45 patients using quantitative real-time reverse transcription-PCR and Western blot analyses. Follow-up data for these patients was collected and used to assess outcome correlations. Results: Hierarchical clustering analysis yielded three distinct subgroups based on gene expression profiling. Cluster I consisted of 4 patients with adenocarcinoma and 1 with squamous cell carcinoma (squamous cell carcinoma); clusters II and III consisted of 6 and 10 patients with squamous cell carcinoma, respectively. Outcome analysis was performed on the cluster groups containing solely squamous cell carcinoma, revealing significant differences in disease-specific survival rates. Moreover, patients having a combination of advanced Tumor-Node-Metastasis stage and assigned to the poor prognosis cluster group (cluster II) had significantly poorer outcomes. Comparative genomic hybridization analysis showed recurrent chromosomal losses at 1p, 3p, 17, 19, and 22 and gains/amplifications at 3q, 5p, and 8q, which did not vary significantly between the cluster groups. We internally and externally validated a subset of 11 cluster II (poor prognosis)-specific genes having corresponding chromosomal aberrations identified by comparative genomic hybridization as prognostic markers in an independent cohort of patients with lung squamous cell carcinoma identifying CSNK2A1 and C1-Inh as independent predictors of outcome. Conclusion: CSNK2A1 and C1-Inh are independent predictors of survival in lung squamous cell carcinoma patients and may be useful as prognostic markers. |
| Keywords: | cancer survival; human tissue; aged; survival rate; unclassified drug; squamous cell carcinoma; carcinoma, squamous cell; cancer patient; follow-up studies; lymph node metastasis; reverse transcription polymerase chain reaction; cohort studies; cluster analysis; gene expression profiling; lung non small cell cancer; lung neoplasms; tumor markers, biological; cohort analysis; cysteine proteinase inhibitors; prediction; chromosome aberration; blotting, western; oligonucleotide array sequence analysis; nucleotide sequence; western blotting; predictive value of tests; outcomes research; lung carcinoma; dna microarray; chromosome aberrations; nucleic acid hybridization; protein subunits; alpha chain; unindexed sequence; chromosome loss; comparative genomic hybridization; casein kinase ii; biochemical marker; humans; prognosis; human; male; female; priority journal; article; casein kinase ii alpha subunit; complement component c1s inhibitor; complement c1 inactivator proteins; complement c1 inhibitor protein |
| Journal Title: | Clinical Cancer Research |
| Volume: | 10 |
| Issue: | 17 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-09-01 |
| Start Page: | 5792 |
| End Page: | 5803 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-03-0317 |
| PROVIDER: | scopus |
| PUBMED: | 15355908 |
| DOI/URL: | |
| Notes: | Clin. Cancer Res. -- Cited By (since 1996):56 -- Export Date: 16 June 2014 -- CODEN: CCREF -- Molecular Sequence Numbers: GENBANK: AB013924, AF000959, AF022991, AF042792, AF047419, AF052124, AF052389, AF060568, AF063002, AF078077, AF091433, AI375913, AL031058, D10667, D49493, J05070, K03515, L06139, L13740, L17131, M18667, M21056, M24430, M32313, M54995, M55265, M55699, M63391, M83670, M87339, M91211, M97252, U12767, U13219, U34846, U39447, U63743, U73379, U89281, U89337, X03350, X53463, X54131, X55550, X58288, X64559, X69490, X77777, X79981, Z46580; -- Source: Scopus |
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