Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer among men in the developed world. There is a need, for both clinical and scientific reasons, to find markers to identify patients with aggressive disease as early as possible, and to understand the events leading to malignant transformation and susceptibility to metastasis. We report the first large-scale gene expression analysis of a unique HNSCC location, the hypopharynx. Four normal and 34 tumour samples were analysed with 12 600 gene microarrays. Clusters of differentially expressed genes were identified in the chromosomal regions 3q27.3, 17q21.2–q21.31, 7q11.22–q22.1 and 11q13.1–q13.3, which, interestingly, have already been identified by comparative genomic hybridization (CGH) as major regions of gene amplification. We showed that six overexpressed genes (EIF4G1, DVL3, EPHB4, MCM7, BRMS1 and SART1) located in these regions are indeed amplified. We report 119 genes that are highly differentially expressed between ‘early’ tumours and normal samples. Of these, we validated by quantitative PCR six novel poorly characterized genes. These genes are potential new markers of HNSCC. Comparing patients with relatively nonaggressive and aggressive tumours (without or with clinical evidence of metastasis 3 years after surgery), we identified 164 differentially expressed genes potentially involved in the acquisition of metastatic potential. This study contributes to the understanding of HNSCC, staging patients into prognostic groups and identifying high-risk patients who may benefit from more aggressive treatment.

[1]  D. Sivam,et al.  Identification of Genes Overexpressed in Head and Neck Squamous Cell Carcinoma Using a Combination of Complementary DNA Subtraction and Microarray Analysis , 2000, The Laryngoscope.

[2]  R. Todd,et al.  Oral cancer in vivo gene expression profiling assisted by laser capture microdissection and microarray analysis , 2001, Oncogene.

[3]  W. Foulkes,et al.  Identification of genes associated with head and neck carcinogenesis by cDNA microarray comparison between matched primary normal epithelial and squamous carcinoma cells , 2002, Oncogene.

[4]  P. Venugopal,et al.  SCF, IL-1beta, IL-1ra and GM-CSF in the bone marrow and serum of normal individuals and of AML and CML patients. , 2000, Cytokine.

[5]  Michael L. Bittner,et al.  Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[7]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  L. Zhao,et al.  Transcriptional expression profiles of oral squamous cell carcinomas , 2002, Cancer.

[9]  Alejandro A Schäffer,et al.  Genetic differences detected by comparative genomic hybridization in head and neck squamous cell carcinomas from different tumor sites: construction of oncogenetic trees for tumor progression , 2002, Genes, chromosomes & cancer.

[10]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[11]  Robert A. Weinberg,et al.  Metastasis genes: A progression puzzle , 2002, Nature.

[12]  N. Sampas,et al.  Molecular classification of cutaneous malignant melanoma by gene expression profiling , 2000, Nature.

[13]  G. Mills,et al.  Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production , 2002, The Journal of cell biology.

[14]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[15]  S. Gollin Chromosomal alterations in squamous cell carcinomas of the head and neck: Window to the biology of disease , 2001, Head & neck.

[16]  Christian A. Rees,et al.  Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  E. Adashi,et al.  The midcycle increase in ovarian glucose uptake is associated with enhanced expression of glucose transporter 3. Possible role for interleukin-1, a putative intermediary in the ovulatory process. , 1997, The Journal of clinical investigation.

[19]  J. Li,et al.  Reversal effects of nomegestrol acetate on multidrug resistance in adriamycin-resistant MCF7 breast cancer cell line , 2001, Breast Cancer Research.

[20]  E. Lander,et al.  Gene expression correlates of clinical prostate cancer behavior. , 2002, Cancer cell.

[21]  H. Quon,et al.  Potential molecular prognostic markers in head and neck squamous cell carcinomas , 2001, Head and Neck.

[22]  J Silvio Gutkind,et al.  Distinct pattern of expression of differentiation and growth-related genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays , 2000, Oncogene.

[23]  W. Hong,et al.  Differential expression profiling of head and neck squamous carcinoma: significance in their phenotypic and biological classification , 2002, Oncogene.

[24]  R. Tibshirani,et al.  Diagnosis of multiple cancer types by shrunken centroids of gene expression , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[25]  L. Sobin,et al.  TNM classification of malignant tumors, fifth edition (1997) , 1997, Cancer.

[26]  Gideon Rechavi,et al.  A Possible Role for CXCR4 and Its Ligand, the CXC Chemokine Stromal Cell-Derived Factor-1, in the Development of Bone Marrow Metastases in Neuroblastoma1 , 2001, The Journal of Immunology.

[27]  L. Bracco,et al.  Differential expression profiling of head and neck squamous cell carcinoma (HNSCC) , 2003, British Journal of Cancer.

[28]  V. Eijkhout Oral , 2018, Modern Pathology.

[29]  D. Botstein,et al.  Singular value decomposition for genome-wide expression data processing and modeling. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. Botstein,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .