Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiles of head and neck squamous cell carcinoma (HNSCC)

ABSTRACT: Distant metastasis is a major factor associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC), but little is known of its molecular mechanisms. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we identified neurotensin, highly expressed in HNSCCs in comparison with normal tissues, as an invasion-promoting factor in HNSCC by using microarray analysis of clinical samples. Indeed, neurotensin overexpression associated with lymph node metastasis of neck, and tumors exhibiting neurotensin overexpression had a poor distant metastasis-free survival rate. In HNSCC cells which expressed neurotensin receptor 1 (NTSR1), neurotensin promoted cellular invasion, migration, and induction of matrix metalloproteinases transcripts. Disruption of NTSR1 signaling by silencing RNA caused the reversion of the invasion of HNSCC cells. By further microarray analysis using neurotensin-treated cells, neurotensin caused increased expression of genes implicated in tumor progression and metastasis including cell growth, migration, invasion, adhesion, angiogenesis, and apoptosis. Our findings have revealed a critical role of neurotensin/NTSR1 for invasion and migration in the metastatic process of HNSCC. This study raises the possibility that neurotensin/NTSR1 could be used as a possible predictive marker and a molecular therapeutic target in the antimetastatic strategies of HNSCC. Keywords: Identification of a novel therapeutic target for head and neck squamous cell carcinomas A total of 21 primary HNSCC samples were obtained from patients who underwent tumor resection at Chiba University Hospital (Chiba, Japan). 21 samples of normal-appearing mucosa at the margin of the surgical resection several centimeters from the tumor were also collected and designated histologically normal mucosa. 21 HNSCCs and paired normal tissues were used for microarray experiment. The clinicopathological grade was classified according to the criteria of the Japan Society for Head and Neck Cancer. The Ethics Committee of Chiba University approved our study, and informed consent was obtained from all patients for use of their tissue samples and clinical data. Tissue samples were immediately snap frozen in liquid nitrogen and stored at -80Â°C until use.

ORGANISM(S): Homo sapiens

SUBMITTER: Satoya Shimizu

PROVIDER: E-GEOD-9638 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of a novel therapeutic target for head and neck squamous cell carcinomas: a role for the neurotensin-neurotensin receptor 1 oncogenic signaling pathway.

Shimizu Satoya S Tsukada Jun J Sugimoto Takashi T Kikkawa Naoko N Sasaki Keita K Chazono Hideaki H Hanazawa Toyoyuki T Okamoto Yoshitaka Y Seki Naohiko N

International journal of cancer 20081001 8

Distant metastasis is a major factor associated with poor prognosis in head and neck squamous cell carcinomas (HNSCC), but little is known of its molecular mechanisms. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Based on a genome-wide gene expression analysis using clinical specimens of HNSCC, we narrowed our focus to the analysis of the neurotensin (NTS) and neurotensin receptor 1 (NTSR1) oncogenic sig ...[more]

PMID: 18661521

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Project description:Head and neck squamous cell carcinomas (HNSCCs) is the seventh most common solid malignancy in the United States, accounting for more than 47,000 new cancer cases. Surgery of patients clinically diagnosed with lymph node metastasis (N+) also involves neck dissection, which causes disfigurement and pain. However, after histological examination, more than 30% of clinically N+ patients turn out to be metastasis-free (N0). Clinically negative lymph node patients have occult node metastasis in up to 50% of the cases. Within two years of follow-up these patients may or may not develop metastatic disease. On the other hand, around 50% of N0 patients do not have occult node metastasis. Therefore, many N0 patients undergo neck dissection unnecessarily. Due to limitations in detecting lymph node metastasis before surgery, both N+ and N0 patients may receive inappropriate treatment. This indicates that a better understanding of the biology of HNSCC is urgently needed. Despite tumor complexity, many studies have tried unsuccessfully to test single genes to be used as prognostic markers in HNSCC. A group of tumor samples can be characterized in terms of the behavior of modules. These modules include clusters of coexpressed genes, such as genes that belong to the same pathway or functional category. Cancer is a multifaceted phenomenon that involves activation and/or disruption of various cellular processes. Thus, the identification of pathways or group of genes such as those involved in the development of lymph node metastasis and recurrent disease may help understanding the complex biology of cancer. Samples were obtained during surgery and neck dissection of 81 patients with primary untreated HNSCC at the Head and Neck Surgery Department from the Hospital AC Camargo (São Paulo, Brazil) between 1998 and 2003. Diagnosis of HNSCC was determined by biopsy. All patients signed a pre-informed consent and the study was approved by our institutional review board. After surgery, all patients were treated with adjuvant radiotherapy. Tumor samples were snap-frozen in liquid nitrogen. Before RNA extraction, diagnosis was confirmed by hematoxylin-eosin staining. Frozen samples were hand dissected for removal of normal cells, necrosis, and infiltrating inflammatory cells. Total RNA was extracted using TRIzol. RNA quality was accessed by spectrophotometry and gel electrophoresis. To be considered as high-quality, the RNA had to have a 260/280 ratio higher than 1.7 and a 18S/28S rRNA ratio ~2. Amplifictaion of the mRNA was done using a T7-based protocol and cDNA was indirectly labeled with Alexa Dye 555 or 647. Samples and a common RNA reference were hybridized overnight at 42oC in dye-swap to a 4,800-element in-house printed microarray, enriched with cancer-related ESTs derived from the Human Cancer Genome Project. After washing, slides were scanned on a confocal laser scanner and data were extracted.

Dataset Information

Gene expression profiles of head and neck squamous cell carcinoma (HNSCC)

Publications

Identification of a novel therapeutic target for head and neck squamous cell carcinomas: a role for the neurotensin-neurotensin receptor 1 oncogenic signaling pathway.

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