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 diseasespecific 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.

Phosphorylation of basic helix–loop–helix transcription factor Twist in development and disease

“…IL-6 (interleukin 6) levels are increased in SCCHN patients and correlate with a worse clinical outcome. In addition, CK2 is activated in many types of cancer, including SCCHN [26]. In spite of MAPKs (mitogen-activated protein kinases) as the canonical downstream targets of IL-6 signalling, CK2 was reported to be indispensable downstream of IL-6 signalling in a context-dependent manner [27].…”

CX-4945, an Orally Bioavailable Selective Inhibitor of Protein Kinase CK2, Inhibits Prosurvival and Angiogenic Signaling and Exhibits Antitumor Efficacy

“…However, CK2 gene amplifications and an associated reduction in patient survival have been described in squamous cell lung cancer (8). Likewise, CK2 activity and expression levels are elevated in many cancers of diverse genetic background including breast (9), lung (8), prostate (10), colorectal (11), renal (12), and leukemias (13), and the overexpression of CK2 in cancer tissues has frequently been linked to disease progression and poor prognosis (reviewed in refs. 14 and 6).…”

Les polyoxométallates

“…L'expression de CK2 est déré-gulée dans un large panel de cancers et son activité kinase est corrélée à la progression tumorale. Ainsi, des travaux de plusieurs laboratoires, dont le nôtre, ont montré que la surexpression ou la localisation cellulaire aberrante de CK2 constitue un marqueur pronostique défavorable dans les cancers de la prostate [4], du poumon [5] et dans les leucémies aiguës myéloïdes [6]. De plus, des travaux récents ont montré que l'inhibition de CK2 dans un modèle murin de xénogreffe tumorale induit une régres-sion des tumeurs implantées [7], ce qui suggère que cette enzyme exerce, à côté de ses fonctions normales, des fonctions directement associées à l'oncogenèse.…”