Showing papers by "Tianwei Yu published in 2008"

Transcriptomic dissection of tongue squamous cell carcinoma

Abstract: The head and neck/oral squamous cell carcinoma (HNOSCC) is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC) is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC. Genome-wide transcriptomic profiles were obtained for 53 primary OTSCCs and 22 matching normal tissues. Genes that exhibit statistically significant differences in expression between OTSCCs and normal were identified. These include up-regulated genes (MMP1, MMP10, MMP3, MMP12, PTHLH, INHBA, LAMC2, IL8, KRT17, COL1A2, IFI6, ISG15, PLAU, GREM1, MMP9, IFI44, CXCL1), and down-regulated genes (KRT4, MAL, CRNN, SCEL, CRISP3, SPINK5, CLCA4, ADH1B, P11, TGM3, RHCG, PPP1R3C, CEACAM7, HPGD, CFD, ABCA8, CLU, CYP3A5). The expressional difference of IL8 and MMP9 were further validated by real-time quantitative RT-PCR and immunohistochemistry. The Gene Ontology analysis suggested a number of altered biological processes in OTSCCs, including enhancements in phosphate transport, collagen catabolism, I-kappaB kinase/NF-kappaB signaling cascade, extracellular matrix organization and biogenesis, chemotaxis, as well as suppressions of superoxide release, hydrogen peroxide metabolism, cellular response to hydrogen peroxide, keratinization, and keratinocyte differentiation in OTSCCs. In summary, our study provided a transcriptomic signature for OTSCC that may lead to a diagnosis or screen tool and provide the foundation for further functional validation of these specific candidate genes for OTSCC.

Proteomic based identification of manganese superoxide dismutase 2 (SOD2) as a metastasis marker for oral squamous cell carcinoma.

Abstract: Metastasis is a critical event in oral squamous cell carcinoma (OSCC) progression. To identify proteomic biomarkers for OSCC metastasis, 3 paired OSCC cell lines (UM1/UM2, 1386Tu/1386Ln, 686Tu/686Ln) with different metastatic potential were examined. Among those 3 cell lines, UM1, 1386Ln and 686Ln exhibited a higher degree of metastatic potential than their paired cell lines UM2, 1386Tu and 686Tu, respectively, as measured using an in vitro cell invasion assay. A total of 40 differentially expressed proteins were identified using 2D-PAGE/MS proteomic approach. Selected protein candidates (superoxide dismutase 2 and heat shock protein 27) were further investigated by immuno- histochemistry (IHC) method using independent OSCC patient tissue samples. The statistically significantly increases in IHC staining for manganese superoxide dismutase 2 (SOD2) were observed in lymph node metastatic disease when compared with the paired primary OSCC. Our results thus indicated that elevated SOD2 levels is associated with lymph node metastasis in OSCC and may provide predictive values for diagnosis of metastasis. Oral cancer, predominantly oral squamous cell carcinoma (OSCC), is one of the most devastating diseases. The American Cancer Society estimated that more than 30,000 new cases of oral cancer were diagnosed in 2006, representing approximately 3% of all malignancies in men and 2% of all malignancies in women. Worldwide oral cancer is a major cancer problem (ranked as the 6th), with an estimated 300,000 new cases diagnosed annually (1, 2). Despite the tremendous improvements in surgery, radio- therapy and chemotherapy over the last decade, the prognosis for patients with OSCC is more or less unchanged for the past 3 decades. This is because patients continue to die from metastatic diseases at regional and distant sites. Improvement in patient survival requires an increased understanding of tumor metastasis so that aggressive tumors can be detected early in the disease process and targeted therapeutic interventions can be developed. Currently, no molecular biomarkers have been included in clinical work-up strategies for the detection of nodal metastasis. Since several genes have been reported in retrospective trials to yield prognostic information independently of the TMN classification, it is reasonable to hypothesize that molecular "fingerprints" could exist that might define sub-groups of patients with significantly more aggressive disease. The tumor cells may progress via the bloodstream or the lymphatics to colonize new areas of the body. The metastasis of the OSCCs is unique in that they metastasize mainly to regional lymph nodes through the draining lymphatics, where metastasis to distant sites is relatively uncommon. Several recent gene expression studies from this and other laboratories have suggested the existence

Dimension reduction and mixed-effects model for microarray meta-analysis of cancer.

Abstract: The rapid advances in high-throughput microarray technologies greatly facilitate the disease biomarker discovery. However, the potential of these microarray data has not yet been fully utilized. This is partly due to the limited sample sizes of each individual study. Combining microarray data from multiple studies improves the statistical power of detecting differentially expressed genes. Here we present a method for combining the microarray datasets at array probeset level. Using datasets from two commonly used array platforms, the Affymetrix Human Genome U133A and Human Genome U133 Plus 2.0 arrays, we found laboratory effects may be more influential than the platform effect. A visualization scheme for merging the array data from different array platforms was proposed to qualitatively judge the degree of agreement between datasets. A mixed-effects model was applied to identify differentially expressed genes from the merged array data.